Journal of Microbiology

Journal Articles

Characterization of Newly Isolated Bacteriophages Targeting Carbapenem-Resistant Klebsiella pneumoniae: Bokyung Kim, Shukho Kim, Yoon-Jung Choi, Minsang Shin, Jungmin Kim; J. Microbiol. 2024;62(12):1133-1153. Published online December 10, 2024; DOI: https://doi.org/10.1007/s12275-024-00180-7

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Abstract: Klebsiella pneumoniae, a Gram-negative opportunistic pathogen, is increasingly resistant to carbapenems in clinical settings. This growing problem necessitates the development of alternative antibiotics, with phage therapy being one promising option. In this study, we investigated novel phages targeting carbapenem-resistant Klebsiella pneumoniae (CRKP) and evaluated their lytic capacity against clinical isolates of CRKP. First, 23 CRKP clinical isolates were characterized using Multi-Locus Sequence Typing (MLST), carbapenemase test, string test, and capsule typing. MLST classified the 23 K. pneumoniae isolates into 10 sequence types (STs), with the capsule types divided into nine known and one unknown type. From sewage samples collected from a tertiary hospital, 38 phages were isolated. Phenotypic and genotypic characterization of these phages was performed using Random Amplification of Polymorphic DNA-PCR (RAPD-PCR), transmission electron microscopy (TEM), and whole genome sequencing (WGS) analysis. Host spectrum analysis revealed that each phage selectively lysed strains sharing the same STs as their hosts, indicating ST-specific activity. These phages were subtyped based on their host spectrum and RAPD-PCR, identifying nine and five groups, respectively. Fourteen phages were selected for further analysis using TEM and WGS, revealing 13 Myoviruses and one Podovirus. Genomic analysis grouped the phages into three clusters: one closely related to Alcyoneusvirus, one to Autographiviridae, and others to Straboviridae. Our results showed that the host spectrum of K. pneumoniae-specific phages corresponds to the STs of the host strain. These 14 novel phages also hold promise as valuable resources for phage therapy against CRKP.

NEDD4 Regulated Pyroptosis Occurred from Co‑infection between Influenza A Virus and Streptococcus pneumoniae: Jiangzhou You , Linlin Zhou , Xudong San , Hailing Li , Mingyuan Li , Baoning Wang; J. Microbiol. 2023;61(8):777-789. Published online October 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00076-y

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Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and Streptococcus pneumoniae.

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Yinqin Qingfei granules alleviate Mycoplasma pneumoniae pneumonia via inhibiting NLRP3 inflammasome-mediated macrophage pyroptosis
Zhe Song, Chengen Han, Guangzhi Luo, Guangyuan Jia, Xiao Wang, Baoqing Zhang
Frontiers in Pharmacology.2024;[Epub] CrossRef
Overexpression of DTX1 inhibits D-GalN/TNF-α-induced pyroptosis and inflammation in hepatocytes by regulating NLRP3 ubiquitination
Mingshui Liu, Jing Gu, Li Chen, Wei Sun, Xiaoping Huang, Jianhe Gan
Toxicology Research.2024;[Epub] CrossRef
NLRP3 Inflammasomes: Dual Function in Infectious Diseases
Yanbo Li, Rui Qiang, Zhengmin Cao, Qingjuan Wu, Jiuchong Wang, Wenliang Lyu
The Journal of Immunology.2024; 213(4): 407. CrossRef

Varicella‑Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon‑Beta Promoter Activation by Interacting with STING: Gwang Myeong Lee , Shuang Gong , Seong&# , Hyemin Ko , Woo&# , Jihyun Lee , Ok Sarah Shin , Jin&#; J. Microbiol. 2023;61(2):259-270. Published online February 20, 2023; DOI: https://doi.org/10.1007/s12275-023-00019-7

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Abstract: Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-β promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-β production by interacting with STING. In IFN-β promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-β promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-β activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STINGmediated activation of the IFN-β promoter.

Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense: Syahriel Abdullah , Yoon Sin Oh , Min-Kyu Kwak , KhimPhin Chong; J. Microbiol. 2021;59(2):164-174. Published online December 23, 2020; DOI: https://doi.org/10.1007/s12275-021-0551-8

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Abstract

There have been relatively few studies which support a link between Ganoderma boninense, a phytopathogenic fungus that is particularly cytotoxic and pathogenic to plant tissues and roots, and antimicrobial compounds. We previously observed that liquid-liquid extraction (LLE) using chloroformmethanol- water at a ratio (1:1:1) was superior at detecting antibacterial activities and significant quantities of antibacterial compounds. Herein, we demonstrate that antibacterial secondary metabolites are produced from G. boninense mycelia. Antibacterial compounds were monitored in concurrent biochemical and biophysical experiments. The combined
methods
included high performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. The antibacterial compounds derived from mycelia with chloroform-methanol extraction through LLE were isolated via a gradient solvent elution system using HPTLC. The antibacterial activity of the isolated compounds was observed to be the most potent against Staphylococcus aureus ATCC 25923 and multidrug-resistant S. aureus NCTC 11939. GC-MS, HPLC, and FTIR analysis confirmed two antibacterial compounds, which were identified as 4,4,14α-trimethylcholestane (m/z = 414.75; lanostane, C30H54) and ergosta-5,7,22-trien-3β-ol (m/z = 396.65; ergosterol, C28H44O). With the aid of spectroscopic evaluations, ganoboninketal (m/z = 498.66, C30H42O6), which belongs to the 3,4-seco-27-norlanostane triterpene family, was additionally characterized by 2D-NMR analysis. Despite the lack of antibacterial potential exhibited by lanostane; both ergosterol and ganoboninketal displayed significant antibacterial activities against bacterial pathogens. Results provide evidence for the existence of bioactive compounds in the mycelia of the relatively unexplored phytopathogenic G. boninense, together with a robust method for estimating the corresponding potent antibacterial secondary metabolites.

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Anti-Staphylococcus aureus potential of compounds from Ganoderma sp.: A comprehensive molecular docking and simulation approaches
Trang Thi Thu Nguyen, Trinh Thi Tuyet Nguyen, Hoang Duc Nguyen, Tan Khanh Nguyen, Phu Tran Vinh Pham, Linh Thuy Thi Tran, Hong Khuyen Thi Pham, Phu Chi Hieu Truong, Linh Thuoc Tran, Manh Hung Tran
Heliyon.2024; 10(7): e28118. CrossRef
Medium composition optimization and characterization of polysaccharides extracted from Ganoderma boninense along with antioxidant activity
Qian-Zhu Li, Chuan Xiong, Wei Chee Wong, Li-Wei Zhou
International Journal of Biological Macromolecules.2024; 260: 129528. CrossRef
Plant Defense Inducers and Antioxidant Metabolites Produced During Oil Palm-Ganoderma boninense Interaction In Vitro
Neda Shokrollahi, Chai-Ling Ho, Nur Ain Izzati Mohd Zainudin, Mohd As’wad Bin Abdul Wahab, Mui-Yun Wong
Chemistry Africa.2023; 6(1): 499. CrossRef
Identification of Antibacterial Metabolites from Endophytic Fungus Aspergillus fumigatus, Isolated from Albizia lucidior Leaves (Fabaceae), Utilizing Metabolomic and Molecular Docking Techniques
Mai E. Hussein, Osama G. Mohamed, Ahlam M. El-Fishawy, Hesham I. El-Askary, Amira S. El-Senousy, Ahmed A. El-Beih, Eman S. Nossier, Ahmed M. Naglah, Abdulrahman A. Almehizia, Ashootosh Tripathi, Ahmed A. Hamed
Molecules.2022; 27(3): 1117. CrossRef
Bioactive Compounds of Ganoderma boninense Inhibited Methicillin-Resistant Staphylococcus aureus Growth by Affecting Their Cell Membrane Permeability and Integrity
Yow-San Chan, Khim-Phin Chong
Molecules.2022; 27(3): 838. CrossRef
Review Update on the Life Cycle, Plant–Microbe Interaction, Genomics, Detection and Control Strategies of the Oil Palm Pathogen Ganoderma boninense
Izwan Bharudin, Anis Farhan Fatimi Ab Wahab, Muhammad Asyraff Abd Samad, Ng Xin Yie, Madihah Ahmad Zairun, Farah Diba Abu Bakar, Abdul Munir Abdul Murad
Biology.2022; 11(2): 251. CrossRef
Screening for Antibacterial Activity of French Mushrooms against Pathogenic and Multidrug Resistant Bacteria
Clément Huguet, Mélanie Bourjot, Jean-Michel Bellanger, Gilles Prévost, Aurélie Urbain
Applied Sciences.2022; 12(10): 5229. CrossRef

Review

Recent advances in the development of β-lactamase inhibitors: Shivakumar S. Jalde , Hyun Kyung Choi; J. Microbiol. 2020;58(8):633-647. Published online July 27, 2020; DOI: https://doi.org/10.1007/s12275-020-0285-z

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Abstract

β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.

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Functional and structural analyses of IMP-27 metallo-β-lactamase: evolution of IMP-type enzymes to overcome Zn(II) deprivation
Yoshiki Kato, Toshio Yamaguchi, Haruka Nakagawa-Kamura, Yoshikazu Ishii, Akiko Shimizu-Ibuka, Pablo Power
Microbiology Spectrum.2024;[Epub] CrossRef
Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors
Jessica L. Ortega-Balleza, Lenci K. Vázquez-Jiménez, Eyra Ortiz-Pérez, Guadalupe Avalos-Navarro, Alma D. Paz-González, Edgar E. Lara-Ramírez, Gildardo Rivera
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Understanding the Functional Dynamics of the TokK Enzyme in Carbapenem Biosynthesis via MD Simulations and QM/MM Calculations
Shakir Ali Siddiqui, Kshatresh Dutta Dubey
Inorganic Chemistry.2024; 63(40): 18963. CrossRef
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Hao Chang, Renzhong Qiao, Chao Li
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Ying Luo, Taha Majid Mahmood Sheikh, Xin Li, YuMeng Yuan, Fen Yao, Meimei Wang, Xiaoling Guo, Jilong Wu, Muhammad Shafiq, Qingdong Xie, Xiaoyang Jiao
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Decrypting biocontrol functions and application modes by genomes data of three Trichoderma Strains/Species
Shida Ji, Bin Liu, Jing Han, Ning Kong, Yongfeng Yang, Yucheng Wang, Zhihua Liu
Fungal Genetics and Biology.2024; 172: 103889. CrossRef
Revisiting the Checkerboard to Inform Development of β-Lactam/β-Lactamase Inhibitor Combinations
Darren J. Bentley
Antibiotics.2024; 13(4): 337. CrossRef
Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria
Song Zhang, Xinyu Liao, Tian Ding, Juhee Ahn
Antibiotics.2024; 13(3): 260. CrossRef
The C5α-Methyl-Substituted Carbapenem NA-1-157 Exhibits Potent Activity against Klebsiella spp. Isolates Producing OXA-48-Type Carbapenemases
Clyde A. Smith, Nichole K. Stewart, Marta Toth, Pojun Quan, John D. Buynak, Sergei B. Vakulenko
ACS Infectious Diseases.2023; 9(5): 1123. CrossRef
Phenotypes, genotypes and breakpoints: an assessment of β-lactam/β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2023; 78(3): 636. CrossRef
Characteristics of Extended-Spectrum β-Lactamase-Producing Escherichia coli Derived from Food and Humans in Northern Xinjiang, China
Yushuang Wu, Shudi Huang, Donglai Zhang, Hua Ji, Yongqing Ni, Xueling Zhang, Juan Dong, Baokun Li
Foodborne Pathogens and Disease.2023; 20(7): 270. CrossRef
Sequential C−H Methylation Catalyzed by the B12‐Dependent SAM Enzyme TokK: Comprehensive Theoretical Study of Selectivities
Wen‐Hao Deng, Rong‐Zhen Liao
Chemistry – A European Journal.2023;[Epub] CrossRef
CMOS Spectrophotometric Microsystem for Malaria Detection
Gabriel M. Ferreira, Vitória Baptista, Vítor Silva, Maria I. Veiga, Graça Minas, Susana O. Catarino
IEEE Transactions on Biomedical Engineering.2023; 70(8): 2318. CrossRef
Synthesis and β-Lactamase Inhibition Activity of Imidates of Diazabicyclooctane
Lijuan Zhai, Jian Sun, Jingwen Ji, Lili He, Yuanyu Gao, Jinbo Ji, Yuanbai Liu, Yangxiu Mu, Xueqin Ma, Dong Tang, Haikang Yang, Zafar Iqbal, Zhixiang Yang
Russian Journal of Bioorganic Chemistry.2022; 48(5): 1059. CrossRef
Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition
Zafar Iqbal, Jian Sun, Haikang Yang, Jingwen Ji, Lili He, Lijuan Zhai, Jinbo Ji, Pengjuan Zhou, Dong Tang, Yangxiu Mu, Lin Wang, Zhixiang Yang
Molecules.2022; 27(12): 3832. CrossRef
Retracted and replaced: Phenotypes, genotypes and breakpoints: an assessment of β-lactam/ β-lactamase inhibitor combinations against OXA-48
Tomefa E Asempa, Abigail K Kois, Christian M Gill, David P Nicolau
Journal of Antimicrobial Chemotherapy.2022; 77(10): 2622. CrossRef
Carbapenemase producing Klebsiella pneumoniae: implication on future therapeutic strategies
Ilias Karaiskos, Irene Galani, Vassiliki Papoutsaki, Lamprini Galani, Helen Giamarellou
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Raha Orfali, Shagufta Perveen, Mohamed Fahad AlAjmI, Safina Ghaffar, Md Tabish Rehman, Abdullah R. AlanzI, Saja Bane Gamea, Mona Essa Khwayri
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International Journal of Molecular Sciences.2021; 22(2): 617. CrossRef
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In Crystallo Time-Resolved Interaction of the Clostridioides difficile CDD-1 enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D β-lactamases
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ACS Infectious Diseases.2021; 7(6): 1765. CrossRef
Inhibition of the Clostridioides difficile Class D β-Lactamase CDD-1 by Avibactam
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Journal Article

Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling: Ling Wang , Xuemei Zhang , Guangying Wu , Yuhong Qi , Jinghui Zhang , Jing Yang , Hong Wang , Wenchun Xu; J. Microbiol. 2020;58(4):330-339. Published online February 27, 2020; DOI: https://doi.org/10.1007/s12275-020-9538-0

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Abstract

Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

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Maternal immune activation mediated prenatal chronic stress induces Th17/Treg cell imbalance may relate to the PI3K/Akt/NF-κB signaling pathway in offspring rats
Ye Li, Guixiang Yao, Rui Wang, Jiashu Zhu, Hongyu Li, Deguang Yang, Shuqin Ma, Youjuan Fu, Can Liu, Suzhen Guan
International Immunopharmacology.2024; 126: 111308. CrossRef
Secreted protein NFA47630 from Nocardia farcinica IFM10152 induces immunoprotective effects in mice
Lichao Han, Xingzhao Ji, Shihong Fan, Jirao Shen, Bin Liang, Zhenjun Li
Tropical Diseases, Travel Medicine and Vaccines.2024;[Epub] CrossRef
Human microbiomes in cancer development and therapy
Chenglai Xia, Jiyan Su, Can Liu, Zhikai Mai, Shuanghong Yin, Chuansheng Yang, Liwu Fu
MedComm.2023;[Epub] CrossRef
Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis
Yanan He, Jixin Li, Yanjun Qu, Liyuan Sun, Xibo Zhao, Han Wu, Guangmei Zhang, Amar Singh
Journal of Immunology Research.2023; 2023: 1. CrossRef
The identification of two M20B family peptidases required for full virulence in Staphylococcus aureus
Nathanial J. Torres, Devon N. Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey N. Shaw
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Exploration of immune response mechanisms in cadmium and copper co-exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling
Xiaokai Bao, Weijun Wang, Xipan Chen, Yanwei Feng, Xiaohui Xu, Guohua Sun, Bin Li, Xiumei Liu, Zan Li, Jianmin Yang
Frontiers in Immunology.2022;[Epub] CrossRef
Pathogenicity and virulence ofStreptococcus pneumoniae: Cutting to the chase on proteases
Mary E. Marquart
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Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics
Chang Yi Shi, Chen Huan Yu, Wen Ying Yu, Hua Zhong Ying, Hua Zhang
Canadian Journal of Infectious Diseases and Medical Microbiology.2021; 2021: 1. CrossRef

Review

REVIEW] Antibiotic-resistant clones in Gram-negative pathogens: presence of global clones in Korea: Kwan Soo Ko; J. Microbiol. 2019;57(3):195-202. Published online October 2, 2018; DOI: https://doi.org/10.1007/s12275-019-8491-2

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Abstract

Antibiotic resistance is a global concern in public health. Antibiotic-resistant clones can spread nationally, internationally, and globally. This review considers representative antibiotic-resistant Gram-negative bacterial clones–CTX-M- 15-producing ST131 in Escherichia coli, extended-spectrum β-lactamase-producing ST11 and KPC-producing ST258 in Klebsiella pneumoniae, IMP-6-producing, carbapenem-resistant ST235 in Pseudomonas aeruginosa, and OXA-23- producing global clone 2 in Acinetobacter baumannii–that have disseminated worldwide, including in Korea. The findings highlight the urgency for systematic monitoring and international cooperation to suppress the emergence and propagation of antibiotic resistance.

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Molecular epidemiology of carbapenem-resistant gram-negative bacilli in Ecuador
Claudia Soria-Segarra, Carmen Soria-Segarra, Marcos Molina-Matute, Ivanna Agreda-Orellana, Tamara Núñez-Quezada, Kerly Cevallos-Apolo, Marcela Miranda-Ayala, Grace Salazar-Tamayo, Margarita Galarza-Herrera, Victor Vega-Hall, José E. Villacis, José Gutiérr
BMC Infectious Diseases.2024;[Epub] CrossRef
Epidemiological and Molecular Characteristics of blaNDM-1 and blaKPC-2 Co-Occurrence Carbapenem-Resistant Klebsiella pneumoniae
Fang Rong, Ziyi Liu, Pengbin Yang, Feng Wu, Yu Sun, Xuewei Sun, Jun Zhou
Infection and Drug Resistance.2023; Volume 16: 2247. CrossRef
Gold nanoparticle-DNA aptamer-assisted delivery of antimicrobial peptide effectively inhibits Acinetobacter baumannii infection in mice
Jaeyeong Park, Eunkyoung Shin, Ji-Hyun Yeom, Younkyung Choi, Minju Joo, Minho Lee, Je Hyeong Kim, Jeehyeon Bae, Kangseok Lee
Journal of Microbiology.2022; 60(1): 128. CrossRef
Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea
Tae Hee Lee, Minhyeon Cho, Jaehyeon Lee, Joo-Hee Hwang, Chang-Seop Lee, Kyung Min Chung
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Transmission Dynamics of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Strains Carrying Capsular Loci KL64 and rmpA/rmpA2 Genes
Yingying Kong, Qingyang Sun, Hangfei Chen, Mohamed S. Draz, Xinyou Xie, Jun Zhang, Zhi Ruan
Frontiers in Microbiology.2021;[Epub] CrossRef
Microbiota of the lower respiratory tract in community-acquired pneumonia, including cases associated with SARS-CoV-2
L. V. Kataeva, A. A. Vakarina, T. F. Stepanova, K. B. Stepanova
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Journal Articles

Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine: Min Yong Jwa , Soyoung Jeong , Eun Byeol Ko , A Reum Kim , Hyun Young Kim , Sun Kyung Kim , Ho Seong Seo , Cheol-Heui Yun , Seung Hyun Han; J. Microbiol. 2018;56(8):579-585. Published online July 25, 2018; DOI: https://doi.org/10.1007/s12275-018-8347-1

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Abstract

Streptococcus pneumoniae is a major respiratory pathogen that causes millions of deaths worldwide. Although subunit vaccines formulated with the capsular polysaccharides or their protein conjugates are currently-available, low-cost vaccines with wide serotype coverage still remain to be developed, especially for developing countries. Recently, gamma- irradiation has been considered as an effective inactivation
method
to prepare S. pneumoniae vaccine candidate. In this study, we investigated the immunogenicity and protective immunity of gamma-irradiated S. pneumoniae (r-SP), by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP), both of which were made by traditional inactivation methods. Intranasal immunization of C57BL/6 mice with r-SP in combination with cholera toxin as an adjuvant enhanced S. pneumoniaespecific antibodies on the airway mucosal surface and in sera more potently than that with h-SP or f-SP under the same conditions. In addition, sera from mice immunized with r- SP potently induced opsonophagocytic killing activity more effectively than those of h-SP or f-SP, implying that r-SP could induce protective antibodies. Above all, immunization with r-SP effectively protected mice against S. pneumoniae infection. Collectively, these results suggest that gamma- irradiation is an effective method for the development of a killed whole cell pneumococcal vaccine that elicits robust mucosal and systemic immune responses.

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Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine
Julia Finkensieper, Leila Issmail, Jasmin Fertey, Alexandra Rockstroh, Simone Schopf, Bastian Standfest, Martin Thoma, Thomas Grunwald, Sebastian Ulbert
Frontiers in Immunology.2022;[Epub] CrossRef
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Pedro H. Silva, Yaneisi Vázquez, Camilo Campusano, Angello Retamal-Díaz, Margarita K. Lay, Christian A. Muñoz, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
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A Nonadjuvanted Whole-Inactivated Pneumococcal Vaccine Induces Multiserotype Opsonophagocytic Responses Mediated by Noncapsule-Specific Antibodies
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Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine
Eunbyeol Ko, Soyoung Jeong, Min Yong Jwa, A Reum Kim, Ye-Eun Ha, Sun Kyung Kim, Sungho Jeong, Ki Bum Ahn, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
Vaccines.2021; 9(4): 405. CrossRef
Controlling the Colonization of Clostridium perfringens in Broiler Chickens by an Electron-Beam-Killed Vaccine
Palmy R. Jesudhasan, Sohini S. Bhatia, Kirthiram K. Sivakumar, Chandni Praveen, Kenneth J. Genovese, Haiqi L. He, Robert Droleskey, Jack L. McReynolds, James A. Byrd, Christina L. Swaggerty, Michael H. Kogut, David J. Nisbet, Suresh D. Pillai
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Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities
Jasmin Fertey, Martin Thoma, Jana Beckmann, Lea Bayer, Julia Finkensieper, Susann Reißhauer, Beatrice Sarah Berneck, Leila Issmail, Jessy Schönfelder, Javier Portillo Casado, Andre Poremba, Frank-Holm Rögner, Bastian Standfest, Gustavo R. Makert, Lia Walc
Scientific Reports.2020;[Epub] CrossRef
Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection
Catherine B. Blackwood, Emel Sen-Kilic, Dylan T. Boehm, Jesse M. Hall, Melinda E. Varney, Ting Y. Wong, Shelby D. Bradford, Justin R. Bevere, William T. Witt, F. Heath Damron, Mariette Barbier
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Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy
Jasmin Fertey, Lea Bayer, Sophie Kähl, Rukiya M. Haji, Anke Burger-Kentischer, Martin Thoma, Bastian Standfest, Jessy Schönfelder, Javier Portillo Casado, Frank-Holm Rögner, Christoph Georg Baums, Thomas Grunwald, Sebastian Ulbert
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Next-Generation Whole-Cell Pneumococcal Vaccine
Victor Morais, Esther Texeira, Norma Suarez
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Gamma-irradiation-killed Streptococcus pneumoniae potently induces the expression of IL-6 and IL-8 in human bronchial epithelial cells
Min Yong Jwa, Eun Byeol Ko, Hyun Young Kim, Sun Kyung Kim, Soyoung Jeong, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
Microbial Pathogenesis.2018; 124: 38. CrossRef

Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice: Yulan Qiu , Xuemei Zhang , Xinyuan Zhang , Yunjun Mo , Xiaoyu Sun , Jichao Wang , Yibing Yin , Wenchun Xu; J. Microbiol. 2017;55(10):823-829. Published online September 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7262-1

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Abstract

diseases in children under 5-year-old. Vaccine has been used as an indispensable strategy to prevent S. pneumoniae infection for more than 30 years. Our previous studies confirmed that mucosal immunization with live attenuated strain SPY1 can protect mice against nasopharyngeal colonization of S. pneumoniae and lethal pneumococcal infection, and the protective effects are comparable with those induced by commercially available 23-valent polysaccharide vaccine. However, live attenuated vaccine SPY1 needs four inoculations to get satisfactory protective effect, which may increase the risk of virulence recovery. It is reported that heterologous primeboost approach is more effective than homologous primeboost approach. In the present study, to decrease the doses of live SPY1 and improve the safety of SPY1 vaccine, we immunized mice with SPY1 and DnaJ protein alternately. Our
results
showed that heterologous prime-boost immunization with SPY1 and DnaJ protein could significantly reduce the colonization of S. pneumoniae in the respiratory tract of mice, and induce stronger Th1 and Th17 cellular immune responses than SPY1 alone. These results indicate heterologous prime-boost immunization method not only elicits better protective effect than SPY1 alone, but also reduces the doses of live SPY1 and decreases the risk of SPY1 vaccine. This work is the first time to study the protective efficiency with two different forms of S. pneumoniae candidate vaccine, and provides a new strategy for the development of S. pneumoniae vaccine.

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Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection
Yao Wang, Lingyin Xia, Guangli Wang, Huifang Lu, Hui Wang, Shilu Luo, Tao Zhang, Song Gao, Jian Huang, Xun Min
Microbial Pathogenesis.2022; 162: 105325. CrossRef
The imbalance of the Th17/Treg axis following equine ascending placental infection
C.E Fedorka, H. El-Sheikh Ali, O.F. Walker, K.E. Scoggin, P. Dini, S.C. Loux, M.H.T. Troedsson, B.A. Ball
Journal of Reproductive Immunology.2021; 144: 103268. CrossRef
Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections
Yue Zhang, Xiaonan Guo, Mengze Guo, Xiaorui Chen, Bo Li, Jinfei Yu, Tiejun Gu, Wei Kong, Yongge Wu
Immunologic Research.2019; 67(4-5): 398. CrossRef
Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-β1-Smad2/3 Pathway
Hongyi Liao, Xiaoqiong Peng, Lingling Gan, Jiafu Feng, Yue Gao, Shenghui Yang, Xuexue Hu, Liping Zhang, Yibing Yin, Hong Wang, Xiuyu Xu
Frontiers in Immunology.2018;[Epub] CrossRef

Research Support, Non-U.S. Gov'ts

Pneumococcal wall teichoic acid is required for the pathogenesis of Streptococcus pneumoniae in murine models: Hongmei Xu , Libin Wang , Jian Huang , Yanqing Zhang , Feng Ma , Jianmin Wang , Wenchun Xu , Xuemei Zhang , Yibing Yin , Kaifeng Wu; J. Microbiol. 2015;53(2):147-154. Published online January 28, 2015; DOI: https://doi.org/10.1007/s12275-015-4616-4

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Abstract

Pneumococcal asymptomatic colonization of the respiratory tracts is a major risk for invasive pneumococcal disease. We have previously shown that pneumococcal wall teichoic acid (WTA) was involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. In this study, we investigated the contribution of pneumococcal WTA to bacterial colonization and dissemination in murine models. The result showed that nasopharynx colonizing D39 bacterial cells have a distinct phenotype showing an increased exposure of teichoic acids relative to medium-grown bacteria. The WTA-deficient mutants were impaired in their colonization to the nasopharynx and lungs, and led to a mild inflammation in the lungs at 36 h post-inoculation. Pretreatment of the murine nares with WTA reduced the ability of wild type D39 bacteria to colonize the nasopharynx. In addition, the WTA-deficient strain was impaired in its ability to invade the blood and brain following intranasal administration. WTA-deficient D39 strain was reduced in C3 deposition but was more susceptible to the killing by the neutrophils as compared with its parent strain. Our results also demonstrated that the WTA enhanced pneumococcal colonization and dissemination independently of the host strains. These results indicate that WTA plays an important role in pneumococcal pathogenesis, both in colonization and dissemination processes.

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Insight into the structure, biosynthesis, isolation method and biological function of teichoic acid in different gram-positive microorganisms: A review
Jiarun Han, Xin Zhao, Xilian Zhao, Ping Li, Qing Gu
International Journal of Biological Macromolecules.2023; 253: 126825. CrossRef
spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection
Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
Canadian Journal of Microbiology.2018; 64(6): 401. CrossRef
Lipoteichoic acid deficiency permits normal growth but impairs virulence of Streptococcus pneumoniae
Nathalie Heß, Franziska Waldow, Thomas P. Kohler, Manfred Rohde, Bernd Kreikemeyer, Alejandro Gómez-Mejia, Torsten Hain, Dominik Schwudke, Waldemar Vollmer, Sven Hammerschmidt, Nicolas Gisch
Nature Communications.2017;[Epub] CrossRef
New chemical tools to probe cell wall biosynthesis in bacteria
Robert T Gale, Eric D Brown
Current Opinion in Microbiology.2015; 27: 69. CrossRef

Changes in Gene Expression of Actinobacillus pleuropneumoniae in Response to Anaerobic Stress Reveal Induction of Central Metabolism and Biofilm Formation: Lu Li , Jiawen Zhu , Kui Yang , Zhuofei Xu , Ziduo Liu , Rui Zhou; J. Microbiol. 2014;52(6):473-481. Published online April 11, 2014; DOI: https://doi.org/10.1007/s12275-014-3456-y

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Abstract

Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry worldwide. Oxygen deprivation is a stress that A. pleuropneumoniae will encounter during both early infection and the later, persistent stage. To understand modulation of A. pleuropneumoniae gene expression in response to the stress caused by anaerobic conditions, gene expression profiles under anaerobic and aerobic conditions were compared in this study. The microarray results showed that 631 genes (27.7% of the total ORFs) were differentially expressed in anaerobic conditions. Many genes encoding proteins involved in glycolysis, carbon source uptake systems, pyruvate metabolism, fermentation and the electron respiration transport chain were up-regulated. These changes led to an increased amount of pyruvate, lactate, ethanol and acetate in the bacterial cells as confirmed by metabolite detection. Genes encoding proteins involved in cell surface structures, especially biofilm formation, peptidoglycan biosynthesis and lipopolysaccharide biosynthesis were up-regulated as well. Biofilm formation was significantly enhanced under anaerobic conditions. These results indicate that induction of central metabolism is important for basic survival of A. pleuropneumoniae after a shift to an anaerobic environment. Enhanced biofilm formation may contribute to the persistence of this pathogen in the damaged anaerobic host tissue and also in the early colonization stage. These discoveries give new insights into adaptation mechanisms of A. pleuropneumoniae in response to environmental stress.

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Mycobacteroides abscessus ability to interact with the host mucosal cells plays an important role in pathogenesis of the infection
Amy Leestemaker-Palmer, Luiz E. Bermudez
Critical Reviews in Microbiology.2024; : 1. CrossRef
The morphology and metabolic changes of Actinobacillus pleuropneumoniae during its growth as a biofilm
Qiuhong Zhang, Lu Peng, Weiyao Han, Hongyu Chen, Hao Tang, Xiabing Chen, Paul R. Langford, Qi Huang, Rui Zhou, Lu Li
Veterinary Research.2023;[Epub] CrossRef
The Metabolic Adaptation in Response to Nitrate Is Critical for Actinobacillus pleuropneumoniae Growth and Pathogenicity under the Regulation of NarQ/P
Qiuhong Zhang, Hao Tang, Chaoyue Yan, Weiyao Han, Lu Peng, Jiajia Xu, Xiabing Chen, Paul R. Langford, Weicheng Bei, Qi Huang, Rui Zhou, Lu Li, Andreas J. Bäumler
Infection and Immunity.2022;[Epub] CrossRef
Identification of FtpA, a Dps-Like Protein Involved in Anti-Oxidative Stress and Virulence in Actinobacillus pleuropneumoniae
Hao Tang, Qiuhong Zhang, Weiyao Han, Zhenyue Wang, Siqi Pang, Han Zhu, Kangning Tan, Xiao Liu, Paul R. Langford, Qi Huang, Rui Zhou, Lu Li, Julie A. Maupin-Furlow
Journal of Bacteriology.2022;[Epub] CrossRef
Comparison of metabolic adaptation and biofilm formation of Actinobacillus pleuropneumoniae field isolates from the upper and lower respiratory tract of swine with respiratory disease
Doris Aper, Janna Frömbling, Murat Bağcıoğlu, Monika Ehling-Schulz, Isabel Hennig-Pauka
Veterinary Microbiology.2020; 240: 108532. CrossRef
Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria
Rajoana Rojony, Lia Danelishvili, Anaamika Campeau, Jacob M. Wozniak, David J. Gonzalez, Luiz E. Bermudez
Microorganisms.2020; 8(5): 698. CrossRef
Link between Heterotrophic Carbon Fixation and Virulence in the Porcine Lung Pathogen Actinobacillus pleuropneumoniae
Sarah A. Konze, Wolf-Rainer Abraham, Elke Goethe, Esther Surges, Marcel M. M. Kuypers, Doris Hoeltig, Jochen Meens, Charlotte Vogel, Meike Stiesch, Peter Valentin-Weigand, Gerald-F. Gerlach, Falk F. R. Buettner, Sabine Ehrt
Infection and Immunity.2019;[Epub] CrossRef
Actinobacillus pleuropneumoniae biofilms: Role in pathogenicity and potential impact for vaccination development
Skander Hathroubi, Abraham Loera-Muro, Alma L. Guerrero-Barrera, Yannick D. N. Tremblay, Mario Jacques
Animal Health Research Reviews.2018; 19(1): 17. CrossRef
Update onActinobacillus pleuropneumoniae-knowledge, gaps and challenges
E. L. Sassu, J. T. Bossé, T. J. Tobias, M. Gottschalk, P. R. Langford, I. Hennig-Pauka
Transboundary and Emerging Diseases.2018; 65: 72. CrossRef
Frequency of Th17 cells correlates with the presence of lung lesions in pigs chronically infected with Actinobacillus pleuropneumoniae
Elena L. Sassu, Andrea Ladinig, Stephanie C. Talker, Maria Stadler, Christian Knecht, Heiko Stein, Janna Frömbling, Barbara Richter, Joachim Spergser, Monika Ehling-Schulz, Robert Graage, Isabel Hennig-Pauka, Wilhelm Gerner
Veterinary Research.2017;[Epub] CrossRef
A Transcriptome Map of Actinobacillus pleuropneumoniae at Single-Nucleotide Resolution Using Deep RNA-Seq
Zhipeng Su, Jiawen Zhu, Zhuofei Xu, Ran Xiao, Rui Zhou, Lu Li, Huanchun Chen, Ying Xu
PLOS ONE.2016; 11(3): e0152363. CrossRef
Regulation of Escherichia coli RNase III activity
Boram Lim, Minji Sim, Howoon Lee, Seogang Hyun, Younghoon Lee, Yoonsoo Hahn, Eunkyoung Shin, Kangseok Lee
Journal of Microbiology.2015; 53(8): 487. CrossRef
Concurrent host-pathogen gene expression in the lungs of pigs challenged with Actinobacillus pleuropneumoniae
Louise Brogaard, Kirstine Klitgaard, Peter MH Heegaard, Mette Sif Hansen, Tim Kåre Jensen, Kerstin Skovgaard
BMC Genomics.2015;[Epub] CrossRef
Identification and characterization of a novel stress-responsive outer membrane protein Lip40 from Actinobacillus pleuropneumoniae
Xuehe Hu, Hao Yan, Ke Liu, Jiansheng Hu, Chao Qi, Jihong Yang, Yanli Liu, Jin Zhao, Jinlin Liu
BMC Biotechnology.2015;[Epub] CrossRef
Encyclopedia of bacterial gene circuits whose presence or absence correlate with pathogenicity – a large-scale system analysis of decoded bacterial genomes
Maksim Shestov, Santiago Ontañón, Aydin Tozeren
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Serotype-Independent Protection against Pneumococcal Infections Elicited by Intranasal Immunization with Ethanol-Killed Pneumococcal Strain, SPY1: Xiuyu Xu , Jiangping Meng , Yiping Wang , Jie Zheng , Kaifeng Wu , Xuemei Zhang , Yibing Yin , Qun Zhang; J. Microbiol. 2014;52(4):315-323. Published online March 29, 2014; DOI: https://doi.org/10.1007/s12275-014-3583-5

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Abstract

The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine are licensed vaccines that protect against pneumococcal infections worldwide. However, the incidence of pneumococcal diseases remains high in lowincome countries. Whole-cell vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70% ethanol and intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal pneumococcal infection were comparable to those of currently used polysaccharide vaccines. In addition, vaccinespecific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70% ethanolinactivated pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex vaccine strategy that offers broad protection against S. pneumoniae.

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Otitis media: recent advances in otitis media vaccine development and model systems
Ayesha Zahid, Jennifer C. Wilson, I. Darren Grice, Ian R. Peak
Frontiers in Microbiology.2024;[Epub] CrossRef
Corrected and Republished from: “A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge”
Win-Yan Chan, Claire Entwisle, Giuseppe Ercoli, Elise Ramos-Sevillano, Ann McIlgorm, Paola Cecchini, Christopher Bailey, Oliver Lam, Gail Whiting, Nicola Green, David Goldblatt, Jun X. Wheeler, Jeremy S. Brown, Liise-anne Pirofski
Infection and Immunity.2022;[Epub] CrossRef
Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection
Pedro H. Silva, Yaneisi Vázquez, Camilo Campusano, Angello Retamal-Díaz, Margarita K. Lay, Christian A. Muñoz, Pablo A. González, Alexis M. Kalergis, Susan M. Bueno
Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates
Julio Sempere, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech, Fernando González-Camacho
Vaccines.2021; 9(2): 181. CrossRef
Immune Responses to Irradiated Pneumococcal Whole Cell Vaccine
Eunbyeol Ko, Soyoung Jeong, Min Yong Jwa, A Reum Kim, Ye-Eun Ha, Sun Kyung Kim, Sungho Jeong, Ki Bum Ahn, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
Vaccines.2021; 9(4): 405. CrossRef
Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens
Theano Lagousi, Paraskevi Basdeki, John Routsias, Vana Spoulou
Vaccines.2019; 7(1): 9. CrossRef
A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge
Win-Yan Chan, Claire Entwisle, Giuseppe Ercoli, Elise Ramos-Sevillano, Ann McIlgorm, Paola Cecchini, Christopher Bailey, Oliver Lam, Gail Whiting, Nicola Green, David Goldblatt, Jun X. Wheeler, Jeremy S. Brown, Liise-anne Pirofski
Infection and Immunity.2019;[Epub] CrossRef
Efficacy of whole-cell pneumococcal vaccine in mice: A systematic review and meta-analysis
Mona Mohammadzadeh, Babak Pourakbari, Shima Mahmoudi, Abbas Keshtkar, Mahdi Habibi-Anbouhi, Setareh Mamishi
Microbial Pathogenesis.2018; 122: 122. CrossRef
Construction and evaluation of a whole-cell pneumococcal vaccine candidate
M. Mohammadzadeh, B. Pourakbari, A. Doosti, S. Mahmoudi, M. Habibi-Anbouhi, S. Mamishi
Journal of Applied Microbiology.2018; 125(6): 1901. CrossRef
Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine
Min Yong Jwa, Soyoung Jeong, Eun Byeol Ko, A Reum Kim, Hyun Young Kim, Sun Kyung Kim, Ho Seong Seo, Cheol-Heui Yun, Seung Hyun Han
Journal of Microbiology.2018; 56(8): 579. CrossRef
spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection
Lingling Gan, Xuemei Zhang, Xiuyu Xu, Wenchun Xu, Chang Lu, Jin Cui, Hong Wang
Canadian Journal of Microbiology.2018; 64(6): 401. CrossRef
Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice
Yulan Qiu, Xuemei Zhang, Hong Wang, Xinyuan Zhang, Yunjun Mo, Xiaoyu Sun, Jichao Wang, Yibing Yin, Wenchun Xu
Journal of Microbiology.2017; 55(10): 823. CrossRef
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Melinda M. Pettigrew, Mark R. Alderson, Lauren O. Bakaletz, Stephen J. Barenkamp, Anders P. Hakansson, Kevin M. Mason, Johanna Nokso‐Koivisto, Janak Patel, Stephen I. Pelton, Timothy F. Murphy
Otolaryngology–Head and Neck Surgery.2017;[Epub] CrossRef
Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic cell activation and drives a Th1/Th17 response
Song Gao, Lingbin Zeng, Xuemei Zhang, Yingying Wu, Jingjing Cui, Zhixin Song, Xiaoyu Sun, Hong Wang, Yibing Yin, Wenchun Xu
Immunology Letters.2016; 179: 47. CrossRef
SEROTYPE-INDEPENDENT VACCINES AGAINST PNEUMOCOCCAL INFECTION
I. B. Semenova, N. A. Mikhailova
Journal of microbiology, epidemiology and immunobiology.2016; 93(4): 76. CrossRef
Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young mice
Lingbin Zeng, Yusi Liu, Hong Wang, Pu Liao, Zhixin Song, Song Gao, Yingying Wu, Xuemei Zhang, Yibing Yin, Wenchun Xu
Vaccine.2015; 33(8): 1008. CrossRef
Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection
Xiuyu Xu, Hong Wang, Yusi Liu, Yiping Wang, Lingbing Zeng, Kaifeng Wu, Jianmin Wang, Feng Ma, Wenchun Xu, Yibing Yin, Xuemei Zhang, A. Camilli
Infection and Immunity.2015; 83(1): 90. CrossRef

Characterization of Streptococcus pneumoniae N-Acetylglucosamine-6-Phosphate Deacetylase as a Novel Diagnostic Marker: Chi-Won Choi , Hee-Young An , Yong Ju Lee , Yeol Gyun Lee , Sung Ho Yun , Edmond Changkyun Park , Yeonhee Hong , Gun-Hwa Kim , Jae-Eun Park , Sun Jong Baek , Hyun Sik Kim , Seung Il Kim; J. Microbiol. 2013;51(5):659-664. Published online October 31, 2013; DOI: https://doi.org/10.1007/s12275-013-3451-8

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Abstract

The identification of novel diagnostic markers of pathogenic bacteria is essential for improving the accuracy of diagnoses and for developing targeted vaccines. Streptococcus pneumoniae is a significant human pathogenic bacterium that causes pneumonia. N-acetylglucosamine-6-phosphate deacetylase (NagA) was identified in a protein mixture secreted by S. pneumoniae and its strong immunogenicity was confirmed in an immuno-proteomic assay against the anti-serum of the secreted protein mixture. In this study, recombinant S. pneumoniae NagA protein was expressed and purified to analyze its protein characteristics, immunospecificity, and immunogenicity, thereby facilitating its evaluation as a novel diagnostic marker for S. pneumoniae. Mass spectrometry analysis showed that S. pneumoniae NagA contains four internal disulfide bonds and that it does not undergo posttranslational modification. S. pneumoniae NagA antibodies successfully detected NagA from different S. pneumoniae strains, whereas NagA from other pathogenic bacteria species was not detected. In addition, mice infected with S. pneumoniae generated NagA antibodies in an effective manner. These results suggest that NagA has potential as a novel diagnostic marker for S. pneumoniae because of its high immunogenicity and immunospecificity.

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Multi-omic profiling to assess the effect of iron starvation inStreptococcus pneumoniaeTIGR4
Irene Jiménez-Munguía, Mónica Calderón-Santiago, Antonio Rodríguez-Franco, Feliciano Priego-Capote, Manuel J. Rodríguez-Ortega
PeerJ.2018; 6: e4966. CrossRef
Mycoplasma fermentans deacetylase promotes mammalian cell stress tolerance
Qingzhou Cheng, Lijuan Wu, Rongfu Tu, Jun Wu, Wenqian Kang, Tong Su, Runlei Du, Wenbin Liu
Microbiological Research.2017; 201: 1. CrossRef
Serotype IV Sequence Type 468 Group BStreptococcusNeonatal Invasive Disease, Minnesota, USA
Sarah Teatero, Patricia Ferrieri, Nahuel Fittipaldi
Emerging Infectious Diseases.2016; 22(11): 1937. CrossRef
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Frank Fleurbaaij, Hans C. van Leeuwen, Oleg I. Klychnikov, Ed J. Kuijper, Paul J. Hensbergen
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Screening and Identification of ClpE Interaction Proteins in Streptococcus pneumoniae by a Bacterial Two-Hybrid System and Co-immunoprecipitation: WenJuan Yan , YingYing Cai , Qun Zhang , YuSi Liu , WenChun Xu , YiBing Yin , YuJuan He , Hong Wang , XueMei Zhang; J. Microbiol. 2013;51(4):453-460. Published online August 30, 2013; DOI: https://doi.org/10.1007/s12275-013-3001-4

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Abstract: Hsp100/Clp proteins have crucial functions in the protein quality control, stress tolerance, and virulence of many pathogenic bacteria. ClpE is an important virulence factor involved in adherence and invasion in Streptococcus pneumoniae. To explore the underlying mechanism, we screened ClpE interaction proteins using a bacterial two-hybrid system and co-immunoprecipitation. We used ClpE as bait and constructed the pBT-ClpE bait plasmid for two-hybrid screening. Then, we constructed ClpE::GFP fusion for co-immunoprecipitation screening using anti-GFP monoclonal antibody. We obtained eight potential ClpE interaction proteins, including carbamoyl-phosphate synthase, pyruvate oxidase (SpxB), phosphoenolpyruvate-protein phosphotransferase, aminopeptidase N (pepN), L-lactate dehydrogenase, ribosomal protein S4, sensor histidine kinase (SPD_2019), and FtsW (a cell division protein). FtsW, SpxB, pepN, and SPD_2019 were confirmed to interact with ClpE using Bacterial Two-hybrid or Co-immunoprecipitation. Morphologic observations found that ΔclpE strain existed in abnormal division. β-Galactosidase activity assay suggested that ClpE contributed to the degradation of FtsW. Furthermore, FtsW could be induced by heat shock. The results suggested that ClpE might affect cell division by regulating the level of FtsW. These data may provide new insights in studying the role of ClpE in S. pneumoniae.

Identification of Conserved Surface Proteins as Novel Antigenic Vaccine Candidates of Actinobacillus pleuropneumoniae: Xiabing Chen , Zhuofei Xu , Lu Li , Huanchun Chen , Rui Zhou; J. Microbiol. 2012;50(6):978-986. Published online December 30, 2012; DOI: https://doi.org/10.1007/s12275-012-2214-2

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Abstract: Actinobacillus pleuropneumoniae is an important swine respiratory pathogen causing great economic losses worldwide. Identification of conserved surface antigenic proteins is helpful for developing effective vaccines. In this study, a genome-wide strategy combined with bioinformatic and experimental approaches, was applied to discover and characterize surface-associated immunogenic proteins of A. pleuropneumoniae. Thirty nine genes encoding outer membrane proteins (OMPs) and lipoproteins were identified by comparative genomics and gene expression profiling as beinghighly conserved and stably transcribed in the different serotypes of A. pleuropneumoniae reference strains. Twelve of these conserved proteins were successfully expressed in Escherichia coli and their immunogenicity was estimated by homologous challenge in the mouse model, and then three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae. This study gives novel insights into immunogenicity of the conserved OMPs and lipoproteins of A. pleuropneumoniae. Although none of the surface proteins characterized in this study could individually induce effective protective immunity against A. pleuropneumoniae, they are potential candidates for subunit vaccines in combination with Apx toxins.

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