Metabolomics
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2017
·Vol. 13
·期 12
·1-14
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IF 3.692
Tang Tian,Gao Qun,Lin Hua,Biville Francis,Xiong Jingyuan,Pei Xiaofang,Zheng Bo,Zou Xiaoli,Wang Chuan
Introduction ClpXP protease is an important proteolytic system in Salmonella enterica serovar typhimurium ( S. typhimurium ). Inactivation of ClpXP by deletion of clpP resulted in overproduction of RpoS and a growth defect phenotype. Only one report has indicated that deleting rpoS can restore the growth of a S. typhimurium clpP mutant to the wild-type level. Whether overproduction of RpoS is responsible for the growth deficiency resulting from clpP disruption and how ClpXP affects the cell metabolism of S. typhimurium remain to be elucidated. Objectives The aim of this study is to investigate the effect of ClpXP on cell metabolism of S. typhimurium and explore the possible co-effect of RpoS associated with ClpXP in cell metabolism. Method We constructed a clpP rpoS double deletion mutant TT-19 (Δ clpP Δ rpoS TT-1) using a two-step phage transduction technique. We then compared the metabolite fingerprints of Salmonella rpoS deletion mutant TT-14 (Δ rpoS TT-1), clpP deletion mutant TT-16 (Δ clpP TT-1), and clpP rpoS double deletion mutant TT-19 (Δ clpP Δ rpoS TT-1) with those of the wild-type strain TT-1 by using gas chromatography coupled with mass spectrometry (GC–MS). Results Deletion of rpoS recovered only a part of the growth of Salmonella clpP mutant. Further metabolome analysis indicated that clpP disruption changed the levels of 16 extra- and 19 intracellular substances, while the extracellular concentrations of 4 compounds (serine, l -5-oxoproline, l -glutamic acid, and l -tryptophan) and intracellular concentrations of 10 compounds ( l -isoleucine, glycine, serine, l -methionine, l -phenylalanine, malic acid, citric acid, urea, putrescine, and 6-hydroxypurine) returned to their wild-type levels when rpoS was also deleted. Conclusion ClpXP affects the cell metabolism of S. typhimurium partially in an RpoS-dependent manner.
研究领域:
微生物学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF BACTERIOLOGY
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2025
·
IF 3
Congjuan Xu,Jie Feng,Yuchen Zhou,Huan Ren,Xiaolei Pan,Shuiping Chen,Xuehua Liu,Guanxian Li,Jinjin Li,Bin Geng,Linlin Gao,Zhihui Cheng,Yongxin Jin,Un-Hwan Ha,Shouguang Jin,Iain L. Lamont,Daniel Pletzer,Weihui Wu
Antibiotic combinations can slow down resistance development and/or achieve synergistic therapeutic effects. In this study, we observed that a combined use of ceftazidime-avibactam (CZA) with azithromycin effectively repressed CZA resistance development in Pseudomonas aeruginosa. Transcriptome analysis revealed that subinhibitory concentrations of azithromycin reduced the expression of genes involved in stress-induced mutagenesis, including the stress response sigma factor rpoS. Interestingly, ribosome profiling revealed global redistribution of ribosomes by azithromycin, among which ribosome stalling was significantly intensified near the 5´ terminus of the rpoS mRNA. Further DNA mutational analysis revealed that azithromycin represses the translation of rpoS through its 5´-terminal rare codons, which in turn reduced its transcription. These in vitro observations have been recapitulated in vivo where azithromycin-repressed CZA resistance development when P. aeruginosa was passaged in mice. Overall, our study revealed the molecular mechanism of azithromycin-mediated repression of antibiotic resistance development, providing a promising antibiotic combination for the treatment of P. aeruginosa infections.
研究领域:
微生物学
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分子生物学
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感染病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
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2024
·
IF 5
Congnan Cen,Xinxuan Wang,Huan Li,Jian Chen,Yanbo Wang
Pseudomonas fluorescens is a spoilage bacterium in food that has the ability to maintain growth and reproduction in high-salt environments. It acts as a defence mechanism through the exclusion of ions and the formation of biofilms. Hence, disrupting this defence mechanism may be a good way to control food spoilage. In this study, a specific flavonoid small molecule baicalin was found, which was able to dismantle the defence mechanism of the bacteria at a lower concentration (400 μM) of treatment. In synergy with salt, baicalin showed a significant inhibitory effect on the growth, c -di-gmp synthetics and biofilm formation of Pseudomonas fluorescens Pf08. Through transcriptomics , we also found that baicalein interfered with bacterial transport and polysaccharide production functions. Through molecular docking and QPCR , we found that baicalin is able to binding with the RpoS protein through hydrogen bonding and thus interfere with its function.
研究领域:
微生物学
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食品科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Processes & Impacts
·
2021
·Vol. 23
·期 7
·995-1005
·
IF 4.238
Qing Ning,Dali Wang,Jing You
Quorum sensing inhibitors (QSIs) are promising alternatives to antibiotics. While QSIs have great application potential in a variety of fields, their joint effects with antibiotics on bacteria, especially on antibiotic resistance mutations, remain largely unexplored. Herein, we report the joint effects of four commonly used antibiotics and two QSIs on bacterial growth and resistance mutations in E. coli. It was found that QSIs presented antagonistic or additive effects with antibiotics on bacterial growth, and more importantly, QSIs exhibited an attenuating effect on antibiotic-induced resistance mutations. Further analysis demonstrated that antibiotics might enhance resistance mutations by promoting the expressions of rpoS, lexA and recA, while QSIs attenuated the mutations by promoting the expressions of mutS and uvrD. The present research provides a comprehensive understanding of the joint effects of antibiotics and QSIs on bacteria, which may benefit the risk assessment of their combined exposure.
研究领域:
微生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2023
·
IF 5.4
Zhuolin Ma,Weiying Xu,Shaoting Li,Siyi Chen,Yuheng Yang,Zefeng Li,Tong Xing,Zepeng Zhao,Dongping Hou,Qingqing Li,Ziying Lu,Hongmei Zhang
Involvement of the transcriptional regulator RpoS in the persistence of viable but non-culturable (VBNC) state has been demonstrated in several species of bacteria. This study investigated the role of the RpoS in the formation and resuscitation of VBNC state in Salmonella enterica serovar Enteritidis CICC 21482 by measuring bacterial survival , morphology, physiological characteristics, and gene expression in wild-type (WT) and rpoS -deletion ( ΔrpoS ) strains during long-term storage in powdered infant formula (PIF). The ΔrpoS strain was produced by allelic exchange using a suicide plasmid. Bacteria were inoculated into PIF for 635-day storage. Survival, morphology, intracellular reactive oxygen species (ROS) levels and intercellular quorum sensing autoinducer-2 (AI-2) contents were regularly measured. Resuscitation assays were conducted after obtaining VBNC cells. Gene expression was measured using real-time quantitative polymerase chain reaction (qPCR). The results showed that RpoS and low temperature conditions were associated with enhanced culturability and recoverability of Salmonella Enteritidis after desiccation storage in low water activity (a w ) PIF. In addition, the synthesis of intracellular ROS and intercellular quorum sensing AI-2 was regulated by RpoS, inducing the formation and resuscitation of VBNC cells. Gene expression of soxS , katG and relA was found strongly associated with RpoS. Due to the lack of RpoS factor, the ΔrpoS strain could not normally synthesize SoxS, catalase and (p)ppGpp, resulting in its early shift to the VBNC state. This study elucidates the role of rpoS in desiccation stress and the formation and resuscitation mechanism of VBNC cells under desiccation stress. It serves as the basis for preventing and controlling the recovery of pathogenic bacteria in VBNC state in low a w foods.
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产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
·
2024
·
IF 11.4
Xiaofeng Han,Long Fu,Jing Yu,Kunting Li,Ziqing Deng,Ruihao Shu,Dali Wang,Jing You,Eddy Y. Zeng
Microplastics (MPs) and antibiotics co-occur widely in the environment and pose combined risk to microbial communities. The present study investigated the effects of erythromycin on biofilm formation and resistance mutation of a model bacterium, E. coli , on the surface of pristine and UV-aged polystyrene (PS) MPs sized 1–2 mm. The properties of UV-aged PS were significantly altered compared to pristine PS, with notable increases in specific surface area, carbonyl index, hydrophilicity, and hydroxyl radical content. Importantly, the adsorption capacity of UV-aged PS towards erythromycin was approximately 8-fold higher than that of pristine PS. Biofilms colonizing on UV-aged PS had a greater cell count (5.6 × 10 8 CFU mg −1 ) and a higher frequency of resistance mutation (1.0 × 10 −7 ) than those on pristine PS (1.4 × 10 8 CFU mg −1 and 1.4 × 10 −8 , respectively). Moreover, erythromycin at 0.1 and 1.0 mg L − 1 significantly ( p < 0.05) promoted the formation and resistance mutation of biofilm on both pristine and UV-aged PS. DNA sequencing results confirmed that the biofilm resistance was attributed to point mutations in rpoB segment of the bacterial genome. qPCR results demonstrated that both UV aging and erythromycin repressed the expression levels of a global regulator rpoS in biofilm bacteria, as well as two DNA mismatch repair genes mutS and uvrD , which was likely to contribute to increased resistance mutation frequency.
研究领域:
环境科学
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微生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·Vol. 27
·期 2
·108818-108818
·
IF 4.6
Manlu Zhu,Haoyan Mu,Xiongfeng Dai
To thrive in nature, bacteria have to reproduce efficiently under favorable conditions and persist during stress. The global strategy that integrates the growth control and stress response remains to be explored. Here, we find that a moderate induction of (p)ppGpp reduces growth rate but significantly enhances the stress tolerance of E. coli , resulting from a global resource re-allocation from ribosome synthesis to the synthesis of stress-responsive proteins. Strikingly, the activation of stress response by (p)ppGpp is still largely retained in the absence of RpoS. In addition, (p)ppGpp induction could activate the catabolism of alanine and arginine, facilitating the adaption of bacteria to nutrient downshift. Our work demonstrates that the activation of stress response by (p)ppGpp could occur in an RpoS-independent manner and (p)ppGpp enables bacteria to integrate the control of growth and stress response in a seesaw fashion, thus acting as an important global regulator of the bacterial fitness landscape.
研究领域:
微生物学
·
分子生物学
·
细菌学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）