Healthcare-associated infections (HAIs) are a significant cause of morbidity and mortality in the United States and cost up to $4.5 billion annually. Horizontal gene transfer (HGT) contributes to the evolution and emergence of pathogenic strains causing these infections by allowing DNA to be shared among diverse bacteria. This dissertation identifies and investigates the molecular mechanisms that affect HGT between bacteria and the factors that govern HGT at the patient level.

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.