Pseudomonas aeruginosa modulates Staphylococcus aureus biofilm formation and antibiotic resistance

This study investigated how co-existence between bacterial species affect virulence and antimicrobial resistance of each other. The effects of co-culturing with Pseudomonas aeruginosa ( P. aeruginosa ) on Staphylococcus aureus ( S. aureus ) virulence and survival under sub-MIC antibiotic exposure were assessed in vitro using 12 bacterial combinations. These combinations were divided into three groups: standard, co-isolated (from the same patient), and random combinations. The effect of these interactions on pathogenicity was also evaluated using a mouse model. Co-culture significantly enhanced S. aureus survival following exposure to azithromycin (100%), gentamicin (91.7%), cefepime (91.7%) and ciprofloxacin (58.3%). Likewise, biofilm formation and clot lysis activity were significantly enhanced in 83% and 67% mixtures, respectively. Gene expression analysis revealed significant upregulation of icaD and sspA in 100% and 89% of the tested combinations, respectively, compared with mono-culture. Overall, the results demonstrate an interspecies interaction between the two pathogens which increased antimicrobial tolerance and virulence in S. aureus . Consistent with these findings, co-infected mice exhibited higher mortality rates and elevated bacterial counts in lung and liver tissues. Taken together, these findings highlight the effect of polymicrobial interactions in evaluating bacterial pathogenicity and resistance to antimicrobial agents.