His research focused on the mechanism by which Gram-negative bacilli colonize the human host, elude the innate immune response, and disseminate from primary sites of infection including the urinary tract into the bloodstream.
In 2004, he moved the laboratory to the University of Michigan Medical School to continue this work and to serve as Chair of the Department of Microbiology and Immunology until 2019.
), 38 postdoctoral fellows, and 5 research track faculty, his lab advanced the field's understanding of the molecular pathogenesis of E. coli and P. mirabilis UTIs, the gastric pathogen Helicobacter pylori, and other Gram-negative species.
He conducted postdoctoral work at the University of Maryland School of Medicine in Biochemistry and Vaccine Development after which he joined the faculty in the Division of Infectious Diseases in 1984.
Departmental Administration Harry LT Mobley, PhD, was recruited to the University of Michigan as the Frederick G Novy Collegiate Professor & Chair of the Department of Microbiology & Immunology in 2004.
They identified 13 pathogenicity islands inserted into the genome and characterized virulence determinants including P and type 1 fimbriae, flagella, hemolysin (other toxins), and multiple iron acquisition systems.
In addition, using a pathogen-specific microarray, they measured expression levels for all genes from E. coli CFT073 collected directly from the urine of experimentally infected mice and women with cystitis.
They extended these studies by measuring global gene expression in E. coli strains in the urine of women during active UTIs using RNA-Seq technologies.
Forsyth, Valerie S., Chelsie E. Armbruster, Sara N. Smith, Ali Pirani, A. Cody Springman, Matthew S. Walters, Greta R. Nielubowicz, Stephie D. Himpsl, Evan S. Snitkin, and Harry L.T.
Sintsova, Anna, Arwen Frick-Cheng, Sara Smith, Ali Pirani, Sargurunathan Subashchandrabose, Evan S. Snitkin, and Harry L.T.
Subashchandrabose, Sargurunathan, Tracy H. Hazen, Ariel R. Brumbaugh, Stephanie D. Himpsl, Sara N. Smith, Robert D. Ernst, David A. Rasko, and Harry L.T.
Gene expression profile of uropathogenic Escherichia coli in women with uncomplicated urinary tract infection is recapitulated in the mouse model.
The environment within the bladder either selects or signals production of MR/P fimbriae, as >85% of the bacteria are expressing this surface structure two to four days after infection, as detected by the orientation of the mrp promoter that resides on an invertible element.
These virulence proteins include urease, flagellin, autotransported proteases, hemolysin, MR/P (and numerous other) fimbriae, the type VI secretion system, and a number of metabolic enzymes.
The Mobley lab had a longstanding interest in the development of vaccines to protect humans against urinary tract infections by uropathogenic bacterial species including both E. coli and Proteus mirabilis.
Forsyth, Valerie S., Stephanie D. Himpsl, Sara N. Smith, Christina A. Sarkissian, Laura A. Mike, Jolie A. Stocki, Anna Sintsova, Christopher J. Alteri, and Harry L.T.
Siderophore vaccine conjugates protect against uropathogenic Escherichia coli urinary tract infection Proceedings of the National Academy of Sciences, USA.
Bacteremia has three phases of pathogenesis: initial primary site infection, dissemination to the bloodstream, and growth and survival in blood and blood-filtering organs (PMID33692149).
Whereas current antibiotics are based on the ability to kill or inhibit bacterial growth in vitro, there is an opportunity to identify drug targets that are specifically required during infection.
Although phenotypically similar in terms of antimicrobial resistance and biochemical identification tests, these Gram-negative species nevertheless represent a heterogeneous group of strains that differs in virulence mechanisms, primary sites of infection, and metabolic pathways.
The Mobley and Bachman Labs addressed the relative lack of rigorous studies of the pathogenesis and potential for novel treatments of Enterobacterales bacteremia.
Holmes CL, Smith SN, Gurczynski SJ, Severin GB, Unverdorben LV, Vornhagen J, Mobley HLT, Bachman MA.
Anderson MT, Brown AN, Pirani A, Smith SN, Photenhauer AL, Sun Y, Snitkin ES, Bachman MA, Mobley HLT.
The UDP-GalNAcA biosynthesis genes gna-gne2 are required to maintain cell envelope integrity and in vivo fitness in multi-drug resistant Acinetobacter baumannii.
Armbruster CE, Forsyth VS, Johnson AO, Smith SN, White AN, Brauer AL, Learman BS, Zhao L, Wu W, Anderson MT, Bachman MA, Mobley HLT.
Holmes, Caitlyn L., Alexis E. Wilcox, Valerie Forsyth, Sara N. Smith, Bridget S. Moricz, Lavinia V. Unverdorben, Sophia Mason, Lili Zhao, Harry L.T.
Helicobacter pylori, a gram-negative, microaerophilic, spiral-shaped bacterium is the most frequently cited etiologic agent of human gastritis and peptic ulceration.
This species, whose niche is highly restricted to the gastric mucosa of humans, has adopted a strategy of survival that includes synthesis of urease as its most abundant cellular protein.
An additional gene necessary for production of highly active urease was discovered and encoded a single component nickel transport system.
Mobley, Bianca Brahamsha, James Brown, Larry Forney, Robert Haselkorn, Jennie Hunter-Cevera, Stanley Maloy, Beth McCormick, Carlos Pedros Alio (eds.).