Dr Helen O Hare

I joined the University of Leicester in 2008 firstly as a Research Fellow and later as a Lecturer in microbiology. Previously I worked as a research fellow at the Swiss Federal Institute of Technology developing methods to detect protein-protein interaction to understand M. tuberculosis drug targets and as a post doctoral researcher at the University of Cambridge using directed evolution approaches to study enzyme specificity in antibiotic biosynthesis.

I am interested in bacterial physiology at the molecular level with a particular focus on human pathogens like Mycobacterium tuberculosis and on industrial strains. Recent achievements of my group include discovering a protein kinase signalling pathway that allows M. tuberculosis to regulate central metabolism by sensing amino acids in its surroundings.

Molecular mechanisms of sensory perception and metabolic regulation in bacteria

The main aim of my research group is to determine the molecular mechanisms by which bacteria sense and respond to their environment, with a particular focus on protein kinase G in the human pathogen Mycobacterium tuberculosis.

Phosphorylation at serine and threonine emerged as a ubiquitous mechanism of signal transduction in bacteria from genome sequencing in the 1990s. Serine and threonine protein kinases are now known to regulate critical bacterial processes including central carbon metabolism and cell division, but identification of the stimuli of kinase activation and the downstream effects of kinase activation are outstanding questions in the field.

My group study the complete PknG signalling pathway, from activation by amino acids to the downstream roles of kinase substrates in regulating central metabolism, with the result that PknG is one of only a handful of bacterial S/T kinases for which the activation stimuli are known, and arguably the only bacterial FHA-mediated signalling pathway with a complete molecular description (FHA=forkhead associated domain, a ubiquitous phospho-threonine recognition domain).

We are also working on the conserved pathways in the industrial “workhorse” Corynebacterium glutamicum (used to produce >$6 billion dollars of amino acids per year) and the antibiotic producing Streptomyces (>$1billion dollar market).

We collaborate with groups within the institute and Departments of Respiratory Science and Molecular and Cell Biology to validate anti-TB drug targets and for structure based drug discovery (Russell Wallis), to study protein phosphorylation at the level of the phosphoproteome and in regulation of bacterial cell growth (Galina Mukamolova), and to study the function of these signalling pathways in infection models (Leicester TB Research Group).

(0) A Virulence Associated Siderophore Importer Reduces Antimicrobial Susceptibility of Klebsiella pneumoniae
Robeena Farzand, Kumar Rajakumar, Michael R. Barer, Primrose P. E. Freestone, Galina V. Mukamolova, Marco R. Oggioni, Helen M. O'Hare
Front Microbiol. 2021; 12: 607512. 

Alqaseer K, Turapov O, Barthe P, Jagatia H, De Visch A, Roumestand C, Wegrzyn M, Bartek IL, Voskuill M I, O'Hare HM, Ajuh P, Bottrill AR, Witney AA, Cohen-Gonsaud M, Waddell SJ, Mukamolova GV (2019) Protein kinase B controls Mycobacterium tuberculosis growth via phosphorylation of the transcriptional regulator Lsr2 at threonine 112. Molecular Microbiology doi: 10.1111/mmi.14398

Farzand R, Rajakumar, K, Zumudio R, Oggioni MR, Barer MR, O'Hare HM (2019) ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae co-occurring and interacting with ICEKp1. Scientific Reports 9:13892 

Bhattacharyya N, Nkumama IN, Newland-Smith Z, Lin LY, Yin W, Cullen RE, Griffiths JS, Jarvis AR, Price MJ, Chong PY, Wallis R, O'Hare HM (2018) An aspartate-specific solute-binding protein regulates protein kinase G activity to control glutamate metabolism in Mycobacteria. mBio 9(4): mBio00931-18.

Rieck B, Degiacomi G, Zimmermann M, Cascioferro A, Boldrin F, Lazar-Adler NR, Bottrill AR, le Chevalier F, Frigui W, Bellinzoni M, Lisa MN, Alzari PM, Nguyen L, Brosch R, Sauer U, Manganelli R, O'Hare HM (2017) PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis. PLoS Pathog 13(5): e1006399

Ventura M, Rieck B, Boldrin F, Degiacomi G, Bellinzoni M, Barilone N, Alzaidi F, Alzari PM, Manganelli R, O'Hare HM (2013) GarA is an essential regulator of metabolism in Mycobacterium tuberculosis. Mol Microbiol. 90(2):356-66. 

Bortoluzzi A, Muskett FW, Waters LC, Addis, PW, Rieck B, Munder R, Schleier S, Forti F, Ghisotti D, Carr MD, O'Hare HM (2013) Structural characterization of Mycobacterium tuberculosis RNA polymerase binding protein A (RbpA) and its interactions with sigma factors. Journal of Biological Chemistry 288 (20) 14438-50.

O'Hare HM, Duran R, Cervenansky C, Bellinzoni M, Wehenkel A, Pritsch O, Obal G, Baumgartner J, Vialaret J, Johnsson K, Alzari PM (2008) Regulation of glutamate metabolism by protein kinase G in mycobacteria. Mol Microbiol. 70 (6) 1408-1423.

Sacco E, Suarez A, O'Hare HM, Carroll P, Eynard N, Jones TA, Parish T, Daffe M, Backbro K, Quemard A (2007) The missing piece of the type II Fatty Acid Synthase system from Mycobacterium tuberculosis. PNAS. 104, 14628-14633.

• Bacterial sensory perception and signalling
• Mycobacterium tuberculosis
• Bacterial metabolism: central metabolism or secondary metabolism including antibiotic biosynthesis
• Structure-function relationships of bacterial proteins

I am the programme director for BSc Medical Microbiology and BSc Biological Sciences (microbiology) and associated MBiol courses.

I teach on modules in years 1-3 of Biological Sciences such as BS1040 The Cell MB2020 Medical Microbiology MB3020 Advanced topics in medical microbiology.