Oral Presentation BacPath 2024

Investigating Cooperative Relationships between A. baumannii and ESKAPEE Pathogens (#53)

Jasmine M Williams 1 , Hannah Lott 1 , Jocelyn Johns 2 , Ian T Paulsen 1 2 , Aidan Tay 1 , Ram P Maharjan 1 , Amy K Cain 1
  1. ARC Centre of Excellence in Synthetic Biology, School of Natural Sciences, Macquarie University, Sydney, NSW, Australia
  2. Australian Genome Foundry, Macquarie University, Sydney, NSW, Australia

Antibiotic resistance is a major public health concern that is rapidly accelerating towards a 2050 projection of 10 million deaths occurring annually. The World Health Organization has flagged critical bacterial species urgently in need of new therapeutics, including the leading cause of hospital infections, the ‘ESKAPEE’ pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli). Previously we demonstrated that co-infections of A. baumannii and K. pneumoniae worked co-operatively to provide antibiotic cross resistance and heightened virulence. In this study, we investigated the polymicrobial nature of A. baumannii engaging more broadly in cooperative relationships with ESKAPEE pathogens to increase resistance and virulence during infection-relevant conditions. For this we designed a high-throughput unbiased screening methodology to test 240 combinations of clinical ESKAPEE isolates and A. baumannii. We examined co-cultures in a range of clinically relevant conditions including using rich media, antibiotic supplemented rich media, synthetic lung mimicking media, iron deficient media, and human serum. Co-cultures were also screened for communal behaviours in competition plate assays, antibiotic cross-protection and antibiotic disk diffusion assessments, and in vivo virulence ability. Overall, increased antibiotic resistance and virulence traits were observed for most co-culture combinations, with K. pneumoniae, S. aureus and E. faecium, each displaying the clearest synergistic behaviours with A. baumannii, while P. aeruginosa showed the least synergism. Furthermore, large-scale genomic analyses revealed that these microbial combinations are present in many whole genome sequencing datasets. The outcomes of this research will inform optimisation of coinfection treatment strategies, diagnosis, and hospital infection management, ultimately minimising patient deaths.