NWMN2330 May Be Associated with the Virulence of Staphylococcus aureus by Increasing the Expression of hla and saeRS

Abstract

Introduction: Staphylococcus aureus 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 S. aureus 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 S. aureus infections. Results: In this study, we constructed a NWMN2330 deletion mutant (Newman-ΔNWMN2330) and a complement (Newman-ΔNWMN2330-C) of S. aureus Newman to study the role of NWMN2330 in the virulence of S. aureus. Through transcriptome sequencing, it was found that the expression of 224 genes in Newman-ΔNWMN2330 was significantly different (>2-fold) compared with S. aureus Newman, and these differentially expressed genes were related to multiple functions of S. aureus. And we found that NWMN2330 could positively regulate the expression of S. aureus hla gene. Therefore, the deletion mutant Newman-ΔNWMN2330 exhibited lower hemolytic activity and lower α-toxin production than Newman. Newman-ΔNWMN2330 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 saeRS and hla in Newman-ΔNWMN2330 strain was significantly reduced at the mRNA level, which preliminarily indicated that NWMN2330 promoted the expression of hla by up-regulating saeRS. Discussion: In general, our results indicated that NWMN2330 may be associated with the virulence of Staphylococcus aureus by increasing the expression of hla and saeRS.