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转录组学揭示酸适应侵袭性非产碳青霉烯酶肺炎克雷伯菌13719中多粘菌素耐药机制

Mechanisms of Polymyxin Resistance in Acid-Adapted Enteroinvasive NCCP 13719 Revealed by Transcriptomics.

作者信息

Hwang Daekeun, Kim Hyun Jung

机构信息

Korea Food Research Institute, Wanju 55365, Republic of Korea.

Department of Food Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea.

出版信息

Microorganisms. 2024 Dec 11;12(12):2549. doi: 10.3390/microorganisms12122549.

DOI:10.3390/microorganisms12122549
PMID:39770753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11677122/
Abstract

Acid adaptation in can induce antimicrobial resistance (AMR), posing challenges to global public health. We investigated the effects of acid adaptation on antimicrobial susceptibility, gene expression, zeta potential, and the outer membrane (OM) properties of NCCP 13719. The acid-adapted (AA) strain exhibited increased resistance to multiple antimicrobials, with minimum inhibitory concentrations for colistin and polymyxin B increasing eight- and two-fold, respectively. Transcriptomic analysis identified 2225 differentially expressed genes, including upregulated genes associated with resistance to cationic antimicrobial peptides such as , , and . The upregulation of the operon suggests modifications in lipid A of lipopolysaccharides (LPS), reducing the negative charge of the OM and decreasing polymyxin binding affinity. Zeta potential measurements indicated a shift toward a less negative surface charge in the AA strain, which is consistent with LPS modifications. The AA strain also showed decreased OM permeability, which correlated with increased resistance to antimicrobials that penetrate the OM. These mechanisms collectively diminish the efficacy of polymyxins and highlight the potential for environmental factors to drive antimicrobial resistance. In conclusion, the acid adaptation of NCCP 13719 enhances AMR through changes in gene expression and OM modifications, highlighting the need for careful control of acidic environments during the treatment of medical devices and wastewater from food processing to prevent the emergence of resistant strains.

摘要

[具体细菌名称]中的酸适应可诱导抗菌药物耐药性(AMR),给全球公共卫生带来挑战。我们研究了酸适应对[具体细菌名称] NCCP 13719的抗菌药物敏感性、基因表达、zeta电位和外膜(OM)特性的影响。酸适应(AA)菌株对多种抗菌药物的耐药性增加,对黏菌素和多黏菌素B的最低抑菌浓度分别增加了8倍和2倍。转录组分析确定了2225个差异表达基因,包括与对阳离子抗菌肽(如[具体基因名称1]、[具体基因名称2]和[具体基因名称3])耐药相关的上调基因。[具体操纵子名称]操纵子的上调表明脂多糖(LPS)的脂质A发生了修饰,降低了外膜的负电荷并降低了多黏菌素的结合亲和力。Zeta电位测量表明AA菌株的表面电荷向负性较小的方向转变,这与LPS修饰一致。AA菌株还表现出外膜通透性降低,这与对穿透外膜的抗菌药物耐药性增加相关。这些机制共同降低了多黏菌素的疗效,并突出了环境因素驱动抗菌药物耐药性的可能性。总之,[具体细菌名称] NCCP 13719的酸适应通过基因表达变化和外膜修饰增强了AMR,凸显了在医疗器械处理和食品加工废水处理过程中仔细控制酸性环境以防止耐药菌株出现的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/2296ffda755e/microorganisms-12-02549-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/e212e15afb62/microorganisms-12-02549-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/669ded279ccc/microorganisms-12-02549-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/ddca440618ee/microorganisms-12-02549-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/2296ffda755e/microorganisms-12-02549-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/e212e15afb62/microorganisms-12-02549-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/669ded279ccc/microorganisms-12-02549-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/ddca440618ee/microorganisms-12-02549-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aea9/11677122/2296ffda755e/microorganisms-12-02549-g004.jpg

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