Document Type

Thesis

Degree

M.S.

Degree Granting Department

Biology (Cell Biology, Microbiology, Molecular Biology)

Major Professor

James Riordan

Co-Major Professor

Jill Roberts

Keywords

epidemiology, Escherichia coli, MLST, phylogeny, RAPD

Abstract

E. coli is the most frequently isolated Gram negative pathogen from bacteremia in cancer patients and is repeatedly recovered from many other extraintestinal illnesses. These infections are commonly endogenous in nature and interfere with the treatment of cancer resulting in increased healthcare costs, morbidity, and mortality rates. Cancer and the treatments related to cancer cause alterations in the microbiome of the gut and other organs. Despite this point, there is a serious lack of knowledge about the genetic types of E. coli infecting cancer patients. This gap results in vague prevention strategies and limited treatment options for cancer patients. Multi Locus Sequence Typing (MLST) was used to successfully genotype 105 sequentially collected E. coli isolates from patients admitted to H. Lee Moffitt Cancer Center (HLMCC, Tampa, FL) with confirmed extraintestinal infections between 2010 and 2012. In total, 24 distinct genotypes (STs) have been identified in this dataset using EcMLST (STEC Reference Center). Of these, ST34 constituted 39% of the isolates and may represent a disseminating clone at HLMCC. Furthermore, 17 isolates not found in the EcMLST database have been identified. Importantly, phylogenetic analysis of DNA sequence data for MLMCC E. coli revealed only 22% of HLMCC E. coli clustered with ECOR reference strains commonly attributed to the B2 phylogroup of extraintestinal pathogenic E. coli (ExPEC). Four HLMCC E. coli belonging to ST171 and attributed to life-threatening blood infections clustered with Shiga toxin (Stx) producing E. coli (STEC) strain TW06296. HLMCC E. coli belonging to ST34 clustered with enteroaggregative E. coli (EAEC) strain TW10263. Importantly, these non-B2 phylogroup strains demonstrated more pathogenic potential than HLMCC E. coli clustered with B2 ExPEC,which included a higher incidence of bacteremia and sepsis, as well as resistance to first-line antibiotics. Upon further investigation, ST34 may equate to ST131 by another MLST database. These findings suggest that isolates previously characterized as commensal and intestinal pathogenic E. coli have an increased ability to cause infection outside of the gastrointestinal tract in cancer patients and that selective pressures are contributing to increased antibiotic resistance. These findings may change the approach to clinical management of E. coli infections at cancer centers.

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