STUDIES ON THE ROLE OF A SMALL RNA IN T6SS DYNAMICS OF ACINETOBACTER BAUMANNII DURING OXIDATIVE STRESS

Abstract

The emergence of antibiotic-resistant microorganisms as a major threat to public healthcare systems is a growing concern. Acinetobacter baumannii, a Gram-negative bacteria, has become a leading source of nosocomial infections, and some isolates are even multidrug-resistant (MDR). A. baumannii causes wound and burn infections, sepsis, meningitis, urinary tract infections (UTIs), bloodstream, and ventilator-associated pneumonia. A. baumannii that is resistant to carbapenem (the last resort of antibiotics) is categorized as a top-priority critical pathogen by the World Health Organization (WHO). Since A. baumannii is often found in polymicrobial infections alongside other bacteria, A. baumannii likely tends to compete with other pathogens to survive in a hostile environment. It has been demonstrated that numerous Gram-negative bacteria use the type VI secretion system (T6SS) as a molecular arsenal to kill other bacteria by injecting toxic effector proteins and triggering contact-dependent death. T6SS-mediated contact-dependent killing was first observed in A. baumannii ATCC 17978 in 2013. Bacteria also use the T6SS to deliver effector molecules to influence host-mediated immune responses and colonize inside the host. During bacterial infection, the host recruits phagocytic cells such as neutrophils and macrophages, which sequester free metal ions (Mn2+, Zn2+, Fe2+/3+, etc.) at the infection site, termed “host-mediated nutritional immunity” and create oxidative stress. It has been reported that certain bacteria employ T6SS to sequester free metal ions from the extracellular milieu and help to cope with oxidative stress and host-mediated free metal limitation. However, such role of T6SS in A. baumannii’s ability to survive under phagocytic cell-mediated killing has not yet been explored. Mn2+ sequestration by neutrophils at the infection site suppresses bacterial superoxide dismutase (SOD) and catalase activity, which bacteria utilize to breakdown reactive oxygen species (ROS) produced by phagocytic cells. To acquire the Mn2+ required for survival, metabolism, and regulation of various virulence factors, A. baumannii utilizes a high-affinity Mn2+-acquisition system MumT against host-mediated free metal limitation during infection. Although Mn2+-uptake systems have been reported as one of the key virulence factors in pathogenic bacteria, the crosstalk of Mn2+-transporter and T6SS remains unknown in A. baumannii.