Burkholderia cenocepacia and Pseudomonas aeruginosa coinfection increases host mortality by altering infection dynamics and compromising 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 antibiotic responses when coinfected. To characterize host-pathogen dynamics, we examined infection progression, immune responses, bacterial virulence gene expression, global transcriptomic analysis, and antibiotic susceptibility in single and coinfections involving acute and chronic P. aeruginosa strains combined with B. cenocepacia. This work was 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 host 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. This study advances understanding of host-pathogen interactions in polymicrobial infections and highlights the need for improved therapeutic strategies.