Revathi Govind, Associate Professor

Contact information

Revathi Govind

Education

Ph.D. 2006, Texas Tech University HSC. Microbiology and Immunology.

Area(s) of Specialization

Pathogenic Microbiology, Bacterial Genetics.

Research Focus

Principal research interest of our lab is to study the molecular mechanisms of Clostridioides difficile pathogenesis to develop more effective diagnostic tools and therapeutic agents. Given below are the two major projects that we are most excited about.

Regulatory Pathways that Link difficile Sporulation with Toxin Production: The two major virulence determinants of C. difficile pathogenesis are its ability to produce toxins and spores. TcdR is the sigma factor needed for the transcription of toxin genes. Our results with C. difficile tcdR mutants are exciting and suggest a close interplay between toxin gene regulation and sporulation in C. difficile. Additionally, we have identified and characterized new master regulators (SinR and SinI) in C. difficile that control multiple pathways, including toxin production, sporulation, motility, and biofilm formation (a, b). Follow-up work on the sin locus revealed that its regulation is under the control of Spo0A, the master regulator of sporulation (c). We are currently identifying genes directly regulated by SinR and SinI. While investigating two distinct colony morphologies in the UK1 C. difficile strain, we discovered that c-di-GMP controls sporulation in C. difficile (d). An R01 application on this investigation is currently pending. Our recent study on CodY variants in C. difficile revealed that mutations in specific regions of this nutrient-sensing master regulator influence its ligand-binding ability. I was awarded an R21 grant to investigate the role of these variants in C. difficile virulence.

a) PMID: 28217744; b) PMID: 29529083; c) PMID: 33148827; PMID: 34606654.
The Role of Complex Carbohydrates in C. difficile In Vivo Colonization and Pathogenesis: Dietary carbohydrates are known to modulate virulence in C. difficile. Our lab characterized the role of cellobiose in C. difficile virulence by identifying and characterizing the role of the cellobiose utilization operon and its regulator CelR (e). More recently, we have shown that glycogen produced during the stationary phase of C. difficile is stored in its spores, contributing to its resilience. These resilient spores with glycogen are necessary for C. difficile reinfection in the hamster model (f).

e) PMID: 34410904; f) Hasan MK, et al. 2024. PMID: 39189778.

We are excited to further explore this challenging and difficult pathogen, hoping to make new discoveries that could be leveraged to develop effective therapeutics against C. difficile

Selected Publications

Hasan MK, Alaribe O, Govind R. 2004. Regulatory networks: Linking toxin production and sporulation in Clostridioides difficile. Anaerobe. 2024 Nov 7;91:102920. doi: 10.1016/j.anaerobe.2024.102920. Epub ahead of print. PMID: 39521117.

Hasan MK, Pizzarro-Guajardo M, Sanchez J, Govind R. 2024. Role of glycogen metabolism in Clostridioides difficile virulence. mSphere. 2024 Sep 25;9(9):e0031024. doi: 10.1128/msphere.00310-24. Epub 2024 Aug 27. Erratum in: mSphere. 2024 Nov 21;9(11):e0083524. doi: 10.1128/msphere.00835-24. PMID: 39189778; PMCID: PMC11423593.

Dhungel BA, Govind R. 2021. Phase-variable expression of pdcB, a phosphodiesterase, influences sporulation in Clostridioides difficile . Mol Microbiol. 2021 Oct 4. doi: 10.1111/mmi.14828. PMID: 34606654.

Hasan MK, Dhungel BA, Govind R. 2021. Characterization of an operon required for growth on cellobiose in Clostridioides difficile . Microbiology 2021 Aug;167(8):001079. doi: 10.1099/mic.0.001079. PMID: 34410904.

Dhungel BA, Govind R. 2020. Spo0A Suppresses sin Locus Expression in Clostridioides difficile . mSphere. 2020 Nov 4;5(6):e00963-20. doi: 10.1128/mSphere.00963-20. PMID: 33148827; PMCID: PMC7643835.

Brungardt J, Govind R, Trick HN. 2020. A simplified method for producing laboratory grade recombinant TEV protease from E. coli. Protein Expr Purif. 2020 Oct;174:105662. doi: 10.1016/j.pep.2020.105662. Epub 2020 May 5. PMID: 32387144.

Ciftci Y, Girinathan BP, Dhungel BA, Hasan MK, Govind R. 2019. Clostridioides difficile SinR' regulates toxin, sporulation and motility through protein-protein interaction with SinR. Anaerobe. 2019 Oct;59:1-7. doi: 10.1016/j.anaerobe.2019.05.002. Epub 2019 May 8. PMID: 31077800; PMCID: PMC6785386.

Girinathan BP, Ou J, Dupuy B, Govind R. 2018. Pleiotropic roles of Clostridium difficile sin locus. PLoS Pathog 2018 Mar 12;14(3):e1006940. doi: 10.1371/journal.ppat.1006940. eCollection 2018 Mar.

Girinathan BP, Monot M, Boyle D, McAllister KN, Sorg JA, Dupuy B, Govind R. 2017. Effect of tcdR Mutation on Sporulation in the Epidemic Clostridium difficile Strain R20291. mSphere 2017 Feb 15;2(1). pii: e00383-16. doi: 10.1128/mSphere.00383-16. PMID:28217744.

Girinathan BP, Braun S, Sirigireddy AR, Espinola-Lopez J, Govind R. 2016. Importance of Glutamate Dehydrogenase (GDH) in Clostridium difficile Colonization In Vivo . PLoS One 2016 Oct 21;11(10):e0165579. doi: 10.1371/journal.pone.0165579.PMID:27768767.

Govind R, Fitzwater L, Nichols R. 2015. Observations on the Role of TcdE Isoforms in Clostridium difficile Toxin Secretion. J Bacteriol. 2015 Aug 1;197(15):2600-9. doi: 10.1128/JB.00224-15. Epub 2015 May 26. PMID: 26013487.

Girinathan PB, Braun S, Govind R. 2014. The Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to hydrogen peroxide. Microbiology. 2014 Jan;160(Pt 1):47-55. PMID: 24145018.

Sirigi Reddy AR, Girinathan PB, Zapotocny R, Govind R. 2013. Identification and Characterization of Clostridium sordellii Toxin Gene Regulator. J Bacteriol. 2013 Sep; 195(18): 4246-5. PMID: 23873908.

Collery M, Govind R, Minton P, Kuehne S. 2013. Pathogenicity Mechanisms of Clostridium difficile. Book Chapter. In Advances with Clostridium difficile. Editors. Karl Weiss & Dr Glenn Tillotson.

View the complete publication list in NCBI