Burkholderia cenocepacia and Pseudomonas aeruginosa coinfection alters antimicrobial tolerance, infection dynamics and host immune effectiveness

Polymicrobial infections promote the appearance of a network of interactions that can lead to an increase in their antimicrobial tolerance or to the evasion of the host immune system. Pseudomonas aeruginosa and Burkholderia cenocepacia are two multidrug-resistant opportunistic pathogens that significantly influence host health and alter their antibiotic response when in coinfection. To characterize host-pathogen dynamics, we examined infection progression, immune responses, bacterial virulence gene expression, and antibiotic susceptibility in single and coinfections involving acute and chronic P. aeruginosa strains combined with B. cenocepacia. This work was entirely performed in vivo using G. mellonella larvae as a model. Larval survival and bacterial dissemination were monitored, revealing tissue-specific patterns of infection. Our findings indicated that coinfections increased larval lethality and worsened overall health. Notably, B. cenocepacia suppressed host melanization and immune responses, while P. aeruginosa triggered a strong immune activation. Coinfection also induced upregulation of virulence genes in both pathogens. Surprisingly, increased antibiotic susceptibility was observed in coinfected groups compared to single infections. This study advances understanding of host-pathogen interactions in polymicrobial infections and highlights the need for improved therapeutic strategies. Author summaryBacterial coinfections, such as the ones with Pseudomonas aeruginosa and Burkholderia cenocepacia are especially critical in chronic lung diseases like cystic fibrosis, where persistent polymicrobial infections drive lung damage and health decline. Coinfection can enhance pathogen survival, increase drug tolerance, and disrupt host immunity, leading to worse clinical outcomes. Understanding coinfection dynamics can help improve treatment strategies, optimize antibiotic use and improve infection monitorization. Therefore, by studying and understanding microbial interactions, researchers can develop more effective therapies, ultimately improving patient care and combating the growing challenge of multidrug-resistant bacterial infections.