The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections.

IF 3.9 2区医学 Q1 INFECTIOUS DISEASES

Journal of Antimicrobial Chemotherapy Pub Date : 2024-10-04 DOI:10.1093/jac/dkae355

Lifei Yu, Xinhong Han, Wang Zhang, Ying Fu, Shaoxue Yang, Shenghai Wu, Jie Jin, Siying Li, Yan Chen, Yan Jiang, Yunsong Yu

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引用次数: 0

Abstract

Objectives: To assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).

Methods: Five S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT-PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.

Results: WGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.

Conclusions: These findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.

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双组分传感因子 envZ 在引起多部位侵袭性感染的耐多药肠炎沙门氏菌的进化动态中影响抗生素耐药性和毒力。

目的评估双组分传感器 envZ 的突变对 MDR 肠炎沙门氏菌（S. enteritidis）进化动态中抗生素耐药性和毒力的影响：方法：分析了从一名多部位侵袭性感染患者体内分离出的五株肠炎沙门氏菌。通过 WGS 对抗生素耐药基因、毒力基因和 SNP 进行了分析。利用 RNA 测序、定量 RT-PCR、Galleria mellonella（G. mellonella）感染模型毒力测试和体外细胞实验来研究 envZ 突变的影响：结果：WGS 发现所有菌株中的 IncFIB(S)/IncFII(S)/IncX1 融合质粒上都有相同的抗性和毒力基因。粪便菌株携带 envZ 突变，降低了外膜蛋白 ompD 和 ompF 的转录水平。毒力测试表明，envZ 突变菌株的毒力增强。体外实验显示，envZ 突变株的粘附性、侵袭性和抗吞噬性增强，生物膜形成和生长速度降低：这些发现突显了 envZ 上影响临床肠炎球菌菌株抗生素耐药性和毒力的新基因位置。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Antimicrobial Chemotherapy 医学-传染病学

CiteScore

9.20

自引率

5.80%

发文量

423

审稿时长

2-4 weeks

期刊介绍： The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.