Impact of methicillin resistance on virulence factor expression inStaphylococcus aureus: Insights from gene expression profiling

AbstractStaphylococcus aureusis a major human pathogen causing various clinical infections and a leading cause of morbidity and mortality worldwide. S. aureus infections are problematic due to frequent antibiotic resistance, especially to methicillin. This study investigated 30 unduplicated S. aureus strains from clinical samples to establish a link between methicillin resistance and virulence factors.We detected and determined expression levels of the mecA gene, virulence genes (spdC, spA, atlA), and the RNAIII regulator using qRT-PCR. All virulence genes and the RNAIII regulator were detected in all strains. Phenotypic results showed only three strains (10%) were methicillin-resistant, while 12 (40%) carried the mecA gene. mecA-positive strains exhibited high expression of adhesion factors (spA) and biofilm formation factors (atlA), but low expression of the RNAIII regulator. The regulator’s expression was negatively correlated with mecA gene expression. Using a multilayer association network, we found a correlation between phenotypic methicillin resistance expression and mecA gene transcription inS. aureusmecA+. UnderstandingS. aureusvirulence determinants will help develop anti-virulence strategies, especially given the lack of an anti-S. aureusvaccine and rising antibiotic resistance.HighlightsComplex interplay between methicillin resistance and virulence:Our study unveils a complex interplay between methicillin resistance and the expression of virulence genes in Staphylococcus aureus clinical isolates.Phenotypic and molecular correlation:Phenotypic resistance to methicillin was observed in only 10% of the isolates, whereas 40% carried themecAgene. Molecular analysis revealed distinct expression patterns, notably elevatedspAandatlAexpression, inmecA+strains.Negative correlation withRNAIII:Our findings indicate a negative correlation betweenRNAIIIregulator expression and themecAgene in the same strains, shedding light on their regulatory relationship.Multilayer association network:Utilizing a multilayer association network, we established a correlation between phenotypic methicillin resistance andmecAgene transcription inS. aureus mecA+strains.