Abstract
BACKGROUND: Polymicrobial infections are recognized as a direct cause of exacerbation in chronic respiratory infections. In patients with reduced lung function, the transfer of oral microbiota to the lungs is often higher than in healthy individuals. However, the mechanisms underlying the interaction between dominant pathogens and oral microbiota, as well as their relationship with antibiotics, remain poorly understood. Using Pseudomonas aeruginosa and Streptococcus salivarius, co-isolated from the bronchial fluid of chronic obstructive pulmonary disease (COPD) patients, as a model, we investigated their interspecies invasion dynamics under antibiotic intervention. This study employed a combination of phenotypic and transcriptomic analyses to elucidate interaction dynamics under antibiotic intervention, providing insight into the gene expression and virulence impacts of antibiotics during co-infection. RESULTS: Our findings revealed that P. aeruginosa significantly inhibited the growth of S. salivarius on blank agar plates. However, in the presence of the β-lactam antibiotic aztreonam, at a sub-inhibitory concentration, the quorum sensing (QS) system of P. aeruginosa was suppressed, and genes related to growth and metabolism were downregulated. Conversely, the intervention of aztreonam activated S. salivarius in co-culture, enabling its successful invasion of P. aeruginosa. Although S. salivarius exhibited inhibitory activity against P. aeruginosa, antibiotic intervention played a critical role in reversing their inherent competitive relationship. CONCLUSION: This study suggests that the repeated use of antibiotics may contribute to the persistent coexistence of polymicrobial communities within the host, leading to complex microbial dynamics that impact disease progression. It underscores the critical need to explore bacterial interactions in detail, as understanding these relationships could revolutionize our approach to chronic diseases caused by polymicrobial infections, offering new therapeutic strategies that go beyond traditional pathogen-targeted treatments.