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.
Keywords: virulence, NWMN2330 , Staphylococcus aureus , hla , saeRS