Kristich Laboratory
Location
Microbiology & Immunology
TBRC C3653
General Interests
Antibiotic Resistance, Bacterial Genetics and Physiology, Bacterial Signal Transduction, Intestinal Colonization
Research Areas
We use a combination of genetics, biochemistry, genomics, molecular biology, and structural biology to study several interrelated problems in antibiotic-resistant bacteria. We primarily focus on enterococci, which are bacteria that both inhabit the intestinal tract and cause untreatable, antibiotic-resistant infections.
Genetic and biochemical basis for antibiotic resistance. We seek to define the molecular and cellular mechanisms by which enterococci overcome antibiotic treatment. In doing so, we will identify new targets for antibacterial molecules that disable antibiotic resistance, thereby providing an opportunity to restore the effectiveness of our existing antibiotics against untreatable infections.
Bacterial signal transduction. We are exploring the mechanisms by which enterococci sense changes in their environment and mount adaptive biological responses, including transmembrane Ser/Thr kinases and two-component signaling systems. We define signaling pathway components, signaling networks, conformational changes in signaling proteins, post-translational modifications that impact signal transduction, and effector outputs.
Bacterial cell wall synthesis. The enterococcal cell wall is essential for bacterial survival. We are defining mechanisms and regulation of cell wall synthesis, with the long-term goal of identifying weak points that can serve as targets for new antibiotics to treat antibiotic-resistant enterococcal infections.
Intestinal colonization. We are exploring the dynamics and molecular mechanisms of intestinal colonization by enterococci. We study how enterococci establish a foothold in the competitive intestinal environment, and how enterococcal populations in the intestine change in response to antibiotics and other environmental perturbations.
Current Members
Recent Publications
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(Mascari CA, Little JL, Kristich CJ.) Mol Microbiol. 2023 Dec;120(6):811-829 PMID: 37688380 PMCID: PMC10872757 SCOPUS ID: 2-s2.0-85170564562 09/09/2023
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(VanZeeland NE, Schultz KM, Klug CS, Kristich CJ.) J Mol Biol. 2023 Sep 15;435(18):168216 PMID: 37517789 PMCID: PMC10528945 SCOPUS ID: 2-s2.0-85166951228 07/31/2023
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Conformational changes in the activation loop of a bacterial PASTA kinase.
(Bluma MS, Schultz KM, Kristich CJ, Klug CS.) Protein Sci. 2023 Jul;32(7):e4697 PMID: 37312631 PMCID: PMC10303680 SCOPUS ID: 2-s2.0-85163810164 06/14/2023
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GpsB Promotes PASTA Kinase Signaling and Cephalosporin Resistance in Enterococcus faecalis.
(Minton NE, Djorić D, Little J, Kristich CJ.) J Bacteriol. 2022 Oct 18;204(10):e0030422 PMID: 36094306 PMCID: PMC9578390 SCOPUS ID: 2-s2.0-85140274238 09/13/2022
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CroR Regulates Expression of pbp4(5) to Promote Cephalosporin Resistance in Enterococcus faecalis.
(Timmler SB, Kellogg SL, Atkinson SN, Little JL, Djorić D, Kristich CJ.) mBio. 2022 Aug 30;13(4):e0111922 PMID: 35913163 PMCID: PMC9426447 SCOPUS ID: 2-s2.0-85137010276 08/02/2022
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(Mascari CA, Djorić D, Little JL, Kristich CJ.) J Bacteriol. 2022 Apr 19;204(4):e0060221 PMID: 35258319 PMCID: PMC9017299 SCOPUS ID: 2-s2.0-85128609674 03/09/2022
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IreK-Mediated, Cell Wall-Protective Phosphorylation in Enterococcus faecalis.
(Iannetta AA, Minton NE, Uitenbroek AA, Little JL, Stanton CR, Kristich CJ, Hicks LM.) J Proteome Res. 2021 Nov 05;20(11):5131-5144 PMID: 34672600 PMCID: PMC10037947 SCOPUS ID: 2-s2.0-85118785739 10/22/2021
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The enterococcal PASTA kinase: A sentinel for cell envelope stress.
(Djorić D, Minton NE, Kristich CJ.) Mol Oral Microbiol. 2021 Apr;36(2):132-144 PMID: 32945615 PMCID: PMC7969467 SCOPUS ID: 2-s2.0-85092077534 09/19/2020
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(Djorić D, Little JL, Kristich CJ.) Antimicrob Agents Chemother. 2020 Mar 24;64(4) PMID: 32041714 PMCID: PMC7179317 SCOPUS ID: 2-s2.0-85082388512 02/12/2020
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Reciprocal Regulation of PASTA Kinase Signaling by Differential Modification.
(Labbe BD, Hall CL, Kellogg SL, Chen Y, Koehn O, Pickrum AM, Mirza SP, Kristich CJ.) J Bacteriol. 2019 May 15;201(10) PMID: 30858297 PMCID: PMC6482931 SCOPUS ID: 2-s2.0-85065131964 03/13/2019
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Sortase-Dependent Proteins Promote Gastrointestinal Colonization by Enterococci.
(Banla LI, Pickrum AM, Hayward M, Kristich CJ, Salzman NH.) Infect Immun. 2019 Mar;87(5) PMID: 30804098 PMCID: PMC6479037 SCOPUS ID: 2-s2.0-85065021405 02/26/2019
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Colonization of the mammalian intestinal tract by enterococci.
(Banla LI, Salzman NH, Kristich CJ.) Curr Opin Microbiol. 2019 Feb;47:26-31 PMID: 30439685 PMCID: PMC6511500 SCOPUS ID: 2-s2.0-85056238106 11/16/2018