Burkholderia cenocepaciaandPseudomonas aeruginosacoinfection 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 aeruginosaandBurkholderia cenocepaciaare 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 chronicP. aeruginosastrains combined withB. cenocepacia. This work was entirely performedin vivousingG. mellonellalarvae 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. cenocepaciasuppressed host melanization and immune responses, whileP. aeruginosatriggered 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.