Characterization of A. baumannii Environmental Survival and Biofilm Formation and the Impact on Environmental Transmission.

Abstract

Acinetobacter baumannii is a gram-negative, opportunistic pathogen primarily affecting the critically ill, causing 3% of all nosocomial-related deaths in the United States. A. baumannii’s successful environmental survival within the hospital environment is attributed to its ability to form biofilms, tolerate desiccation and be multidrug resistant (MDR). Understanding the relationship between these virulence factors will help minimize environmental-mediated transmissions of A. baumannii. To characterize fitness trade-offs imposed on A. baumannii by clinical and environmental settings, I compared rep-PCR banding patterns, antibiotic susceptibilities, biofilm formation and desiccation tolerance of 115 clinical and 54 environmental isolates collected from the University of Michigan Hospital. The MDR phenotype was deleterious for environmental-isolated strains (yet beneficial for patient-isolated strains) and biofilms were critical for environmental strain desiccation tolerance. This study improves our understanding of the association of the MDR phenotype with persistence, and demonstrates that the association is mediated by environmental conditions. Biofilms can disseminate contamination via detachment of sessile cells that are assumed characteristically planktonic. I investigated this assumption by comparing antibiotic susceptibilities of A. baumannii planktonic, biofilm, and detached sessile cells. Detached cells were phenotypically distinct with respect to antibiotic susceptibilities, suggesting that antibiotic therapies should target detached cells rather than planktonic cells for biofilm-related infections. A simplifying assumption in mathematical modeling is that the skin-surface exchange of contamination is symmetrical. My final study challenged this assumption by measuring the bi-directional transfer efficiencies of A. baumannii and evaluated the change in risk of pathogen transport between patients by comparing fate-and-transport mathematical models with contrasting symmetry assumptions. These studies demonstrated that the transfer efficiencies were asymmetrical and the assumption of symmetry minimized the true impact of healthcare worker-mediated transmission. This dissertation advances our understanding of the association between resistance, biofilms, and persistence. Results of my investigations will improve the accuracy of environmental-mediated infectious disease transmission system models and can be used to strengthen guidelines to control healthcare-associated infections. Further, the results provide new insights, that I hope will stimulate innovative approaches to reduce the risk of biofilm-related infections and curtail the environmental persistence and transmission of A. baumannii.