Emerging insights into the growing phenomenon of bacterial co-infections

In the realm of complex infectious diseases, the intruders are frequently polymicrobial, involving multiple infectious agents. However, our understanding of the profound impact these microbial communities exert on the progression of infections, leading to significant morbidity and mortality, remains limited. Moreover, bacterial co-infections can contribute to heightened antimicrobial resistance and antibiotic tolerance.

In our investigation of polymicrobial infections, we focus on two opportunistic pathogens: Pseudomonas aeruginosa and Staphylococcus aureus. These microorganisms are commonly co-isolated from chronic wounds and the sputum of cystic fibrosis patients. Despite their prevalence, the interplay between these pathogens in co-culture settings has yielded disparate findings in recent years.

Our research delves into the intricate dynamics of this relationship, examining strains that either coexist harmoniously or exert harm upon each other. By unraveling the complexities of P. aeruginosa and S. aureus co-cultures, we aim to shed light on the nuanced interactions that influence the course of infections, with implications for understanding morbidity, mortality, and the emergence of antibiotic resistance.

Image credit: Deborah Yung (and check out more of her designs here: @Debz_microart) [1]

Utilising polymicrobial infection models for investigating drug efficacy

A comprehensive understanding of the intricate mechanisms governing complex polymicrobial infections is currently lacking. Our research endeavors aim to illuminate these biological processes through the examination of polymicrobial communities both in vitro and in vivo, specifically in the context of skin and lung infections.

We have innovatively developed a Pseudomonas-Staphylococcus co-culture biofilm model within host-mimicking conditions. Additionally, we employ a novel murine cutaneous abscess model to scrutinize their interactions and monitor changes in susceptibility to antibiotics and novel drug compounds.

In exploring the antagonistic behavior between these pathogens, we employ transposon mutants to dissect the molecular players involved in their mutual killing mechanisms.

Expanding beyond our primary model organisms, we extend our investigations to co-cultures involving prevalent human skin and lung pathogens, including Staphylococcus, Enterococcus, Cutibacterium, Klebsiella, and Acinetobacter. This broadened scope enhances our understanding of the complex dynamics at play in polymicrobial infections.

How do polymicrobial infections alter the immune response?

We delve into pivotal questions, examining the impact of microbial interactions on immune responses, understanding the collective contribution of multiple microbes to disease progression, and exploring effective treatment strategies for infectious diseases.

Our research employs a dual-pronged methodology. Firstly, we investigate how the pathogenic traits of one bacterium may undergo alteration, either through direct interaction with another bacterium or indirectly through the activation and modulation of alternative host responses. Secondly, we scrutinize the effects of polymicrobial colonization and exposure, aiming to unravel the induction of distinct host immune response pathways and their influence on the trajectory of disease progression.