布鲁氏菌 melitensis NI 对多黏菌素 B 反应的全基因组分析

Genome-Wide Analysis of the Response of Brucella melitensis NI to Polymyxin B.

机构信息

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, China.

State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

出版信息

Curr Pharm Biotechnol. 2021 Oct 6;22(14):1891-1899. doi: 10.2174/1389201021666201218125148.

DOI:10.2174/1389201021666201218125148

PMID:33342409

Abstract

BACKGROUND

The ability of pathogenic bacteria to survive Antimicrobial Peptides (AMPs) in various host niches may contribute to their virulence. Polymyxin B is a cationic AMP, and polymyxin drugs are considered to be the "last line of defense" in the clinical treatment of bacterial infections.

OBJECTIVE

The objectives of this study were to comprehensively study the response of Brucella melitensis strain NI to polymyxin B treatment and to identify the target genes in Brucella induced by polymyxin B stimulation.

METHODS

Following treatment with polymyxin B, differentially expressed genes in Brucella were detected using RNA-seq and validated using qRT-PCR.

RESULTS

In total, 874 differentially expressed genes were identified, including 560 up-regulated and 314 down-regulated genes. Functional annotation and KEGG pathway analysis revealed that many of these genes are involved in metabolism, two-component systems, transcriptional regulation, transport/ membrane proteins, and virulence factors. Expression of genes involved in T4SS and flagellar biosynthesis and assembly, which are important virulence factors in Brucella, were up-regulated by polymyxin B treatment.

DISCUSSION

Additionally, genes encoding the ABC transporters YejABEF and the cold-shock protein CspA were also up-regulated. These genes confer resistance to AMPs and contribute to the virulence of Brucella. The NIΔsufC, NIΔsufD, NIΔompW, NIΔexbB, NIΔtetR, and NIΔcspA mutants were also more sensitive than B. melitensis NI to polymyxin B.

CONCLUSION

The results of this study provide important insights into the comprehensive response of Brucella in response to polymyxin B stimulation.

摘要

背景

在各种宿主小生境中，致病菌对抗菌肽（AMPs）的生存能力可能与其毒力有关。多粘菌素 B 是一种阳离子 AMP，多粘菌素类药物被认为是治疗细菌感染的“最后一道防线”。

目的

本研究旨在全面研究布鲁氏菌 melitensis 菌株 NI 对多粘菌素 B 治疗的反应，并鉴定多粘菌素 B 刺激布鲁氏菌诱导的靶基因。

方法

用多粘菌素 B 处理后，用 RNA-seq 检测布鲁氏菌中差异表达的基因，并通过 qRT-PCR 进行验证。

结果

共鉴定出 874 个差异表达基因，其中 560 个上调，314 个下调。功能注释和 KEGG 通路分析表明，这些基因涉及代谢、双组分系统、转录调控、转运/膜蛋白和毒力因子。多粘菌素 B 处理后，T4SS 和鞭毛生物合成和组装相关基因的表达上调，这些基因是布鲁氏菌的重要毒力因子。

讨论

此外，编码 ABC 转运体 YejABEF 和冷休克蛋白 CspA 的基因也上调。这些基因赋予 AMP 抗性，并有助于布鲁氏菌的毒力。NIΔsufC、NIΔsufD、NIΔompW、NIΔexbB、NIΔtetR 和 NIΔcspA 突变体对多粘菌素 B 的敏感性也高于 B. melitensis NI。