Contribution of Horizontal Gene Transfer to Virulence and Antibiotic Resistance to Pathogens Transmitted in Healthcare Facilities

Healthcare-associated infections (HAIs) are a significant cause of morbidity and mortality in the United States and cost up to ;Catheter-associated urinary tract infection (caUTI), the most common HAI, is often polymicrobial. Using comparative genomics, this study identified ICEPm1, a genomic island shared among Proteus mirabilis , Providencia stuartii, and Morganella morganii , common agents of polymicrobial caUTI. We show that this island is an integrative and conjugative element that is self-transmissible between clinical strains at a frequency of 1.35 x 10-5 and that transfer is dependent on an integrase and a type IV secretion system encoded within the element. ICEPm1 also encodes an adhesin and known iron-acquisition system; therefore ICEPm1 may provide a fitness advantage during colonization of the catheterized urinary tract. In support of this, I observed that ICEPm1 was present in 39/39 P. mirabilis urinary isolates screened, while distribution was heterogeneous (15/23) among P. mirabilis commensal strains.;Because proximity is necessary for HGT to occur, we investigated risk factors for co-colonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) among residents of long-term care facilities. Co-colonization with these organisms is of interest because of the emergence of vancomycin-resistant S. aureus (VRSA); attributable to HGT of the vanA gene cluster from VRE to MRSA. Because MRSA remains susceptible to vancomycin the emergence of vancomycin-resistant S. aureus is alarming for healthcare professionals. We show that wounds, indwelling devices and functional disability are risk factors for co-colonization with MRSA and VRE; an event that precedes VRSA emergence.;This dissertation provides insight into the mechanisms of transfer of mobile elements and therefore dissemination of virulence and antibiotic resistance genes. It also describes risk factors for co-colonization with MRSA and VRE within a patient, an event that is necessary for HGT to occur in vivo.