Characterization and Expression of Drug Resistance Genes in Multidrug Resistance Organisms (MDROs) Originating from Combat Wound Infections

Antimicrobial resistance in bacterial pathogens is steadily increasing and recognized as one of the greatest threats to global public health. This is of particular concern to the Military Health System since recent wars in Afghanistan and Iraq resulted in a major spike in the number of wound and healthcare-acquired infections by bacteria resistant to three or more antibiotics (i.e. multi-drug resistant organisms, or MDROs).

This study used advanced genomic and bioinformatics approaches coupled to cell culturing to identify and characterize factors that influence virulence (including antibiotic resistance, and biofilm formation) in MDROs. This objective has been accomplished through experiments focusing on the regulatory responses of both target and challenger organisms in bacterial-bacterial and bacterial-eukaryotic interactions likely to occur in the wound environment. Deep next-generation cDNA sequencing was used as a tool to dissect the regulatory networks altered during these organismal-level confrontations. Cell-cell challenges include: MDROs versus human skin commensal organisms, MDROs versus other MDROs, and MDROs versus cultured human fibroblasts.

Our results showed that specific interacting partners could impose a negative effect on MDRO virulence, while other interactors induced the expression of genes involved in virulence including antimicrobial resistance genes (AMRs). This project was carried out in collaboration with the Walter Reed Army Institute of Research Multidrug-resistant Organism Repository and Surveillance Network (WRAIR MRSN), who have provided isolates of highest clinical importance collected from military health care facilities. The research outcome may lead to novel treatment of combat wound infections in the future.

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