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

Abstract Staphylococcus aureus is 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 in S. aureus mecA+. Understanding S. aureus virulence determinants will help develop anti-virulence strategies, especially given the lack of an anti- S. aureus vaccine and rising antibiotic resistance. Highlights Complex 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 the mecA gene. Molecular analysis revealed distinct expression patterns, notably elevated spA and atlA expression, in mecA + strains. Negative correlation with RNAIII : Our findings indicate a negative correlation between RNAIII regulator expression and the mecA gene 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 and mecA gene transcription in S. aureus mecA + strains.