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

Kaveri S. Parker, James D. Wilson, Jonas Marschall, Peter J. Mucha, Jeffrey P. Henderson

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)523-532
Number of pages10
JournalACS Infectious Diseases
Volume1
Issue number11
DOIs
StatePublished - Jan 8 2016

Keywords

  • UPEC
  • UTI
  • antibiotic resistance
  • network analysis
  • novel therapeutic targets
  • sex specificity in infections
  • uropathogens

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