Journal of Microbiology

Journal Articles

Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status: Yingying Ma , Yanpeng Li , Yanmei Liu , Le Cao , Xiao Han , Shujun Gao , Chiyu Zhang; J. Microbiol. 2023;61(4):423-432. Published online April 3, 2023; DOI: https://doi.org/10.1007/s12275-023-00039-3

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Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.

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Vaginal Microbiome and Pregnancy Complications: A Review
Angeliki Gerede, Konstantinos Nikolettos, Eleftherios Vavoulidis, Chrysoula Margioula-Siarkou, Stamatios Petousis, Maria Giourga, Panagiotis Fotinopoulos, Maria Salagianni, Sofoklis Stavros, Konstantinos Dinas, Nikolaos Nikolettos, Ekaterini Domali
Journal of Clinical Medicine.2024; 13(13): 3875. CrossRef
Advancements in the Vaginal Microenvironment and Regression of High-Risk Human Papillomavirus
Na He, Cunjian Yi, Qingsong Zeng, Wumei Jing, Wenrong He
Indian Journal of Microbiology.2024;[Epub] CrossRef
Research Progress on Related Factors of Cervical High-Grade Squamous Intraepithelial Lesions
红颖王
Advances in Clinical Medicine.2023; 13(12): 20536. CrossRef
Role of the vaginal microbiome in miscarriage: exploring the relationship
Marwa Saadaoui, Parul Singh, Osman Ortashi, Souhaila Al Khodor
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

Gamma-glutamyltransferase of Helicobacter pylori alters the proliferation, migration, and pluripotency of mesenchymal stem cells by affecting metabolism and methylation status: Zeyu Wang , Weijun Wang , Huiying Shi , Lingjun Meng , Xin Jiang , Suya Pang , Mengke Fan , Rong Lin; J. Microbiol. 2022;60(6):627-639. Published online April 18, 2022; DOI: https://doi.org/10.1007/s12275-022-1575-4

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Abstract

Virulence factor gamma-glutamyltransferase (GGT) of H. pylori consumes glutamine (Gln) in the stomach to decrease the tricarboxylic acid metabolite alpha-ketoglutarate (α-kg) and alter the downstream regulation of α-kg as well as cellular biological characteristics. Our previous research indicated that under H. pylori infection, mesenchymal stem cells (MSCs) migrated to the stomach and participated in gastric cancer (GC) development either by differentiating into epithelial cells or promoting angiogenesis. However, how MSCs themselves participate in H. pylori-indicated GC remains unclear. Therefore, a GGT knockout H. pylori strain (Hp- KS-1) was constructed, and downstream histone H3K9 and H3K27 methylation and the PI3K/AKT signaling pathway of α-kg were detected using Western blotting. The biological characteristics of MSCs were also examined. An additive α-kg supplement was also added to H. pylori-treated MSCs to investigate alterations in these aspects. Compared to the control and Hp-KS-1 groups, H. pylori-treated MSCs reduced Gln and α-kg, increased H3K9me3 and H3K27me3, activated the PI3K-AKT signaling pathway, and promoted the proliferation, migration, self-renewal, and pluripotency of MSCs. The addition of α-kg rescued the H. pylori-induced alterations. Injection of MSCs to nude mice resulted in the largest tumors in the H. pylori group and significantly reduced tumor sizes in the Hp-KS-1 and α-kg groups. In summary, GGT of H. pylori affected MSCs by interfering with the metabolite α-kg to increase trimethylation of histone H3K9 and H3K27, activating the PI3K/AKT signaling pathway, and promoting proliferation, migration, self-renewal, and pluripotency in tumorigenesis, elucidating the mechanisms of MSCs in GC development.

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Gamma-glutamyl transferase secreted by Helicobacter pylori promotes the development of gastric cancer by affecting the energy metabolism and histone methylation status of gastric epithelial cells
Xin Jiang, Weijun Wang, Zeyu Wang, Zhe Wang, Huiying Shi, Lingjun Meng, Suya Pang, Mengke Fan, Rong Lin
Cell Communication and Signaling.2024;[Epub] CrossRef
Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics
Man Cui, Xiaohui Ji, Fengtao Guan, Guimin Su, Lin Du
Frontiers in Immunology.2024;[Epub] CrossRef
Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles
Maryam Dolatshahi, Ahmad Reza Bahrami, Qaiser Iftikhar Sheikh, Mohsen Ghanbari, Maryam M. Matin
Archives of Pharmacal Research.2024; 47(1): 1. CrossRef
Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer
Fawzy Akad, Veronica Mocanu, Sorin Nicolae Peiu, Viorel Scripcariu, Bogdan Filip, Daniel Timofte, Florin Zugun-Eloae, Magdalena Cuciureanu, Monica Hancianu, Teodor Oboroceanu, Laura Condur, Radu Florin Popa
Biomedicines.2023; 11(4): 1031. CrossRef
Helicobacter pylori and Its Role in Gastric Cancer
Victor E. Reyes
Microorganisms.2023; 11(5): 1312. CrossRef

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

Complementation System for Helicobacter pylori: Jinmoon Kim , Sung-Whan Kim , Sungil Jang , D. Scott Merrell , Jeong-Heon Cha; J. Microbiol. 2011;49(3):481-486. Published online June 30, 2011; DOI: https://doi.org/10.1007/s12275-011-1196-9

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Abstract: Previously Langford et al. (2006) developed the pIR203C04 complementation system for Helicobacter pylori, which can be used to complement and restore phenotypic effects in H. pylori mutant, and furthermore they used the complementation system in vivo experiments to animals without altering the ability of strain SS1 to colonize mice. In their previous study, the pIR203C04 was able to transform 26695, SS1, J99, and 43504 H. pylori strains by an electroporation method. However, in the present study using a natural transformation the pIR203C04 transformed only 26695 H. pylori but not SS1, J99, 7.13, and G27 H. pylori strains. Since the useful complementation system has a limitation of narrow selection among H. pylori strains, we redesigned the complementation system for the improvement. The same intergenic chromosomal site between hp0203 and hp0204 was utilized for the new complementation system because the insertion at the intergenic site didn’t show any polar effects and disruption of other H. pylori genes. The genome sequence analysis showed that the intergenic regions among H. pylori strains may have too low homology to each others to do a homologous recombination. Thus, in addition to the short intergenic region, the fragments of the new complementation system included 3′ conserved parts of hp0203 and hp0204 coding regions. Between the fragments there are a chloramphenicol acetyltransferase cassette and multicloning sites, resulting in pKJMSH. DNA fragment of the interest can be cloned into the multicloning sites of pKJMSH and the fragment can be integrated at the intergenic region of H. pylori chromosome by the homologous recombination. Indeed, by the natural transformation, pKJMSH was able to transform all five H. pylori strains of 26695, SS1, J99, 7.13, and G27, which are common for the investigation of molecular pathogenesis. Thus, the new pKJMSH complementation system is applicable to most H. pylori wild-type stains.

Helicobacter pylori γ-Glutamyltranspeptidase Induces Cell Cycle Arrest at the G1-S Phase Transition: Kyung-Mi Kim , Seung-Gyu Lee , Jung-Min Kim , Do-Su Kim , Jea-Young Song , Hyung-Lyun Kang , Woo-Kon Lee , Myung-Je Cho , Kwang-Ho Rhee , Hee-Shang Youn , Seung-Chul Baik; J. Microbiol. 2010;48(3):372-377. Published online June 23, 2010; DOI: https://doi.org/10.1007/s12275-010-9293-8

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Abstract: In our previous study, we showed that Helicobacter pylori γ-glutamyltranspeptidase (GGT) is associated with H. pylori-induced apoptosis through a mitochondrial pathway. To better understand the role of GGT in apoptosis, we examined the effect of GGT on cell cycle regulation in AGS cells. To determine the effect of recombinant GGT (rGGT) on cell cycle distribution and apoptosis, rGGT-treated and untreated AGS cells were analyzed in parallel by flow cytometry using propidium iodide (PI). We found that rGGT inhibited the growth of AGS cells in a time-dependent manner, and that the pre-exposure of cells to a caspase-3 inhibitor (z-DEVD-fmk) effectively blocked GGT-induced apoptosis. Cell cycle analysis showed G1 phase arrest and apoptosis in AGS cells following rGGT treatment. The rGGT-mediated G1 phase arrest was found to be associated with down-regulation of cyclin E, cyclin A, Cdk 4, and Cdk 6, and the up-regulation of the cyclindependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition.

Research Support, N.I.H., Extramural

Helicobacter pylori apo-Fur Regulation Appears Unconserved Across Species: Shana Miles , Beth M. Carpenter , Hanan Gancz , D. Scott Merrell; J. Microbiol. 2010;48(3):378-386. Published online June 23, 2010; DOI: https://doi.org/10.1007/s12275-010-0022-0

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Abstract: The Ferric Uptake Regulator (Fur) is a transcriptional regulator that is conserved across a broad number of bacterial species and has been shown to regulate expression of iron uptake and storage genes. Additionally, Fur has been shown to be an important colonization factor of the gastric pathogen Helicobacter pylori. In H. pylori, Fur-dependent regulation appears to be unique in that Fur is able to act as a transcriptional repressor when bound to iron as well as in its iron free (apo) form. To date, apo-regulation has not been identified in any other bacterium. To determine whether Fur from other species has the capacity for aporegulation, we investigated the ability of Fur from Escherichia coli, Campylobacter jejuni, Desulfovibrio vulgaris Hildenborough, Pseudomonas aeruginosa, and Vibrio cholerae to complement both iron-bound and apo-Fur regulation within the context of a H. pylori fur mutant. We found that while some Fur species (E. coli, C. jejuni, and V. cholerae) complemented iron-bound regulation, apo-regulation was unable to be complemented by any of the examined species. These data suggest that despite the conservation among bacterial Fur proteins, H. pylori Fur contains unique structure/function features that make it novel in comparison to Fur from other species.

Research Support, Non-U.S. Gov't

Protection Against Helicobacter pylori Infection by a Trivalent Fusion Vaccine Based on a Fragment of Urease B-UreB414: Li Wang Wang , Xiao-Fei Liu , Shi Yun , Xiao-Peng Yuan , Xu-Hu Mao , Chao Wu , Wei-Jun Zhang , Kai-Yun Liu , Gang Guo , Dong-Shui Lu , Wen-De Tong , Ai-Dong Wen , Quan-Ming Zou; J. Microbiol. 2010;48(2):223-228. Published online May 1, 2010; DOI: https://doi.org/10.1007/s12275-009-0233-4

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Abstract: A multivalent fusion vaccine is a promising option for protection against Helicobacter pylori infection. In this study, UreB414 was identified as an antigenic fragment of urease B subunit (UreB) and it induced an antibody inhibiting urease activity. Immunization with UreB414 partially protected mice from H. pylori infection. Furthermore, a trivalent fusion vaccine was constructed by genetically linking heat shock protein A (HspA), H. pylori adhesin A (HpaA), and UreB414, resulting in recombinant HspA-HpaA-UreB414 (rHHU). Its protective effect against H. pylori infection was tested in BALB/c mice. Oral administration of rHHU significantly protected mice from H. pylori infection, which was associated with H. pylori-specific antibody production and Th1/Th2-type immune responses. The results show that a trivalent fusion vaccine efficiently combats H. pylori infection, and that an antigenic fragment of the protein can be used instead of the whole protein to construct a multivalent vaccine.

Journal Article

Claritromycin Resistance and Helicobacter pylori Genotypes in Italy: Vincenzo De Francesco , Marcella Margiotta , Cesare Hassan , Nicola Della Valle , Osvaldo Burattini , Roberto D’Angelo , Giuseppe Stoppino , Ugo Cea , Floriana Giorgio , Rosa Monno , Sergio Morini , Carmine Panella , Enzo Ierardi; J. Microbiol. 2006;44(6):660-664.; DOI: https://doi.org/2460 [pii]

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Abstract: The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1% of cases. The prevalence of cagA was 69.3%, and a single vacA mosaicism was observed in 95.1% cases. In detail, the s1m1 was observed in 23 (38.9%) patients, the s1m2 in 22 (37.2%), and the s2m2 in 14 (23.7%), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

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