Liu Li, Wang Bingjie, Yu Jingyi, Guo Yinjuan, Yu Fangyou
Department of Transfusion Medicine, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, People's Republic of China.
Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Infect Drug Resist. 2022 Jun 2;15:2853-2864. doi: 10.2147/IDR.S365314. eCollection 2022.
is an opportunistic pathogen that can cause life-threatening bloodstream infections such as sepsis and endocarditis. In recent years, the emergence and increase of methicillin-resistant and multidrug-resistant has posed a great challenge to the antibiotic treatment of infectious diseases. Anti-virulence strategies targeting virulence factors are an effective new therapy for the treatment of infections.
In this study, we constructed a deletion mutant () and a complement () of to study the role of in the virulence of . Through transcriptome sequencing, it was found that the expression of 224 genes in was significantly different (>2-fold) compared with Newman, and these differentially expressed genes were related to multiple functions of . And we found that could positively regulate the expression of gene. Therefore, the deletion mutant exhibited lower hemolytic activity and lower α-toxin production than also exhibited lower lethality and pathogenicity in worm survival experiments and nude mouse skin abscess model. RT-qPCR results showed that compared with the wild-type strain, the expression of and in strain was significantly reduced at the mRNA level, which preliminarily indicated that promoted the expression of by up-regulating .
In general, our results indicated that may be associated with the virulence of by increasing the expression of and
是一种机会致病菌,可引起危及生命的血流感染,如败血症和心内膜炎。近年来,耐甲氧西林和多重耐药的出现及增加,给传染病的抗生素治疗带来了巨大挑战。针对毒力因子的抗毒力策略是治疗感染的一种有效的新疗法。
在本研究中,我们构建了的缺失突变体()和互补体(),以研究在毒力中的作用。通过转录组测序发现,与纽曼菌株相比,中有224个基因的表达存在显著差异(>2倍),这些差异表达基因与的多种功能相关。并且我们发现可正向调控基因的表达。因此,缺失突变体的溶血活性和α毒素产生量均低于,在蠕虫存活实验和裸鼠皮肤脓肿模型中也表现出较低的致死率和致病性。RT-qPCR结果表明,与野生型菌株相比,菌株中及在mRNA水平上的表达显著降低,这初步表明通过上调促进了的表达。
总体而言,我们的结果表明,可能通过增加和的表达与的毒力相关