Dr Suzie Hingley-Wilson

Research Interests

My primary research interests are tuberculosis (TB) and anti-microbial resistance (AMR). We conduct multidisciplinary research, much at the single cell level, looking at antimicrobial resistance and persistence often in the context of the host cell. We aim to identify novel mechanisms and immunotherapeutic targets by taking a global approach utilising microfluidics, mycobacterial mutagenesis, patient and environmental samples. In our lab we believe that by taking the average you often miss out the exceptional.

TB and AMR remain major global health problems. The causative agent of TB, Mycobacterium tuberculosis, can survive, replicate and persist within the toxic intracellular environment of our own immune cells and my research career has focused on elucidating the mechanisms responsible. We are currently working on how exposure to the host alters bacterial AMR and are also setting up a correlating drug screen to target and reduce AMR and TB.

Single cell studies of Mycobacterium tuberculosis. Left) Mycobacteria treated with the front-line antibiotic rifampicin (x400). While the majority of the mycobacterial population have been killed by the anti-TB drug rifampicin (red-dead) a small minority of antibiotic-tolerant mycobacterial persisters (green) survive, able to repopulate once the antibiotic is removed. This persister population is responsible for treatment failure in numerous bacterial diseases. Right) an electron micrograph of a human macrophage we have infected with the intracellular pathogen Mtb (arrows, x6000).

Teaching

I teach on the bacteriology practicals (Undergraduate) and on the Masters in Medical Microbiology (including host-pathogen entry and intelligent experimental design). I also supervise undergraduate and postgraduate projects and am a Fellow of the Higher Education Academy.

Affiliations

I am a member of the Acid Fast Club, the Society of General Microbiology and British Society of Immunology and a Springboard and Aurora Leadership development course graduate.

Contact Me

E-mail:

My office hours

Monday-Friday

Publications

Journal articles

  • Upton N, Jackson D, Nikonova A, Hingley-Wilson S, Khaitov M, Del Rosario A, Traub S, Trujillo-Torralbo M, Habibi M, Elkin S, Kon O, Edwards M, Mallia P, Footitt J, Macintyre J, Stanciu L, Johnston S, Sykes A. (2017) 'Rhinovirus induction of fractalkine (CX3CL1) in airway and peripheral blood mononuclear cells in asthma'. Public Library of Science PLoS One, 12 (8) Article number e0183864 , pp. 1-13.

    Abstract

    Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P<0.01) and in M1-polarised macrophages (P<0.05), but not in BAL cells from mild asthmatics or in M2 polarised macrophages. Rhinovirus induced fractalkine in PBMCs from asthmatic (P<0.001) and healthy control subjects (P<0.05). Trends towards induction of fractalkine in moderate asthmatic subjects during in vivo rhinovirus infection failed to reach statistical significance. Fractalkine may be involved in both immunopathological and anti-viral immune responses to rhinovirus infection. Further investigation into how fractalkine is regulated across different cell types and into the effect of stimulation including rhinovirus infection is warranted to better understand the precise role of this unique dual adhesion factor and chemokine in immune cell recruitment.

  • Hu Y, Wang S, Ma N, Hingley-Wilson S, Rocco A, McFadden J, Tang H. (2017) 'Trajectory Energy Minimisation for Cell Growth Tracking and Genealogy Analysis'. The Royal Society Royal Society Open Science, 4 Article number 170207

    Abstract

    Cell growth experiments with a microfluidic device produce large scale time-lapse image data, which contain important information on cell growth and patterns in their genealogy. To extract such information, we propose a scheme to segment and track bacterial cells automatically. In contrast to most published approaches, which often split segmentation and tracking into two independent procedures, we focus on designing an algorithm that describes cell properties evolving between consecutive frames by feeding segmentation and tracking results from one frame to the next one. The cell boundaries are extracted by minimising the Distance Regularised Level Set Evolution model. Each individual cell was identified and tracked by identifying cell septum and membrane as well as developing a trajectory energy minimisation function along time-lapse series. Experiments show that by applying this scheme, cell growth and division can be measured automatically. The results show the efficiency of the approach when testing on different datasets while comparing with other existing algorithms. The proposed approach demonstrates great potential for large scale bacterial cell growth analysis.

  • Hingley-Wilson S, Connell D, Pollock K, Grass L, Potiphar L, Bremang S, Lalvani A, Hsu T, Jacobs Jr W, Tchilian E, Sykes A, Kon O. (2014) 'ESX1-dependent fractalkine mediates chemotaxis and Mycobacterium tuberculosis infection in humans'. Tuberculosis, 94 (3), pp. 262-270.

    Abstract

    Mycobacterium tuberculosis-induced cellular aggregation is essential for granuloma formation and may assist establishment and early spread of M. tuberculosis infection. The M. tuberculosis ESX1 mutant, which has a non-functional type VII secretion system, induced significantly less production of the host macrophage-derived chemokine fractalkine (CX3CL1). Upon infection of human macrophages ESX1-dependent fractalkine production mediated selective recruitment of CD11b+ monocytic cells and increased infection of neighbouring cells consistent with early local spread of infection. Fractalkine levels were raised in vivo at tuberculous disease sites in humans and were significantly associated with increased CD11b+ monocytic cellular recruitment and extent of granulomatous disease. These findings suggest a novel fractalkine-dependent ESX1-mediated mechanism in early tuberculous disease pathogenesis in humans. Modulation of M. tuberculosis-mediated fractalkine induction may represent a potential treatment option in the future, perhaps allowing us to switch off a key mechanism required by the pathogen to spread between cells. © 2014 The Authors.

  • Hingley-Wilson S, Casey R, Connell D, Bremang S, Evans J, Hawkey P, Smith G, Jepson A, Philip S, Kon O, Lalvani A. (2013) 'Undetected Multidrug-Resistant Tuberculosis Amplified by First-line Therapy in Mixed Infection'. CENTERS DISEASE CONTROL EMERGING INFECTIOUS DISEASES, 19 (7), pp. 1138-1141.

    Abstract

    Infections with >1 Mycobacterium tuberculosis strain(s) are underrecognized. We show, in vitro and in vivo, how first-line treatment conferred a competitive growth advantage to amplify a multidrug-resistant M. tuberculosis strain in a patient with mixed infection. Diagnostic techniques that identify mixed tubercle bacilli populations are needed to curb the spread of multidrug resistance.

  • Pareek M, Evans J, Innes J, Smith G, Hingley-Wilson S, Lougheed KE, Sridhar S, Dedicoat M, Hawkey P, Lalvani A. (2013) 'Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype'. Thorax, 68 (3), pp. 221-229.
  • Hingley-Wilson SM. (2013) 'Metagenomic analysis of tuberculosis - Current limitations'. New England Journal of Medicine, 369 (16)
  • Pareek M, Hingley-Wilson S, Sridhar S, Lalvani A, Evans J, Smith G, Hawkey P, Innes J, Dedicoat M, Lougheed KE. (2012) 'Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype'. Thorax,
  • Trauner A, Lougheed KEA, Bennett MH, Hingley-Wilson SM, Williams HD. (2012) 'The dormancy regulator DosR controls ribosome stability in hypoxic mycobacteria'. Journal of Biological Chemistry, 287 (28), pp. 24053-24063.
  • Thillai M, Eberhardt C, Lewin AM, Potiphar L, Hingley-Wilson S, Sridhar S, Macintyre J, Kon OM, Wickremasinghe M, Wells A, Weeks ME, Mitchell D, Lalvani A. (2012) 'Sarcoidosis and tuberculosis cytokine profiles: indistinguishable in bronchoalveolar lavage but different in blood.'. PLoS One, United States: 7 (7)
  • Montamat-Sicotte DJ, Millington KA, Willcox CR, Hingley-Wilson S, Hackforth S, Innes J, Kon OM, Lammas DA, Minnikin DE, Besra GS, Willcox BE, Lalvani A. (2011) 'A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection.'. J Clin Invest, United States: 121 (6), pp. 2493-2503.
  • Millington KA, Fortune SM, Low J, Garces A, Hingley-Wilson SM, Wickremasinghe M, Kon OM, Lalvani A. (2011) 'Rv3615c is a highly immunodominant RD1 (Region of difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection'. Proceedings of the National Academy of Sciences of the United States of America, 108 (14), pp. 5730-5735.
  • Süzgeaç-Selaçuk S, Meriaçli AH, Güven KC, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Tasdemir D. (2011) 'Evaluation of Turkish seaweeds for antiprotozoal, antimycobacterial and cytotoxic activities'. Phytotherapy Research, 25 (5), pp. 778-783.
  • Broniatowska B, Allmendinger A, Tasdemir D, Kaiser M, Montamat-Sicotte D, Hingley-Wilson S, Lalvani A, Guiry M, Blunden G. (2011) 'Antiprotozoal, antitubercular and cytotoxic potential of cyanobacterial (blue-green algal) extracts from Ireland'. Natural Product Communications, 6 (5), pp. 689-694.
  • Spavieri J, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Blunden G, Tasdemir D. (2010) 'Antiprotozoal, antimycobacterial and cytotoxic potential of some British green algae'. Phytotherapy Research, 24 (7), pp. 1095-1098.
  • Allmendinger A, Spavieri J, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Guiry M, Blunden G, Tasdemir D. (2010) 'Antiprotozoal, antimycobacterial and cytotoxic potential of twenty-three British and Irish red algae'. Phytotherapy Research, 24 (7), pp. 1099-1103.
  • Spavieri J, Allmendinger A, Kaiser M, Casey R, Hingley-Wilson S, Lalvani A, Guiry MD, Blunden G, Tasdemir D. (2010) 'Antimycobacterial, antiprotozoal and cytotoxic potential of twenty-one brown algae (phaeophyceae) from British and Irish waters'. Phytotherapy Research, 24 (11), pp. 1724-1729.
  • Hingley-Wilson SM, Lougheed KEA, Ferguson K, Leiva S, Williams HD. (2010) 'Individual Mycobacterium tuberculosis universal stress protein homologues are dispensable in vitro'. Tuberculosis, 90 (4), pp. 236-244.
  • Lalvani A, Hingley-Wilson S. (2009) 'Editorial: Live or let die--does HIV exacerbate tuberculosis by attenuating M. tuberculosis-induced apoptosis?'. J Leukoc Biol, United States: 86 (1), pp. 9-11.
  • Hingley-Wilson S, Lalvani A. (2008) 'An exit strategy for the tubercle bacillus?'. Nat Rev Microbiol, England: 6 (12)
  • Terry Alli OA, Hingley-Wilson S, Spreadbury Claire L, Terry Alli OA, Ogbolu DO, Hingley-Wilson S. (2008) 'The Mycobacterium tuberculosis homologue of the Mycobacterium avium mig gene is not specifically expressed in the macrophage'. African Journal Biomedical Research, 11 (2), pp. 173-181.
  • Hsu T, Hingley-Wilson S, Chen B, Chen M, Dai A, Morin P, Marks C, Padiyar J, Goulding C, Gingery M, Eisenberg D, Russell R, Derrick S, Collins F, Morris S, King C, Jacobs W. (2003) 'The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue'. National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, 100 (21), pp. 12420-12425.
    [ Status: Accepted ]

    Abstract

    Tuberculosis remains a leading cause of death worldwide, despite the availability of effective chemotherapy and a vaccine. Bacillus Calmette–Guérin (BCG), the tuberculosis vaccine, is an attenuated mutant of Mycobacterium bovis that was isolated after serial subcultures, yet the functional basis for this attenuation has never been elucidated. A single region (RD1), which is absent in all BCG substrains, was deleted from virulent M. bovis and Mycobacterium tuberculosis strains, and the resulting ΔRD1 mutants were significantly attenuated for virulence in both immunocompromised and immunocompetent mice. The M. tuberculosis ΔRD1 mutants were also shown to protect mice against aerosol challenge, in a similar manner to BCG. Interestingly, the ΔRD1 mutants failed to cause cytolysis of pneumocytes, a phenotype that had been previously used to distinguish virulent M. tuberculosis from BCG. A specific transposon mutation, which disrupts the Rv3874 Rv3875 (cfp-10 esat-6) operon of RD1, also caused loss of the cytolytic phenotype in both pneumocytes and macrophages. This mutation resulted in the attenuation of virulence in mice, as the result of reduced tissue invasiveness. Moreover, specific deletion of each transcriptional unit of RD1 revealed that three independent transcriptional units are required for virulence, two of which are involved in the secretion of ESAT-6 (6-kDa early secretory antigenic target). We conclude that the primary attenuating mechanism of bacillus Calmette–Guérin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness.

  • Hingley-Wilson S, Sambandamurthy V, Jacobs W. (2003) 'Survival perspectives from the world's most successful pathogen, Mycobacterium tuberculosis'. Nature Publishing Group Nature Immunology, 4 (10), pp. 949-955.
    [ Status: Accepted ]

    Abstract

    Studying defined mutants of Mycobacterium tuberculosis in the mouse model of infection has led to the discovery of attenuated mutants that fall into several phenotypic classes. These mutants are categorized by their growth characteristics compared with those of wild-type M. tuberculosis, and include severe growth in vivo mutants, growth in vivo mutants, persistence mutants, pathology mutants and dissemination mutants. Here, examples of each of these mutant phenotypes are described and classified accordingly. Defining the importance of mycobacterial gene products responsible for in vivo growth, persistence and the induction of immunopathology will lead to a greater understanding of the host-pathogen interaction and potentially to new antimycobacterial treatment options.

  • Sly L, Hingley-Wilson S, Reiner N, McMaster W. (2003) 'Survival of Mycobacterium tuberculosis in host macrophages involves resistance to apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1'. American Association of Immunologists Journal of Immunology, 70 (1), pp. 430-437.
    [ Status: Accepted ]

    Abstract

    Mcl-1 protein expression was found to be up-regulated during infection with virulent Mycobacterium tuberculosis strain H37Rv. Mcl-1 induction in THP-1 cells was optimal at a multiplicity of infection of 0.8–1.2 bacilli per macrophage and was independent of opsonin coating of the bacteria. Mcl-1 expression was elevated as early as 4 h, peaked at 5.8-fold above control cells at 24 h, and remained elevated at 48 h after infection. In THP-1 cells, mMcl-1 mRNA was induced by infection with live H37Rv but not with attenuated M. tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads. In THP-1 cells and monocyte-derived macrophages (MDMs), Mcl-1 protein was induced by infection with live H37Rv but not with attenuated M. tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads. Treatment of uninfected, H37Ra-infected, and H37Rv-infected THP-1 cells and MDMs with antisense oligonucleotides to mcl-1 reduced Mcl-1 expression by >84%. This resulted in an increase in apoptosis of both MDMs and THP-1 cells that were infected with H37Rv, but not cells that were uninfected or infected with H37Ra. Increased apoptosis correlated with a decrease in M. tuberculosis CFUs recovered from antisense-treated, H37Rv-infected cells at 4 and 7 days after infection. In contrast, CFU recoveries from sense-treated, H37Rv-infected cells or from antisense- or sense-treated, H37Ra-infected cells were unchanged from controls. Thus, the antiapoptotic effect of the induction of Mcl-1 expression in H37Rv-infected macrophages promotes the survival of virulent M. tuberculosis.

Conference papers

  • Hingley-Wilson S, Connell D, Pollock K, Min KO, Jr JW, Lalvani A. (2011) 'Fractalkine production mediates virulence-associated monocyte recruitment and Mycobacterium tuberculosis infection'. IMMUNOLOGY, 135, pp. 167-167.
  • Hingley-Wilson S, Kon OM, Hsu T, Jr JW, Lalvani A. (2010) 'Mycobacterium tuberculosis RD1 is a requisite for virulence-associated cellular recruitment'. IMMUNOLOGY, 131, pp. 173-173.
  • Montamat-Sicotte D, Millington K, Willcox CR, Hingley-Wilson S, Hackforth S, Innes J, Kon OM, Minnikin DE, Besra GS, Willcox BE, Lalvani A. (2010) 'Mycolic acid-specific T-cells in human tuberculosis are dynamically related to antigen load and exhibit memory expansion after cure'. IMMUNOLOGY, 131, pp. 171-171.

Page Owner: sh0035
Page Created: Monday 28 July 2014 09:19:39 by sa0043
Last Modified: Tuesday 2 January 2018 09:54:25 by kj0008
Expiry Date: Wednesday 28 October 2015 09:14:38
Assembly date: Wed Oct 16 00:26:18 BST 2019
Content ID: 129359
Revision: 14
Community: 1196

Rhythmyx folder: //Sites/surrey.ac.uk/Microbial Sciences/People
Content type: rx:StaffProfile