| Summary: | <i>Staphylococcus aureus</i> expresses diverse proteins at different stages of growth. The immunodominant staphylococcal antigen A (IsaA) is one of the proteins that is constitutively produced by <i>S. aureus</i> during colonisation and infection. SACOL2584 (or <i>isaA</i>) is the gene that encodes this protein. It has been suggested that IsaA can hydrolyse cell walls, and there is still need to study <i>isaA</i> gene disruption to analyse its impact on staphylococcal phenotypes and on alteration to its transcription and protein profiles. In the present study, the growth curve in RPMI medium (which mimics human plasma), autolytic activity, cell wall morphology, fibronectin and fibrinogen adhesion and biofilm formation of <i>S. aureus</i> SH1000 (wildtype) was compared to that of <i>S. aureus</i> MS001 (<i>isaA</i> mutant). RNA sequencing and liquid chromatography–tandem mass spectrometry were carried out on samples of both <i>S. aureus</i> strains taken during the exponential growth phase, followed by bioinformatics analysis. Disruption of <i>isaA</i> had no obvious effect on the growth curve and autolysis ability or thickness of cell walls, but this study revealed significant strength of fibronectin adherence in <i>S. aureus</i> MS001. In particular, the <i>isaA</i> mutant formed less biofilm than <i>S. aureus</i> SH1000. In addition, proteomics and transcriptomics showed that the adhesin/biofilm-related genes and hemolysin genes, such as <i>sasF</i>, <i>sarX</i> and <i>hlgC</i>, were consistently downregulated with <i>isaA</i> gene disruption. The majority of the upregulated genes or proteins in <i>S. aureus</i> MS001 were <i>pur</i> genes. Taken together, this study provides insight into how <i>isaA</i> disruption changes the expression of other genes and has implications regarding biofilm formation and biological processes.
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