Overview: Intermicrobial Dynamics in COPD-Associated Infections
Microbial communities shape the flow of energy and matter in chronic infections. In conditions like chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), polymicrobial communities often drive virulence and antibiotic resistance. This study focuses on the interaction between two airway-associated microbes, Pseudomonas aeruginosa and Streptococcus salivarius, isolated from COPD patients, and examines how antibiotic treatment—specifically aztreonam—recalibrates their relationship.
Key Players: P. aeruginosa, S. salivarius, and Quorum Sensing
P. aeruginosa is a dominant opportunistic pathogen with a robust quorum-sensing (QS) system that regulates virulence factors such as pyocyanin and elastases. S. salivarius, a commensal oral bacterium increasingly recognized as a lung microbiome resident, can modulate the environment through extracellular products that influence P. aeruginosa virulence. The study investigates two strain pairs from COPD patients: a lasR-intact P. aeruginosa (PAcx1) with its S. salivarius partner (SScx1), and a lasR-mutant P. aeruginosa (PAcx2) with its S. salivarius partner (SScx2).
Aztreonam’s Sub-Inhibitory Effects and Interbacterial Interactions
Aztreonam, a β-lactam antibiotic, was applied at sub-inhibitory concentrations to explore its impact on interspecies dynamics rather than solely on growth inhibition. Findings show that while S. salivarius growth remains largely unaffected at 8 µg/mL, P. aeruginosa experiences delayed initial growth, yet can rebound in monoculture. Remarkably, in the presence of aztreonam, S. salivarius gains a competitive edge, invading P. aeruginosa more effectively than in antibiotic-free conditions. This shift underscores how antibiotics influence microbial interactions beyond simple susceptibility.
Dynamic Competition Under Antibiotic Pressure
Using dynamic competition assays, researchers tracked the P. aeruginosa to S. salivarius ratio over 24 hours. Without antibiotics, P. aeruginosa generally outcompetes S. salivarius, consistent with QS-driven virulence. The introduction of sub-MIC aztreonam reverses this pattern: S. salivarius can overtake P. aeruginosa across various initial ratios. The finding suggests that aztreonam modulates signaling and metabolic pathways, reshaping interspecies competition and potentially reducing disease severity in polymicrobial infections.
Transcriptomic Shifts Under Cross-Feeding and Aztreonam
In cross-feeding setups that physically separate the species but allow exchange of metabolites, aztreonam activates S. salivarius gene expression while suppressing P. aeruginosa QS and metabolism. RNA sequencing reveals substantial downregulation of QS genes (lasR, rhlR, mvfR, pqsH) and pyocyanin biosynthesis pathways in P. aeruginosa under co-culture with S. salivarius and aztreonam. Conversely, S. salivarius upregulates growth and biosynthetic pathways, enabling it to counteract P. aeruginosa dominance during antibiotic exposure.
Virulence Modulation and Host-Relevant Outcomes
Extracellular products from S. salivarius significantly dampen P. aeruginosa virulence factors, notably pyocyanin production, with stronger effects observed in lasR-mutant strains. qPCR confirms downregulation of QS genes in P. aeruginosa when exposed to S. salivarius supernatants, and this suppression is amplified in the presence of aztreonam. A Caenorhabditis elegans infection model further supports these results: aztreonam and S. salivarius metabolites together reduce P. aeruginosa lethality toward nematodes, suggesting potential therapeutic benefits from exploiting microbial interactions in polymicrobial COPD infections.
Implications for COPD and Polymicrobial Infections
These findings highlight that antibiotic interventions can recalibrate interbacterial interactions, not just kill susceptible bacteria. In COPD and other chronic lung diseases, where oral microbiota contribute to the lung ecosystem, aztreonam may indirectly suppress P. aeruginosa virulence by empowering beneficial interspecies relationships mediated by S. salivarius. This supports a shift in thinking from mono-species targets to ecosystem-aware strategies in managing polymicrobial infections and antibiotic resistance.
Conclusion
Aztreonam at sub-inhibitory levels can flip the competitive balance between P. aeruginosa and S. salivarius, promoting S. salivarius’s antagonistic effects on P. aeruginosa QS and virulence. The dual impact—enhanced S. salivarius activity and dampened P. aeruginosa virulence—emerges most clearly in co-culture and cross-feeding conditions. These insights pave the way for therapeutic approaches that consider polymicrobial ecology in COPD and other chronic respiratory infections.
