Li Bin, Ge Mengyu, Zhang Yang, Wang Li, Ibrahim Muhammad, Wang Yanli, Sun Guochang, Chen Gongyou
State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, 310058, Hangzhou, China.
Department of Biosciences, COMSATS Institute of Information technology Sahiwal Campus, Sahiwal, Pakistan.
Sci Rep. 2016 Feb 26;6:22241. doi: 10.1038/srep22241.
Recent research has shown that pathogen virulence can be altered by exposure to antibiotics, even when the growth rate is unaffected. Investigating this phenomenon provides new insights into understanding the virulence mechanisms of bacterial pathogens. This study investigates the phenotypic and transcriptomic responses of the rice pathogenic bacterium Acidovorax avenae subsp. avenae (Aaa) strain RS-1 to ß-lactam antibiotics especially Ampicillin (Amp). Our results indicate that exposure to Amp does not influence bacterial growth and biofilm formation, but alters the virulence, colonization capacity, composition of extracellular polymeric substances and secretion of Type VI secretion system (T6SS) effector Hcp. This attenuation in virulence is linked to unique or differential expression of known virulence-associated genes based on genome-wide transcriptomic analysis. The reliability of expression data generated by RNA-Seq was verified with quantitative real-time PCR of 21 selected T6SS genes, where significant down-regulation in expression of hcp gene, corresponding to the reduction in secretion of Hcp, was observed under exposure to Amp. Hcp is highlighted as a potential target for Amp, with similar changes observed in virulence-associated phenotypes between exposure to Amp and mutation of hcp gene. In addition, Hcp secretion is reduced in knockout mutants of 4 differentially expressed T6SS genes.
最近的研究表明，即使生长速率未受影响，病原体的毒力也可因接触抗生素而改变。对这一现象的研究为理解细菌病原体的毒力机制提供了新的见解。本研究调查了水稻病原菌燕麦嗜酸菌燕麦亚种（Aaa）RS-1菌株对β-内酰胺类抗生素尤其是氨苄青霉素（Amp）的表型和转录组反应。我们的结果表明，接触氨苄青霉素不会影响细菌生长和生物膜形成，但会改变毒力、定殖能力、胞外聚合物的组成以及VI型分泌系统（T6SS）效应蛋白Hcp的分泌。基于全基因组转录组分析，这种毒力的减弱与已知毒力相关基因的独特或差异表达有关。通过对21个选定的T6SS基因进行定量实时PCR验证了RNA测序产生的表达数据的可靠性，在接触氨苄青霉素的情况下，观察到hcp基因表达显著下调，这与Hcp分泌的减少相对应。Hcp被突出显示为氨苄青霉素的潜在靶点，在接触氨苄青霉素和hcp基因突变之间观察到毒力相关表型有类似变化。此外，在4个差异表达的T6SS基因的敲除突变体中，Hcp分泌减少。
