U.S. Army Medical Research Institute of Infectious Diseases, US Army Medical Research Insti Infec Diseases
We are interested in mechanisms of microbial pathogenesis with Yersinia pestis, Francisella tularensis, Bacillus anthracis, and the pathogenic Burkholderia spp (B. pseudomallei and B. mallei). The overall goal is to identify bacterial targets that these bacteria possess to identify novel vaccines or therapeutics. Ideally, a target for vaccination or a therapeutic would be necessary for virulence to avoid the natural selection or intentional manipulation of a resistant pathogen. Therefore, many of our laboratory projects involve the genetic construction of mutant strains in a gene encoding for the targeted protein. Virulence of the mutant strain is then assessed and compared to the parent strain through various in vitro and in vivo models of infection.
Additional studies in our laboratory focus on analyzing and characterizing mechanisms by which bacteria become resistant to antimicrobial compounds. By better understanding these mechanisms, approaches could be taken to identify methods to combat this problem.
References
Biot FV, Bachert BA, Mlynek KD, Toothman RG, Koroleva GI, Lovett SP, Klimko CP, Palacios GF, Cote CK, Ladner JT, Bozue JA. Evolution of Antibiotic Resistance in Surrogates of Francisella tularensis (LVS and Francisella novicida): Effects on Biofilm Formation and Fitness. Front Microbiol. 2020 Oct 30;11:593542. doi: 10.3389/fmicb.2020.593542.
Kijek TM, Mou S, Bachert BA, Kuehl KA, Williams JA, Daye SP, Worsham PL, Bozue JA. The D-alanyl-d-alanine carboxypeptidase enzyme is essential for virulence in the Schu S4 strain of Francisella tularensis and a dacD mutant is able to provide protection against a pneumonic challenge. Microb Pathog. 2019 Dec;137:103742.
Bachert BA, Biryukov SS, Chua J, Rodriguez SA, Toothman RG Jr, Cote CK, Klimko CP, Hunter M, Shoe JL, Williams JA, Kuehl KA, Biot FV, Bozue JA. A Francisella novicida Mutant, Lacking the Soluble Lytic Transglycosylase Slt, Exhibits Defects in Both Growth and Virulence. Front Microbiol. 2019 Jun 14;10:1343.
Chance T, Chua J, Toothman RG, Ladner JT, Nuss JE, Raymond JL, Biot FV, Demons S, Miller L, Halasohoris S, Mou S, Koroleva G, Lovett S, Palacios G, Vietri NJ, Worsham PL, Cote CK, Kijek TM, Bozue JA. A spontaneous mutation in kdsD, a biosynthesis gene for 3 Deoxy-D-manno-Octulosonic Acid, occurred in a ciprofloxacin resistant strain of Francisella tularensis and caused a high level of attenuation in murine models of tularemia. PLoS One. 2017 Mar 22;12(3):e0174106.
Bozue JA, Chaudhury S, Amemiya K, Chua J, Cote CK, Toothman RG, Dankmeyer JL, Klimko CP, Wilhelmsen CL, Raymond JW, Zavaljevski N, Reifman J, Wallqvist A. Phenotypic Characterization of a Novel Virulence-Factor Deletion Strain of Burkholderia mallei That Provides Partial Protection against Inhalational Glanders in Mice. Front Cell Infect Microbiol. 2016 Feb 26;6:21.
Bozue J, Cote CK, Chance T, Kugelman J, Kern SJ, Kijek TK, Jenkins A, Mou S, Moody K, Fritz D, Robinson CG, Bell T, Worsham P. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge. PLoS One. 2014 Aug 7;9(8):e104524.
Yersinia pestis; Francisella tularensis; Plague; Tularemia; Animal models; Burkholderia; Molecular biology; Infectious diseases; Bacterial pathogenesis;