Research Interests Bacterial urinary tract infection (UTI) is a major global public health problem and uropathogenic Escherichia coli (UPEC) is the predominant causative agent of UTI. Annual estimates for the incidence of UTI are ~11 million and ~150 million in the United States and around the world, respectively. High incidence of UTI and an alarming increase in antibiotic resistant uropathogens underscore the immediate need for development of novel strategies to mitigate UTI. We study the fitness and virulence mechanisms involved in the pathogenesis of bacterial UTI to identify novel targets that could be harnessed to develop therapeutics or prevention strategies against this ubiquitous infectious condition. We use a combination of bacteriological, biochemical, genetic, and functional genomic approaches, in conjunction with a mouse model, and ex vivo and in vitromodels to study key aspects of host-uropathogen interaction during UTI. Ongoing projects in the laboratory include elucidating the role of copper in UPEC survival and virulence during UTI, identification of small molecule inhibitors of UPEC virulence, developing a bladder organoid model to study the molecular pathogenesis of UTI in vitro, and investigating the biology of gut colonization by UPEC.
PEER-REVIEWED PUBLICATIONS Subashchandrabose S, Smith SN, DeOrnellas V, Crepin S, Zahdeh C, Kole MM, Mobley HL. 2015. Acinetobacter baumannii Genes Required for Bacterial Survival During Bloodstream Infection. mSphere 00013-15R1. In Press. Subashchandrabose S and Mobley HL. 2015. Back to the Metal Age: Battle for Metals at the Host-Pathogen Interface During Urinary Tract Infection.Metallomics. doi: 10.1039/C4MT00329B (Review). Brumbaugh AR, Smith SN, Subashchandrabose S, Himpsl SD, Hazen TH, Rasko DA, Mobley HL. 2015. Blocking Yersiniabactin Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and is a Novel Target to Prevent Urinary Tract Infection. Infect. Immun. doi: 10.1128/IAI.02904-14 Subashchandrabose S and Mobley HL. 2015. Virulence and Fitness Determinants of Uropathogenic E. coli. Microbiology Spectrum. doi: 10.1128/microbiolspec.UTI-0015-2012 (Review). *Subashchandrabose S, Hazen TH, Brumbaugh AR, Himpsl SD, Smith SN, Ernst RD, Rasko DA, Mobley HL. 2014. Host-specific Induction of Escherichia coli Fitness Genes During Human Urinary Tract Infection. Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1415959112. *Highlighted in Nat. Rev. Urology. doi:10.1038/nrurol.2014.366. Subashchandrabose S, Smith SN, Spurbeck RR, Kole MM, Mobley HL. 2013. Genome-wide Detection of Fitness Genes in Uropathogenic Escherichia coli During Systemic Infection. PLoS Pathog. doi: 10.1371/journal.ppat.1003788. Subashchandrabose S, Hazen TH, Rasko DA, Mobley HL. 2013. Draft Genome Sequences of Five Recent Human Uropathogenic Escherichia coliIsolates.Pathog. Dis. doi: 10.1111/2049-632X.12059. Subashchandrabose S, Leveque RM, Kirkwood RN, Kiupel M, Mulks MH. 2013. The RNA Chaperone Hfq Promotes Fitness of Actinobacillus pleuropneumoniaeDuring Porcine Pleuropneumonia. Infect. Immun. doi: 10.1128/IAI.00392-13. Subashchandrabose S, Leveque RM, Kirkwood RN, Kiupel M, Mulks MH. 2009. Branched-chain Amino Acids are Required for the Survival and Virulence ofActinobacillus pleuropneumoniae in Swine. Infect. Immun. doi: 10.1128/IAI.00671-09.