The overarching goal of this research programme is focused on the development of novel treatment strategies to combat Mycobacterium tuberculosis, the causative agent of Tuberculosis and a significant cause of infectious disease morbidity and mortality.
Current research themes include:
1:Understanding and exploiting the biological costs of drug-resistance
2:Understanding the interactions between antibiotic targets to design novel combination therapies
3:Identifying strategies to enhance antibiotic lethality
4:Validation of novel drug targets in M. tuberculosis to guide antibiotic development.
This research utilizes a combination of molecular biology, microbiology, antimicrobial susceptibility testing, biochemical assays, next generation sequencing and metabolomics. This work involves the use auxotrophic-avirulent PC2 approved strains of M. tuberculosis, virulent strains of M. tuberculosis that require PC3 containment and the fast-growing model species Mycobacterium smegmatis.
Dr. Will Jowsey
Dr. XinYue Wang
Dr. Cara Adolph
Current post graduate students (Co-Supervised)
Former post graduate students (Co-Supervised)
HRC-NZ Project Grant (2022-2025)
Targeting metabolic dysregulation to eradicate drug resistant M. tuberculosis
$1,199,544 (Principal Investigator)
Sir Charles Hercus Fellowship (HRC-NZ) (2022-2026)
Dysregulating metabolism to eradicate drug-resistant Mycobacterium tuberculosis
$582,826 (Principal Investigator)
Marsden-Project (Royal Society of New Zealand) (2021-2024)
How does allostery modulate bacterial pathogenesis?
$939,000 (Associate Investigator)
China-Maurice Wilkins Centre Collaborative Research Programme (2021-2023)
Exploiting synergistic interaction in energy metabolism to combat drug resistant pathogens
$527,253 (Co-Principal Investigator)
HRC-NSFC Biomedical Collaboration Fund-Project (2020-2023)
Targeting succinate metabolism to produce new chemotherapeutic agents
$699,695 (Associate Investigator)
HRC-NZ Project Grant (2020-2023)
Combatting antimicrobial resistance with high throughput bacterial genetics
$1,199,272 (Principal Investigator)
Maurice Wilkins Centre Flexible Research Grant: Category 2 (2019-2021)
Exploring synthetically lethal interaction in mycobacterial bioenergetics
$9000 (Principal Investigator)
Maurice Wilkins Centre Flexible Research Grant: Category 2. (2019-2021)
Genetic characterisation of drug resistant M. tuberculosis to guide the therapeutic exploitation of collateral susceptibilities
$24000 (Principal Investigator)
Marsden Fast Start (Royal Society of New Zealand) (2018-2021)
Exploiting the costs of drug resistance to design new therapeutic regimens against M. tuberculosis
$300,000 (Principal Investigator)
HRC-NZ Programme Grant (2018-2020)
Targeting pathogen energetics to produce new antimicrobials.
Partial funding for years 1-2, $1,000,000 (Associate Investigator)
2015-2018: Postdoctoral Scientist, Infectious Disease Research Institute, Seattle, USA.
2013-2015: Postdoctoral Scientist, Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
2012-2013: Postdoctoral Scientist, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
With MSc student Natalie Waller
Google Scholar: https://scholar.google.co.nz/citations?user=aI1eYDsAAAAJ&hl=en
* Denotes joint first author. # Denotes corresponding Author
Waller NJE, Cheung CY, Cook GM, McNeil MB#. 2023. The evolution of antibiotic resistnce is associated with collateral drug phenotypes in Mycobacterium tuberculosis. Nature Communications. 14(1). 1517.
Berube BJ, Larsen SE, McNeil MB, Reese VA, Pecor T, Kaur S, Parish T, Baldwin SL, Coler RN. 2022. Characterizing in vivo loss of virulence of an HN878 Mycobacterium tuberculosis isolate from a genetic duplication event. Tuberculosis (Edinb). Dec;137:102272.
McNeil MB#, Cheung CY, Waller NJE, Adolph C, Chapman CL, Seeto NEJ, Jowsey W, Li Z, Hameed HMA, Zhang T, Cook GM. 2022. Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis. Front Cell Infect Microbiol. Aug 24;12:980844.
Adolph C, McNeil MB, Cook GM. 2022. Impaired Succinate Oxidation Prevents Growth and Influences Drug Susceptibility in Mycobacterium tuberculosis. mBio. Jul 20:e0167222.
Harold LK, Jinich A, Hards K, Cordeiro A, Keighley LM, Cross A, McNeil MB, Rhee K, Cook GM. 2022. Deciphering functional redundancy and energetics of malate oxidation in mycobacteria. J Biol Chem. 2022 May;298(5)
Hards K, Cheung CY, Waller N, Adolph C, Keighley L, Tee ZS, Harold LK, Menorca A, Buckley BJ, Tyndall JDA, McNeil MB, Rhee KY, Opel-Reading HK, Krause K, Preiss L, Langer JD, Meier T, Kelso MJ and Cook GM. 2022. An amiloride derivative is active against the F1Fo-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis. Communications Biology. Accepted-In press.
Shelton C, McNeil MB, Allen R, Flint L, Russell D, Berube B, Korkegian A, Ovechkina Y, and Parish T. 2022. Triazolopyrimidines target aerobic respiration in Mycobacterium tuberculosis. AAC. 66(4):e0204121.
Cheung CY, McNeil MB# and Cook GM. 2022. Utilization of CRISPR interference to investigate the contribution of genes to pathogenesis in a macrophage model of Mycobacterium tuberculosis infection. Journal of Antimicrobial Chemotherapy. 77(3):615-619.
McNeil MB#, Ryburn HW, Tirados J, Cheung CY and Cook GM. 2021. Multiplexed transcriptional repression identifies a network of bactericidal interaction between mycobacterial respiratory complexes. iScience. Online ahead of print.
McNeil MB#, Keighley LM, Cook JR, Cheung CY and Cook GM. 2021. CRISPR interference identifies vulnerable cellular pathways with bactericidal phenotypes in Mycobacterium tuberculosis. Molecular Microbiology. 116(4). 1033-1043.
Hembre E, Early JV, Odingo J, Shelton C, Anoshchenko O, Guzman J, Flint L, Dennison D, McNeil MB, Korkegian A, Ovechkina Y, Ornstein P, Masquelin T, Hipskind PA and Parish T. 2021. Novel trifluoromethyl pyrimidinone compounds with activity against Mycobacterium tuberculosis. Frontiers in Chemistry, 9. 176.
Shelton C, McNeil MB, Early J, Ieorger T and Parish T. 2021. Deletion of Rv2571c confers resistance to arylamide compounds in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy. 65(5):e02334-20.
McNeil MB, O’Malley T, Dennison D, Shelton CD, Sundae B and Parish T. 2020. Multiple mutations in Mycobacterium tuberculosis MmpL3 increase resistance to MmpL3 inhibitors. mSphere.5(5).e00985-20.
McNeil, MB#. Ryburn, H. Harold, LK. Tirados, J. andCook, GM. 2020. Transcriptional inhibition of the F1F0-type ATP synthase has bactericidal consequences on the viability of mycobacteria. Antimicrobial Agents and Chemotherapy. 64(8).e00492-20
Shao M, McNeil MB, Cook GM and Lu X. 2020. MmpL3 inhibitors as antituberculosis drugs. European Journal of Medicinal Chemistry. 200:112390..
Hards, K. Adolph, C. Harold, LK. McNeil, MB. Cheung, CY. Jinich, A. Rhee, KY. and Cook, GM. 2019. Two for the price of one: Attacking the energetic-metabolic hub of mycobacteria to produce new chemotherapeutic agents. Prog Biophys Mol Biol. 13.
McNeil MB# and Cook GM. 2019. Utilization of CRISPR interference to validate MmpL3 as a drug target in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy. 63(8)
McNeil MB, Chettiar S, Awasthi D and Parish T. 2019. Cell wall inhibitors increase the accumulation of rifampicin in Mycobacterium tuberculosis. Access Microbiology. 1(1).
Robertson GT, Ektnitphong VA, Scherman MS, McNeil MB + 13 Authors and Lenaerts AJ. 2019. Efficacy and improved resistance potential of a cofactor-independent InhA inhibitor of Mycobacterium tuberculosis in a C3HeB/FeJ mouse model with advanced lung pathology. Antimicrobial Agents and Chemotherapy. 63(4).
Xia Yi, Zhou Y, Carter DS, McNeil MB + 19 Authors and Alley MRK. 2018. Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA. Life Science Alliance. 1(3). e20180025.
McNeil MB, Dennison D, Shelton C, Flint L, Korkegian A and Parish T. 2017. Mechanisms of resistance against NITD-916, a direct inhibitor of Mycobacterium tuberculosis InhA. Tuberculosis.107. 133-136.
McNeil MB, Dennison D, Shelton C and Parish T. 2017. In vitro isolation and characterisation of oxazolidinone resistant Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy.61(10). e01296-17.
McNeil MB, Dennison D and Parish T. 2017. Mutations in MmpL3 alter membrane potential, hydrophobicity and antibiotic susceptibility in Mycobacterium smegmatis. Microbiology. 163. 1065-1070.
Hampton HG, McNeil MB*, Paterson TJ, Ney B, Williamson NR, Easingwood RA, Bostina M, Salmond GP, Fineran PC. 2016. CRISPR-Cas gene-editing reveals RsmA and RsmC act through FlhDC to repress the SdhE flavinylation factor and control motility and prodigiosin production in Serratia. Microbiology. 162(2). 1047-58.
Richter C, Dy RL, Mckenzie RE, Watson BNJ, Taylor C, Chang JT, McNeil MB, Staals RHJ and Fineran PC. 2014. Priming in the Type 1-F CRISPR-Cas system triggers hyperactive strand independent spacer acquisition nearby the primed protospacer. Nucleic Acids Research. 42(13). 8516-26.
McNeil MB, Hampton HG, Hards KJ, Watson BNJ, Cook GM and Fineran PC. 2014. The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. FEBS Letters. 588(3): 414-421.
Fineran PC, +12 other authors. 2013. Draft genome sequence of Serratia sp. strain ATCC 39006, a model bacterium for analysis of the biosynthesis and regulation of prodigiosin, a carbapenem and gas vesicles. Genome Announcements. 1(6): e0139-13.
McNeil MB and Fineran PC. 2013. The conserved RGxxE motif of the bacterial FAD assembly factor SdhE is required for succinate dehydrogenase flavinylation and activity. Biochemistry. 52(43): 7628-7640.
McNeil MB, Iglesias Cans M, Clulow JS and Fineran PC. 2013. YgfX (CptA) is a multimeric membrane protein that interacts with the succinate dehydrogenase assembly factor, SdhE (YgfY). Microbiology. 159: 1352-1365.
McNeil MB, and Fineran PC. 2012. Prokaryotic assembly factors for the attachment of flavins to complex II. BBA Bioenergetics. 1827(5): 637-647.
McNeil MB, Clulow JS, Wilf N, Salmond GPC and Fineran PC. 2012. SdhE is a conserved protein required for the flavinylation of succinate dehydrogenase in bacteria. Journal of Biological Chemistry. 287(22): 18418-18428.
Gristwood T, McNeil MB, Clulow JS, Salmond GPC and Fineran PC. 2011. PigS and PigP Regulate Prodigiosin Biosynthesis in Serratia via Differential Control of Divergent Operons, Which Include Predicted Transporters of Sulfur-Containing Molecules. Journal of Bacteriology. 193:1076-1085.