@article{cfe77a73fb3049c4b89093075598b3cd,
title = "Network Analysis Reveals Sex- and Antibiotic Resistance-Associated Antivirulence Targets in Clinical Uropathogens",
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",
author = "Parker, {Kaveri S.} and Wilson, {James D.} and Jonas Marschall and Mucha, {Peter J.} and Henderson, {Jeffrey P.}",
note = "Funding Information: We thank B. Foxman and L. Zhang (University of Michigan, Ann Arbor, MI, USA) for dot-blot hybridization analysis. We also thank C. A. Burnham, E. Casabar, and the Barnes-Jewish Hospital Microbiology Laboratory for assistance with clinical isolates and antibiotic resistance records. J.P.H. holds a Career Award for Medical Scientists from the Burroughs-Wellcome Fund and acknowledges NIH Grants R01DK099534 and P50DK064540. J.M. acknowledges NIH Grants UL1RR024992, KL2RR024994, and BIRCWH 5K12HD001459-13. J.D.W. acknowledges NSF Grant DMS-1310002. P.J.M. acknowledges support from the James S. McDonnell Foundation 21st Century Science Initiative − Complex Systems Scholar Award Grant 220020315. J.P.H. and K.S.C. additionally acknowledge the Longer Life Foundation and the Center for Women{\textquoteright}s Infectious Disease Pilot Research Project Grant. Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",
year = "2016",
month = jan,
day = "8",
doi = "10.1021/acsinfecdis.5b00022",
language = "English",
volume = "1",
pages = "523--532",
journal = "ACS Infectious Diseases",
issn = "2373-8227",
number = "11",
}