Poster Presentation 14th Lorne Infection and Immunity 2024

Investigating antimicrobial activity in the human gastrointestinal microbiome (#149)

Jamia Hemphill 1 2 , Jodee Gould 1 3 , Marina Yakou 1 , Cristina Giogha 1 2 , Rhys Dunstan 2 , Sarah Larcombe 2 , Heidi Yu 2 , Jian Li 2 , Dena Lyras 2 , Trevor Lithgow 2 , Elizabeth Hartland 1 2 , Emily Gulliver 1 3 , Samuel Forster 1 3
  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia
  2. Department of Microbiology, Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
  3. Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia

Antimicrobial resistance is rapidly increasing across the globe, driving the need for novel therapeutics to treat bacterial pathogens. In microbial communities, some bacterial species produce antimicrobial molecules to gain competitive advantage, and thereby present a promising source of new antimicrobial therapeutic agents. Antimicrobials produced by the gut microbiota and the role they play within commensal communities remains poorly understood due to difficulties in culturing the fastidious anaerobic gut microbes.

However, with recent advances in culturing techniques, alongside analysis of metagenomic data, antimicrobial production in the gut microbiome can be further investigated. In this study, we have demonstrated that members of the human gut microbiota have inhibitory effects against multi-drug resistant gastrointestinal pathogens due to the production of antimicrobial molecules. Using high throughput culturing methods, a panel of human gastrointestinal microbiota isolates were screened for antimicrobial activity against eight multi-antimicrobial resistant strains of gastrointestinal pathogens: Clostridiodes difficile, Escherichia coli, Enterococcus faecium, and Klebsiella pneumoniae. Of the 287 bacterial isolates screened, 148 (52%) exhibited inhibition of at least one of the pathogens. From these isolates, candidates that displayed inhibition of at least three of the four pathogens were selected for genomic screening. Genes with a high similarity (>90%) to known antimicrobial genes were identified in 4 of the 20 candidates. To confirm if the inhibitory phenotype of these candidates was due to antimicrobial production, an Enterolysin A gene from a commensal Enterococcus sp. strain was successfully expressed in an E. coli BL21 C43 strain, where it demonstrated inhibition of the E. faecium pathogens. Further investigation into the action of this antimicrobial when in a community of commensal bacteria may provide valuable insight into how gut microbiome-derived antimicrobial therapies can be leveraged to prevent and treat antimicrobial resistant gastrointestinal infections.