Network Analysis Reveals Sex- and Antibiotic Resistance-Associated Antivirulence Targets in Clinical Uropathogens

ACS Infect Dis. 2015 Nov 13;1(11):523-532. doi: 10.1021/acsinfecdis.5b00022. Epub 2015 Jul 24.

Abstract

Increasing antibiotic resistance among uropathogenic Escherichia coli (UPEC) is driving interest in therapeutic targeting of nonconserved virulence factor (VF) genes. The ability to formulate efficacious combinations of antivirulence agents requires an improved understanding of how UPEC deploy these genes. To identify clinically relevant VF combinations, we applied contemporary network analysis and biclustering algorithms to VF profiles from a large, previously characterized inpatient clinical cohort. These mathematical approaches identified four stereotypical VF combinations with distinctive relationships to antibiotic resistance and patient sex that are independent of traditional phylogenetic grouping. Targeting resistance- or sex-associated VFs based upon these contemporary mathematical approaches may facilitate individualized anti-infective therapies and identify synergistic VF combinations in bacterial pathogens.

Keywords: UPEC; UTI; antibiotic resistance; network analysis; novel therapeutic targets; sex specificity in infections; uropathogens.