Journal of Microbiology

Journal Article

The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles: Uzma Qaisar , Cassandra J. Kruczek , Muhammed Azeem , Nasir Javaid , Jane A. Colmer-Hamood , Abdul N. Hamood; J. Microbiol. 2016;54(8):573-581. Published online August 2, 2016; DOI: https://doi.org/10.1007/s12275-016-5645-3

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Proteins encoded by the Pseudomonas aeruginosa pvcA-D operon synthesize a novel isonitrile functionalized cumarin termed paerucumarin. The pvcA-D operon enhances the expression of the P. aeruginosa fimbrial chaperone/usher pathway (cup) genes and this effect is mediated through paerucumarin. Whether pvcA-D and/or paerucumarin affect the expression of other P. aeruginosa genes is not known. In this study, we examined the effect of a mutation in pvcA-D operon the global transcriptome of the P. aeruginosa strain PAO1- UW. The mutation reduced the expression of several ironcontrolled genes including pvdS, which is essential for the expression of the pyoverdine genes. Additional transcriptional studies showed that the pvcA-D operon is not regulated by iron. Exogenously added paerucumarin enhanced pyoverdine production and pvdS expression in PAO1-UW. Iron-chelation experiments revealed that purified paerucumarin chelates iron. However, exogenously added paerucumarin significantly reduced the growth of a P. aeruginosa mutant defective in pyoverdine and pyochelin production. In contrast to other secondary metabolite, Pseudomonas quinolone signal (PQS), paerucumarin is not localized to the P. aeruginosa membrane vesicles. These results suggest that paerucumarin enhances the expression of iron-controlled genes by chelating iron within the P. aeruginosa extracellular environment. Although paerucumarin chelates iron, it does not function as a siderophore. Unlike PQS, paerucumarin is not associated with the P. aeruginosa cell envelope.

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Bacterial extracellular vesicles: Vital contributors to physiology from bacteria to host
Xinke Nie, Qiqiong Li, Xinyang Chen, Stanley Onyango, Junhua Xie, Shaoping Nie
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Natural and synthetic molecules with potential to enhance biofilm formation and virulence properties in Pseudomonas aeruginosa
Geum-Jae Jeong, Fazlurrahman Khan, Nazia Tabassum, Young-Mog Kim
Critical Reviews in Microbiology.2024; 50(5): 830. CrossRef
Advances in mechanism for the microbial transformation of heavy metals: implications for bioremediation strategies
Chunlian Ding, Zihan Ding, Qingcai Liu, Weizao Liu, Liyuan Chai
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Rosaleen Sahoo, Narendra Kadoo
Journal of Molecular Liquids.2024; 399: 124364. CrossRef
Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa
Ana Sánchez-Jiménez, María A. Llamas, Francisco Javier Marcos-Torres
International Journal of Molecular Sciences.2023; 24(15): 11895. CrossRef
Biosynthesis of Isonitrile- and Alkyne-Containing Natural Products
Antonio Del Rio Flores, Colin C. Barber, Maanasa Narayanamoorthy, Di Gu, Yuanbo Shen, Wenjun Zhang
Annual Review of Chemical and Biomolecular Engineering.2022; 13(1): 1. CrossRef
Medicinal Chemistry of Isocyanides
Alberto Massarotti, Francesca Brunelli, Silvio Aprile, Mariateresa Giustiniano, Gian Cesare Tron
Chemical Reviews.2021; 121(17): 10742. CrossRef
Current Understanding toward Isonitrile Group Biosynthesis and Mechanism
Tzu‐Yu Chen, Jinfeng Chen, Yijie Tang, Jiahai Zhou, Yisong Guo, Wei‐chen Chang
Chinese Journal of Chemistry.2021; 39(2): 463. CrossRef
Mutation in pvcABCD operon of Pseudomonas aeruginosa modulates MexEF-OprN efflux system and hence resistance to chloramphenicol and ciprofloxacin
Anam Iftikhar, Azka Asif, Asma Manzoor, Muhammad Azeem, Ghulam Sarwar, Naeem Rashid, Uzma Qaisar
Microbial Pathogenesis.2020; 149: 104491. CrossRef
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Novel intermicrobial molecular interaction: Pseudomonas aeruginosa Quinolone Signal (PQS) modulates Aspergillus fumigatus response to iron
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An Aqueous Extract of Yunnan Baiyao Inhibits the Quorum-Sensing-Related Virulence of Pseudomonas aeruginosa: Zu-Guo Zhao , Shuang-Shuang Yan , Yun-Mei Yu , Na Mi , La-Xi Zhang , Jun Liu , Xiao-Ling Li , Fang Liu , Jun-Fa Xu , Wei-Qing Yang , Guo-Ming Li; J. Microbiol. 2013;51(2):207-212. Published online April 27, 2013; DOI: https://doi.org/10.1007/s12275-013-2595-x

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Abstract: Yunnan Baiyao is a famous Chinese medicine that has long been directly applied to wounds to reduce bleeding, pain, and swelling without causing infection. However, little is known about its ability to prevent infection. The present study aimed to assess in vitro the anti-virulence activity of an aqueous extract of Yunnan Baiyao (YBX) using Pseudomonas aeruginosa as a pathogenic model. We found that a sub-MIC (2.5 mg/ml) of YBX can efficiently interfere with the quorum-sensing (QS) signaling circuit. Real-time polymerase chain reaction analysis showed that a sub-MIC of YBX downregulated the transcriptions of lasR, lasI, rhlR, and rhlI, which resulted in global attenuation of QS-regulated virulence activities, such as biofilm formation, and secretion of LasA protease, LasB elastase and pyocyanin. Further, YBX reduced the motility of P. aeruginosa related to QS, and impaired the formation of biofilms. These results suggest that YBX may possess global inhibitory activity against the virulence of P. aeruginosa and that YBX may also exhibit antimicrobial activity in vivo. The present study suggests that Yunnan Baiyao represents a potential source for isolating novel, safe, and efficacious antimicrobial agents.

Inactivation of MuxABC-OpmB Transporter System in Pseudomonas aeruginosa Leads to Increased Ampicillin and Carbenicillin Resistance and Decreased Virulence: Liang Yang , Lin Chen , Lixin Shen , Michael Surette , Kangmin Duan; J. Microbiol. 2011;49(1):107-114. Published online March 3, 2011; DOI: https://doi.org/10.1007/s12275-011-0186-2

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Abstract: Resistance-Nodulation-Cell Division (RND) pumps play important roles in bacterial resistance to antibiotics. Pseudomonas aeruginosa is an important human pathogen which exhibits high level resistance to antibiotics. There are total of 12 RND pumps present in the P. aeruginosa PAO1 genome. The recently characterized MuxABC-OpmB system has been shown to play a role in resistance to novobiocin, aztreonam, macrolides, and tetracycline in a multiple knockout mutation. In this study, we examined the expression levels of all the 12 RND pump gene clusters and tested the involvement of MuxABC-OpmB in pathogenicity. The results indicated that in addition to the four known constitutively expressed RND pumps, mexAB-oprM, mexGHIopmD, mexVW, and mexXY, relatively high levels of expression were observed with mexJK and muxABCopmB in the conditions tested. Inactivation of muxA in the muxABC-opmB operon resulted in elevated resistance to ampicillin and carbenicillin. The mutant also showed attenuated virulence in both Brassica rapa pekinensis and Drosophila melanogaster infection models. The decreased virulence at least in part was due to decreased twitching motility in the mutant. These results indicate that the RND pump MuxABC-OpmB is associated with ampicillin and carbenicillin susceptibility and also involved in pathogenesis in P. aeruginosa.

Heterogeneous Virulence Potential and High Antibiotic Resistance of Pseudomonas aeruginosa Strains Isolated from Korean Pneumonia Patients: Mi Young Yoon , Kang-Mu Lee , Seok Hoon Jeong , Jungmin Kim , Sang Sun Yoon; J. Microbiol. 2010;48(4):518-525. Published online August 20, 2010; DOI: https://doi.org/10.1007/s12275-010-9388-2

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Abstract

Pseudomonas aeruginosa is an opportunistic human pathogen of clinical importance that causes airway infections in immunocompromised patients. Here, we report the virulence-associated characteristics of strains of P. aeruginosa, isolated from the sputa of 25 Korean pneumonia patients. A high degree of genomic plasticity was observed by random amplified polymorphic DNA genotype analysis, suggesting that the infections were caused by strains with diverse genomic backgrounds. Biofilm formation of each isolate was heterogeneous in terms of their relative motilities. In addition, 48% of isolates were defective in the production of 3-oxo-C12-HSL (PAI-1), a quorum sensing signal molecule. In these strains, PAI-1-dependent elastase production was correspondingly decreased, suggesting that a large number of strains were presumed to be quorum sensing deficient. Multidrug resistance (MDR) was seen in 56% of the isolates tested, and 44% of the MDR strains were resistant to five or more antibiotics. Taken together, our results provide additional insights into the virulence traits of P. aeruginosa clinical isolates, which will aid in treating P. aeruginosa infections in pneumonia patients.

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Virulence Characteristics and an Action Mode of Antibiotic Resistance in Multidrug-Resistant Pseudomonas aeruginosa
Wontae Hwang, Sang Sun Yoon
Scientific Reports.2019;[Epub] CrossRef
The ferrichrome receptor A as a new target forPseudomonas aeruginosavirulence attenuation
Keehoon Lee, Kang-Mu Lee, Junhyeok Go, Jae-Chan Ryu, Ji-Hwan Ryu, Sang Sun Yoon, Klaus Hantke
FEMS Microbiology Letters.2016; 363(11): fnw104. CrossRef
A single gene of a commensal microbe affects host susceptibility to enteric infection
Mi Young Yoon, Kyung Bae Min, Kang-Mu Lee, Yujin Yoon, Yaeseul Kim, Young Taek Oh, Keehoon Lee, Jongsik Chun, Byung-Yong Kim, Seok-Hwan Yoon, Insuk Lee, Chan Yeong Kim, Sang Sun Yoon
Nature Communications.2016;[Epub] CrossRef
Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa
Kang-Mu Lee, Mi Young Yoon, Yongjin Park, Joon-Hee Lee, Sang Sun Yoon, B. A. McCormick
Infection and Immunity.2011; 79(7): 2792. CrossRef

Analysis of a Novel Class 1 Integron Containing Metallo-β-Lactamase Gene VIM-2 in Pseudomonas aeruginosa: Jae Hoon Jeong , Kyeong Seob Shin , Jang Won Lee , Eun Jin Park , Seung-Yeol Son; J. Microbiol. 2009;47(6):753-759. Published online February 4, 2010; DOI: https://doi.org/10.1007/s12275-008-0272-2

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Abstract: Carbapenems such as imipenem are stable to most β-lactamases. Recently, increased numbers of carbapenemase producing Gram-negative bacterial strains have been isolated because of the increased use of cabapenems. In this respect, control of these infectious carbapenemase producing Gram-negative bacteria and understanding their resistance mechanism are becoming more important. These carbapenem-hydrolyzing β-lactamase genes have been reported to exist mostly as gene cassettes in an integron. This implies that antibiotic resistance genes may be transferred to other bacteria via the integron. In the present study, we identified and analyzed an integron containing VIM-2 type metallo-β-lactamase gene in a carbapenemase producing Pseudomonas aeruginosa. In addition, the possibility of resistance spread by integron located in a plasmid was tested. Among glucose non-fermenting Gram-negative bacilli with reduced imipenem susceptibility (MIC≥8 μg/ml) isolated from Korean patients, P. aeruginosa 1082 showed resistance to most β-lactams, cephalosporin, and aminoglycoside. We found that P. aeruginosa 1082 was inhibited by EDTA in EDTA double disk synergy test which means that this strain produces metallo-β-lactamase. Class 1 integron containing blaVIM-2 (carbapenem resistance gene), qacF (quaternary ammonium compound resistance gene), aacA4 (aminoglycoside resistance gene), catB3 (chloramphenicol resistance gene), blaOXA-30 (extended-spectrum β-lactam resistance gene), and aadA1 (aminoglycoside resistance gene) gene cassettes was detected in P. aeruginosa 1082. The size of the integron was 5,246 bp and the structure and arrangement of the integron was a novel one in comparison with other integrons found in other P. aeruginosa. The integron could be transferred to Escherichia coli JM109 from P. aeruginosa 1082 possibly via self-transferable plasmid DNA. The integron and a blaVIM-2 gene were detected in the plasmid DNA of the transconjugants whose imipenem resistance was slightly increased as a result of accepting the integron from the donor strain.

A Novel Immunodominant Epitope on aouter Membrane protein F of Pseudomonas aeruginosa in Humans: Park, Wan Je , Lee, Na Gyong , Jung, Sang Bo , Ahn, Bo Young , Kim, Yu Sam , Kim, Hyun Su; J. Microbiol. 1998;36(1):49-54.

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Abstract: The outer membrane protein F(OprF) of Pseudomonas aeruginosa is known to be conserved among various P. aeruginosa strains, and has been shown to be protective against P. aeruginosa infections in animal model systems. In order to identify epitopes essential for immunogenicity and protective efficacy, we synthesized 14 peptides of the mature OprF protein and evaluated their immunofenicity in mice. Among them two peptides in the carboxy-terminus region of OprF, peptide 3(^204GAPAVAEVVRVQLDVKFD^221) and peptide 14(^305NATAEGRAINRRVE^318), elicited high titer of antibody responses in mices, and reacted strongly with anti-OprF antibodies. The peptides were also examined for reactivity with antisera from human volunteers immunized with a P. aeruginosa vaccine composed of outer membrane proteins and from patients who recovered from Pseudomons infections. Peptide 3 showed high reactivity with both antisera from the vaccines and the convalescents, comparable to that of peptide 14, which has been previously reported to afford protection against P. aeruginosa in a murine acute infection model. Substitution of three amino acids KFD in peptide 3 with AAA significantly diminished its reactivity to the antisera, indicating that the core sequence ^216LDVKFD^221 is crucial for its immunogenicity and reactivity with human antisera. These data suggest a potential use of this peptide for development of a vaccine against P. aeruginosa infection.

Acyl-Homoserine Lactone Quorum Sensing in Bacteria: E. Peter Greenberg; J. Microbiol. 2000;38(3):117-121.

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Abstract: Recent advances in studies of bacterial gene expression and light microscopy show that cell-to-cell communication and community behavior are the rule rather than the exception. One type of cell-cell communication, quorum sensing in Gram-negative bacteria involves acyl-homoserine lactone signals. This type of quorum sensing represents a dedicated communication system that enables a given species to sense when it has reached a critical population density, and to respond by activating expression of specific genes. The LuxR and LuxI proteins of Vibrio fisheri are the founding members of the acyl-homoserine lactone quorum sensing signal receptor and signal generator families of proteins. Acyl-homoserine lactone signaling in Pseudomonas aeruginosa is one model for the relationship between quorum sensing, community behavior, and virulence. In the P. aeruginosa model, quorum sensing is required for normal biofilm maturation and virulence. There are multiple quorum-sensing circuits that control the expression of dozens of specific genes in P. aeruginosa.

Iron Increases Susceptibilities of Pseudomonas aeruginosa to Ofloxacin by Increasing the Permeability: Sookyoung Kim , Jinsook Kim , Hyeran Nam , Yusun Jung , Yeonhee Lee; J. Microbiol. 2000;38(4):265-269.

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Abstract: Iron increased the susceptibilities of clinical isolates of Pseudomonas aeruginosa to quinolones. In the presence of iron, increased susceptibilities to ofloxacin were observed in twenty-six out of thirty isolates and with no change in four isolates. In the case of norfloxacin, iron increased susceptibilities of twelve isolates but did not render any change in eighteen isolates. In the case of ciprofloxacin, iron decreased the MICs (Minimal Inhibitory Concentration) of twenty isolates, increased the MIC of one isolate, and did not change the MICs of nine isolates. To find out how iron increased susceptibility to ofloxacin, bacterial cells were grown in Muller Hinton (MH) media and succinate minimal media (SMM) to induce iron acquisition systems and the intracellular ofloxacin concentrations were assayed in the presence of iron. The addition of iron to the media decreased the MICs of cells whether they were grown in MH or SMM. Siderophores, carbonyl cyanide m-chlorophenylhydrazone (an inhibitor of proton motive force), and ouabain (an inhibitor of ATPase) did not decrease the effect of iron. Results suggested that the increase in the intracellular ofloxacin concentration by iron is accomplished not by decreasing the efflux but by increasing the ofloxacin permeability.

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