Dr Sharon Kendall
Department: Pathobiology and Population Sciences
Research Groups: Antimicrobial Resistance, Host-Pathogen Interactions and Vaccinology, IRLFS (Research Programme)
I am a Senior Lecturer in Molecular Bacteriology and a member of the Livestock Production and Population health research programme. My research expertise is in tuberculosis (TB) caused by bacteria of the M. tuberculosis complex (MTBC. I am trying to understand how members of the MTBC adapts in order to survive within the host for extended periods of time and the genetic basis of survival within the host.
I completed a BSc in Genetics at the University of Swansea and a PhD in antibiotic resistance in E. coli at the University of Bristol. My PhD studies looked at the phenomenon of antibiotic tolerance - a process whereby bacterial growth is inhibited by the presence of the antibiotics but survival and regrowth is observed on removal. I began to start work as a Post-Doctoral Fellow with Mycobacterium tuberculosis in 2000 first at the London School of Hygiene and Tropical Medicine and subsequently at The Royal Veterinary College. I was appointed as a Lecturer in Microbiology in 2007 and as Senior Lecturer in 2017.
I am interested in the genetic basis of virulence in members of the MTBC, causative agents of TB in both humans and animals. I am PI of a BBSRC funded project entitled "Mycobacterial determinants of survival and fitness within the bovine host" and the aim of this project is to define those genes that are essential for the survival of M. bovis, the causative agent of bovine TB, in cellular and in in vivo models. We hope that the information generated in this project will be able to inform novel vaccine design for both human and cattle TB. I am also interested in the genetic basis of host preference in members of the MTBC and the functional consequences of the large scale and single nucleotide polymorphisms that exist between different members. Additionally, as a molecular microbiologist I am interested in developing new molecular tools for manipulating mycobacteria and we are currently trying to develop CRISPR based tools for gene editing and interference.
- Gibson AJ, Passmore IJ, Faulkner V, Xia D, Nobeli I, Stiens J, Willcocks S, Clark TG, Sobowiak B, Werling D, Villarreal-Ramos B, Wren BW and Kendall SL (2021). Probing Differences in Gene Essentiality Between the Human and Animal Adapted Lineages of the Mycobacterium tuberculosis Complex Using TnSeq. Frontiers in Veterinary Science 8:760717. https://doi.org/10.3389/fvets.2021.760717
- Schuller M, Butler RE, Ariza A, Tromans-Coia C, Jankevicius G, Claridge TDW, Kendall SL, Goh S, Stewart GR, Ahel I. Molecular basis for DarT ADP-ribosylation of a DNA base. Nature (2021) 596: doi:10.1038/S41586-021-03825-4
- Faulkner V, Cox AA, Goh S, van Bohemen A, Gibson AJ, Liebster O, Wren BW, Willcocks S, Kendall SL. 2020. Re-sensitization of Mycobacterium smegmatis to Rifampicin Using CRISPR Interference Demonstrates Its Utility for the Study of Non-essential Drug Resistance Traits. Frontiers in Microbiology 11:619427
- Perrone F, De Siena B, Muscariello L, Kendall SL, Waddell SJ, Sacco M: A Novel TetR-like transcriptional regulator is induced in acid-nitrosative stress and controls expression of an efflux pump in mycobacteria. Frontiers in Microbiology 2017, 8:2039.
- Kamaruzzaman NF, Kendall S, and Good L: Targeting the hard to reach: challenges and novel strategies in the treatment of intracellular bacterial infections. British Journal of Pharmacology 2016, 174(14): 2225-2236
- Ho NA, Dawes SS, Crowe AM, Casabon IE, Gao C, Kendall SL, Baker EN, Eltis LD, Lott JS: The structure of the transcriptional repressor Kstr in complex with CoA thioester cholesterol metabolites sheds light on the regulation of cholesterol catabolism in Mycobacterium tuberculosis. The Journal of biological chemistry 2016, 291:7256-7266.
- Mbugi EV, Katale BZ, Siame KK, Keyyu JD, Kendall SL, Dockrell HM, Streicher EM, Michel AL, Rweyemamu MM, Warren RM et al: Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania. Tuberculosis 2015, 95(2):170-178.
- Balhana RJ, Singla A, Sikder MH, Withers M, Kendall SL: Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions. BMC genomics 2015, 16:479.
- Katale BZ, Mbugi EV, Botha L, Keyyu JD, Kendall S, Dockrell HM, Michel AL, Kazwala RR, Rweyemamu MM, van Helden P et al: Species diversity of non-tuberculous mycobacteria isolated from humans, livestock and wildlife in the Serengeti ecosystem, Tanzania. BMC Infect Dis 2014, 14(1):616.
- Evangelopoulos D, Gupta A, Lack NA, Maitra A, ten Bokum AM, Kendall S, Sim E, Bhakta S: Characterisation of a putative AraC transcriptional regulator from Mycobacterium smegmatis. Tuberculosis 2014, 94(6):664-671.
- Dawes SS, Kendall SL, Baker EN, Lott JS: Purification, crystallization and preliminary X-ray crystallographic studies of KstR2 (ketosteroid regulatory protein) from Mycobacterium tuberculosis. Acta Crystallographica Section F-Structural Biology Communications 2014, 70:1643-1645.
- Katale BZ, Mbugi EV, Karimuribo ED, Keyyu JD, Kendall S, Kibiki GS, Godfrey-Faussett P, Michel AL, Kazwala RR, van Helden P et al: Prevalence and risk factors for infection of bovine tuberculosis in indigenous cattle in the Serengeti ecosystem, Tanzania. BMC Vet Res 2013, 9:267.
- Balhana RJ, Swanston SN, Coade S, Withers M, Sikder MH, Stoker NG, Kendall SL: bkaR is a TetR-type repressor that controls an operon associated with branched-chain keto-acid metabolism in Mycobacteria. FEMS Microbiol Lett 2013, 345(2):132-140.
- Uhia I, Galan B, Kendall SL, Stoker NG, Garcia JL: Cholesterol metabolism in Mycobacterium smegmatis. Environmental Microbiology Reports 2012, 4(2):168-182.
- Mbugi EV, Kayunze KA, Katale BZ, Kendall S, Good L, Kibik GS, Keyyu JD, Godfrey-Faussett P, Van Helden P, Matee MI: 'One Health' infectious diseases surveillance in Tanzania: are we all on board the same flight? Onderstepoort J Vet Res 2012, 79(2):500.
- Mbugi EV, Katale BZ, Kendall S, Good L, Kibiki GS, Keyyu JD, Godfrey-Faussett P, Van Helden P, Matee MI: Tuberculosis cross-species transmission in Tanzania: towards a One-Health concept. Onderstepoort J Vet Res 2012, 79(2):501.
- Katale BZ, Mbugi EV, Kendall S, Fyumagwa RD, Kibiki GS, Godfrey-Faussett P, Keyyu JD, Van Helden P, Matee MI: Bovine tuberculosis at the human-livestock-wildlife interface: is it a public health problem in Tanzania? A review. Onderstepoort J Vet Res 2012, 79(2):463.
- Balhana R, Stoker NG, Sikder MH, Chauviac FX, Kendall SL: Rapid construction of mycobacterial mutagenesis vectors using ligation-independent cloning. J Microbiol Methods 2010, 83(1):34-41.
- Kendall SL, Frita R: Construction of targeted mycobacterial mutants by homologous recombination. Methods Mol Biol 2009, 465:297-310.
- Kendall SL, Burgess P, Balhana R, Withers M, Ten Bokum A, Lott JS, Gao C, Uhia-Castro I, Stoker NG: Cholesterol utilization in mycobacteria is controlled by two TetR-type transcriptional regulators: kstR and kstR2. Microbiology 2009, 156(5):1362-1371.
- Sharpe ML, Gao C, Kendall SL, Baker EN, Lott JS: The structure and unusual protein chemistry of hypoxic response protein 1, a latency antigen and highly expressed member of the DosR regulon in Mycobacterium tuberculosis. J Mol Biol 2008, 383(4):822-8
- Senaratne RH, Sidders B, Sequeira P, Saunders G, Dunphy K, Marjanovic O, Reader JR, Lima P, Chan S, Kendall S et al: Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice. J Med Microbiol 2008, 57(2):164-170.
- Sidders B, Withers M, Kendall SL, Bacon J, Waddell SJ, Hinds J, Golby P, Movahedzadeh F, Cox RA, Frita R et al: Quantification of global transcription patterns in prokaryotes using spotted microarrays. Genome Biol 2007, 8(12):265.
- Kendall SL, Withers M, Soffair CN, Moreland NJ, Gurcha S, Sidders B, Frita R, Ten Bokum A, Besra GS, Lott JS et al: A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis. Mol Microbiol 2007, 65(3):684-699.
- Campbell DR, Chapman KE, Waldron KJ, Tottey S, Kendall S, Cavallaro G, Andreini C, Hinds J, Stoker NG, Robinson NJ et al: Mycobacterial cells have dual nickel-cobalt sensors: sequence relationships and metal sites of metal-responsive repressors are not congruent. The Journal of biological chemistry 2007, 282(44):32298-32310.
- Bacon J, Dover LG, Hatch KA, Zhang Y, Gomes JM, Kendall S, Wernisch L, Stoker NG, Butcher PD, Besra GS et al: Lipid composition and transcriptional response of Mycobacterium tuberculosis grown under iron-limitation in continuous culture: identification of a novel wax ester. Microbiology 2007, 153(5):1435-1444.
I am currently module leader for the Infection and Immunity module, and deputy module leader for the Applied Molecular Microbiology Module, Principles in Infectious Diseases Module and Control of Infectious Diseases available on the BSc in Biological and BioVeterinary Science course (years 2 and 3). I am academic tutor for the BVetMed course in the pre-clinical years (year 1 and 2). I also teach on the BVetMed course, the BSc in Veterinary Nursing and the MSc in One Health. I frequently supervise undergradute students and postgraduate student research projects, including PhDs. I have also completed a Post Graduate Certificate in Veterinary Education and I am a Fellow of the Higher Education Academy (FHEA).
Myself and my laboratory members are keen to take to opportunities to participate in outreach. To date we have participated in the RVC Masterclass sessions, worked with Secondary school and Primary school students to help inspire an interest in Microbiology and have delivered a session for the family fun day at the Royal Society ("Spooky Science October 2017).
Development of rapid diagnostics to detect mycobacterial infections
Mycobacteria are very difficult to culture and can take weeks to grow. The aim of this project is to is to use novel patented bacteriophage technology to rapidly detect and diagnose infections caused by mycobacteria, such as Tuberculosis and Johne’s disease. Mycobacterial pathogens are responsible for a range of diseases in both humans and animals. TB in humans is primarily caused by M. tuberculosis and TB in cattle is primarily caused by M. bovis. Both organisms are members of the Mycobacterium tuberculosis complex group of organisms.
Functional genomics of the Mycobacterium tuberculosis complex
The Mycobacterium tuberculosis complex is comprised of a group of closely related bacteria with distinct host preferences. Species such as Mycobacterium bovis causes TB in animals, but has a wide host range. Species such as Mycobacterium tuberculosis and Mycobacterium africanum primarily cause TB in humans. Human TB is one of the top 10 causes of death from a single infectious agent and causes approximately 1.5 million deaths annually.