title: Network Analysis Reveals Sex- and Antibiotic Resistance-Associated Antivirulence Targets in Clinical Uropathogens.
abstract: Increasing antibiotic resistance among uropathogenicEscherichia 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.
authors.affiliation: Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States.
authors.forename: Kaveri S
authors.initials: KS
authors.lastname: Parker
authors.affiliation: Department of Statistics and Operations Research and Carolina Center for Interdisciplinary Applied Mathematics, Department of Mathematics, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Wilson
authors.affiliation: Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Department of Infectious Diseases, Bern University Hospital and University of Bern, 3010 Bern, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Marschall
authors.affiliation: Department of Statistics and Operations Research and Carolina Center for Interdisciplinary Applied Mathematics, Department of Mathematics, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mucha
authors.affiliation: Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States ; Center for Women's Infectious Diseases Research, Division of Infectious Diseases, and Department of Internal Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Henderson
keywords: UPEC; UTI; antibiotic resistance; network analysis; novel therapeutic targets; sex specificity in infections; uropathogens