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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge

Studying at Cambridge

 

Dr Mark A Holmes MA, VetMB, PhD, FRCVS

Dr Mark A Holmes, MA, VetMB, PhD, FRCVS

Reader in Microbial Genomics & Veterinary Science

Director of Studies in Clinical Veterinary Medicine (Churchill College)

Mark Holmes is accepting applications for PhD students.

Mark Holmes is available for consultancy.

Dept of Veterinary Medicine
Madingley Road

Cambridge , Cambs CB3 0ES
Office Phone: +44 1223 337636

Biography:

Education:

Ph.D. in Veterinary Immunology. University of Cambridge. 1989

M.A. University of Cambridge 1986

Vet.MB. University of Cambridge 1985

B.A. Medical Sciences (Pt I) and Computer Science (Pt I). University of Cambridge 1982

Posts held:

2014 to date. Reader in Microbial Genomics & Veterinary Medicine, University of Cambridge.

1999 to 2014. Senior Lecturer in Preventive Veterinary Medicine, University of Cambridge.

1990 – 1999 Lecturer in Preventive Veterinary Medicine, University of Cambridge

Responsible for teaching production animal medicine, cattle medicine, epidemiology, veterinary immunology, statistics, and clinical research methodology.

Director of the Cambridge Infectious Disease Consortium Outreach Program.

Supervision of 8 successful PhD students

2001 TVI during FMD outbreak based in Bury St Edmunds and Exeter

1989-1990: Post doctoral research assistant working on a project entitled “COPD- The role of the immune system and treatment by immunotherapy”

1986-1989: Wellcome Trust Veterinary Research Training Scholar University of Cambridge

1985-1986:  Mixed veterinary practice in Lancashire.

Current and recent grants:

Investigation of livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) in China and the UK (with Dr Andrew Grant, Dr Dan Tucker, Prof Rui Zhou, Dr Shaowen Li, Dr Lu Li) UK-China AMR Partnership Initiative (MR/P007201/1) July 2016 to June 2019 £783,728

Investigation of the population structure and genomic diversity of antibiotic resistant Staphylococcus aureus isolates from livestock in Ghana (PI Dr Beverly Ejyir) Caprex Fellowship and Cambridge-Africa Alborado Research Fund award. July 2016 to December 2017 £20,000 & £17,182.

Refurbishment of space for an initiative on Novel Approaches to Targeting Zoonotic Bacterial Infections (PI Prof Clare Bryant, co-Is: Maskell, Wood, Grant, Tucker), £187,200 Royal Society Wolfson Laboratory Refurbishment Scheme (WL150047) 2016-2017

Cambridge Enterprise ‘Fast Fifty’ seed funds for commercial collaboration with Royal Botanic Gardens, Kew to identify novel antibiotics in plan extracts (with Prof Duncan Maskell and Prof Clare Bryant, Dr Monique Symmonds) March 2016, £50,000

Determination of the dynamics of antimicrobial resistance genes in the human and animal gut microbiome (with Prof Duncan Maskell, Prof Sharon Peacock, Prof Mark Stevens, Prof James Wood, Dr Olivier Restif, Dr Dan Tucker & Dr Andrew Grant) funded by MRC (MR/N002660/1) October 2015 to September 2018 £1,985,599.

Health Protection Research Unit (Healthcare-associated Infections and Antimicrobial Resistance) Research into livestock-associated AMR (Cambridge project) funded by National Institute for Health Research (RG79375). April 2014 to March 2019£15,000

Whole genome sequencing to gain insight into the molecular epidemiology, antibiotic resistance and virulence of Pseudomonas aeruginosa causing canine otitis externa and media infections. £4,275, Petplan Charitable Trust S14-52 2014-15 (with E.M. Harrison).

Identification of biofilms in chronic wound granulation tissue in small animals. £1,545. PetSavers 40th Anniversary Award 2014- 2015 (with PI Ms. J. Ladlow and Dr A. Grant).

Workshop on the use of molecular epidemiology and functional genomics to underpin the development of novel interventions to combat bovine Staphylococcus aureus mastitis in India, £15,000, Royal Society, 2013-14 (with Dr B.K. Shome)

Phenotypic and genomic analysis of antimicrobial resistance in Staphylococcus aureus from UK dairy cattle, £5,290, British Society for Antimicrobial Chemistry, 2013-14 (with G.K. Paterson)

Genome sequencing to understand the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Tanzania. £5,400, Cambridge-Africa Research Fund 2013-14 (with G.K. Paterson)

Bacterial genome sequencing to understand S. aureus infections in rabbits. £4,820, Petplan Charitable Trust 2012-13 (with G.K. Paterson)

Partnership to investigate the emergence of MRSA clones in cattle and their transmission to man (with Prof Ruth Zadoks, Prof Sharon Peacock, & Prof Julian Parkhill) G1001787/1 funded by MRC April 2011 to Dec 2015 £1,500,027

Investigation of a novel Staphylococcus aureus isolate (OD2030) funded by Defra, 2009 – 2010 £71,207 15. Investigation of a novel Staphylococcus aureus isolate funded by Isaac-Newton Trust 2009-2010 £40,000

Departments and Institutes

Consortium Members and Partners:
Veterinary Medicine:
Snr Lecturer in Preventive Veterinary Medicine, Director of the CIDC Clinical Research Outreach Programme

Research Interests

Mark Holmes leads a research group whose current focus of research is on antimicrobial resistance. His lab was responsible for the discovery of a new livestock-associated MRSA harboring a mecA homologue (now named mecC). The new MRSA was discovered during an epidemiological project looking at the transmission of S. aureus in dairy cows by one of our PhD students, Laura Garcia Alvarez. The original isolate was whole genome sequenced and analysed in collaboration with the Wellcome Trust Sanger Institute by Matt Holden and colleagues. We subsequently obtained funding from Defra and the MRC to investigate the discovery further. We are currently undertaking studies to establish the prevalence and diversity of the new MRSA using whole genome sequencing and other techniques. In a collaboration with Prof Alexander Tomasz’s lab at Rockefeller University we have also looked at the function of the PBP2a produced by the mecC gene.

This work is funded by the BBSRC, Defra, and the MRC.

We are currently holding large grants to work on livestock associated MRSA in the UK and China, and on investigations of the dynamics of antimicrobial resistance genes in complex bacterial populations.

Mark Holmes also has interests in clinical research (including animal welfare) and evidence-based veterinary medicine and has published a number of papers and books in these areas.

Keywords

  • Molecular epidemiology
  • Evolution
  • Sequencing
  • Immunology
  • Dairy Cows
  • Gene Expression
  • Phylogenetics
  • Vaccine development
  • Infection
  • Epidemiology
  • Veterinary Science
  • Bioinformatics
  • Bacteriology
  • Immunopathogenesis
  • Antibody
  • Gene Regulation

Topics

  • MRSA
  • Staphylococcus aureus
  • Zoonoses

Key Publications

Harrison EM, Ludden C, Brodrick HJ, Blane B, Brennan G, Morris D, Coll F, Reuter S, Brown NM, Holmes MA, O’Connell B, Parkhill J, Török EM, Cormican M and Peacock SJ. Transmission of methicillin-resistant Staphylococcus aureus in long-term care facilities and their related healthcare networks. Genome Medicine 2016 8:102. DOI: 10.1186/s13073-016-0353-5

Mather AE, Lawson B, de Pinnac E, Wigley P, Parkhill J, Thomson NR, Page AJ, Holmes MA Paterson GK. Genomic analysis of Salmonella enterica serovar Typhimurium from wild passerines in England and Wales. Applied and Environmental Microbiology online 9 September 2016, doi: 10.1128/AEM.01660-16 Holmes MA, Harrison EM, Fisher EA, Graham EM, Parkhill J,

Foster G, et al. (2016) Genomic Analysis of Companion Rabbit Staphylococcus aureus. PLoS ONE 11(3): e0151458. doi:10.1371/journal.pone.0151458 Semmler T,

Harrison EM, Lübke-Becker A, Ulrich RG, Wieler LH, Guenther S, Stamm I, Hanssen AM, Holmes MA, Vincze S, Walther B. A look into the melting pot: The mecC-harboring region is a recombination hot spot in Staphylococcus stepanovicii. PLoS One. 2016 Jan 22;11(1):e0147150. doi: 10.1371/journal.pone.0147150.

Harrison EM, Ba X, Blane B, Ellington M, Loeffler A, Hill R, Holmes MA, Peacock SJ. PBP2a substitutions linked to ceftaroline resistance in MRSA isolates from the United Kingdom. J Antimicrob Chemother. 2015 Oct 12. pii: dkv317. [Epub ahead of print]

Ba X, Harrison EM, Lovering A, Gleadall N, Parkhill J, Zadoks RN, Peacock SJ, Holden MTG, Paterson GK, and Holmes MA. Old drugs to treat resistant bugs: methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid. 21 September 2015, Antimicrob. Agents Chemother. doi:10.1128/AAC.01469-15

Murray GG, Wang F, Harrison EM, Paterson GK, Mather AE, Harris SR, Holmes MA, Rambaut A, Welch JJ. The effect of genetic structure on molecular dating and tests for temporal signal. Methods in Ecology and Evolution 22 Sep 2015. DOI: 10.1111/2041-210X.12466

Hahn C, Harrison EM, Parkhill J, Holmes MA, Paterson GK. Draft Genome Sequence of the Streptococcus pneumoniae Avery Strain A66. Genome Announc. May/June 2015 vol. 3 no. 3 e00697-15. doi: 10.1128/genomeA.00697-15

Hadjirin NF, Lay EM, Paterson GK, Harrison EM, Peacock SJ, Herrtage ME, Parkhill J, Holmes MA. Detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in retail pork, United Kingdom, February 2015. Euro Surveill. 2015 Jun 18;20(24)

Aiken MJ, Hughes TK, Abercromby RH, Holmes MA, Anderson AA. Prospective, Randomized Comparison of the Effect of Two Antimicrobial Regimes on Surgical Site Infection Rate in Dogs Undergoing Orthopedic Implant Surgery. Vet Surg. 2015 Jul;44(5):661-7. doi: 10.1111/vsu.12327. Epub 2015 Mar 17.

Paterson GK, Harrison EM, Murray GGR, Welch JJ, Warland JH, Holden MTG, Morgan FJE, Ba X, Koop G, Harris S, Maskell DJ, Peacock SJ, Herrtage ME, Parkhill J, Holmes MA. Capturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission. Nat. Commun. 6:6560 doi: 10.1038/ncomms7560 (2015).

Espinosa-Gongora C, Harrison, E, Moodley A, Guardabassi L, Holmes MA. Methicillin-resistant Staphylococcus aureus carrying mecC in captive mara. J Antimicrob Chemother 2015 Feb 25. doi:10.1093/jac/dkv024

Larsen A, Petersen A, Holmes MA; Kearns A, Hill R, Edwards G, Teale C, Skov R. Utility of a newly developed Muller Hinton E agar for the detection of MRSA carrying the novel mecA homologue mecC. J Antimicrob Chemother 2015 Apr;70(4):1256-7. doi: 10.1093/jac/dku512. Epub 2014 Dec 23

McCarthy AJ, Harrison EM, Stanczak-Mrozek K, Leggett B, Waller A, Holmes MA, Lloyd DH, Lindsay JA, Loeffler A. Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius. J Antimicrob Chemother. 2015 Apr;70(4):997-1007. doi: 10.1093/jac/dku496. Epub 2014 Dec 18

Kerschner H, Harrison EM, Hartl R, Holmes MA and Apfalter P. First report of mecC MRSA in human samples from Austria: molecular characteristics and clinical data. New Microbe and New Infect 2015; 3: 4–9

Porrero MC, Harrison EM, Fernández-Garayzabal JF, Paterson GK, Díez- Guerrier A, Holmes MA, Domínguez L Detection of mecC-river water: a potential role for water in the environmental dissemination. Environmental Microbiology Reports 2014 July 14 DOI:10.1111/1758-2229.12191

Prenafeta A, Sitjà M, Holmes MA, Paterson GK. Short communication: Biofilm production characterization of mecA and mecC methicillin-resistant Staphylococcus aureus isolated from bovine milk in Great Britain. J Dairy Sci. 2014 Aug;97(8):4838-41. doi: 10.3168/jds.2014-7986. Epub 2014 Jun 2.

Harrison EM, Weinert LA, Holden MT, Welch JJ, Wilson K, Morgan FJ, Harris SR, Loeffler A, Boag AK, Peacock SJ, Paterson GK, Waller AS, Parkhill J, Holmes MA. A Shared Population of Epidemic Methicillin-Resistant Staphylococcus aureus 15 Circulates in Humans and Companion Animals. MBio. 2014 May 13;5(3). pii: e00985-13. doi: 10.1128/mBio.00985-13.

Christiansen MT, Kaas RS, Chaudhuri RR, Holmes MA, Hasman H, et al. (2014) Genome-Wide High-Throughput Screening to Investigate Essential Genes Involved in Methicillin-Resistant Staphylococcus aureus Sequence Type 398 Survival. PLoS ONE 9(2): e89018. doi:10.1371/journal.pone.0089018

Hadjirin NF, Harrison EM, Holmes MA, Paterson GK. Conjugative transfer frequencies of mef(A) containing Tn1207.3 to macrolide susceptible Streptococcus pyogenes belonging to different emm types. Lett Appl Microbiol. 2014 Jan 3. doi: 10.1111/lam.12213.

Paterson GK, Morgan FJ, Harrison EM, Cartwright EJ, Török ME, Zadoks RN, Parkhill J, Peacock SJ, Holmes MA. Prevalence and characterization of human mecC methicillin-resistant Staphylococcus aureus isolates in England. J Antimicrob Chemother. 2014 Apr;69(4):907-10. doi: 10.1093/jac/dkt462. Epub 2013 Nov 27.

Paterson GK, Harrison EM, Holmes MA. The emergence of mecC methicillin-resistant Staphylococcus aureus. Trends Microbiol. 2014 Jan;22(1):42-7. doi: 10.1016/j.tim.2013.11.003. Epub 2013 Dec 9.

Hall JL, Holmes MA, Baines SJ. Prevalence and antimicrobial resistance of canine urinary tract pathogens. Vet Rec. 2013 Dec 7;173(22):549. doi: 10.1136/vr.101482. Epub 2013 Oct 24.

Paterson GK, Morgan FJE, Harrison EM, Peacock SJ, Parkhill J, Zadoks RN and Holmes MA. Prevalence and properties of mecC methicillin-resistant Staphylococcus aureus (MRSA) in bulk tank milk in Great Britain. J Antimicrob Chemother. 2014 Mar;69(3):598-602. doi: 10.1093/jac/dkt417. Epub 2013 Oct 23.

Harrison EM, Paterson GK, Holden MTG, Ba X, Rolo J, Morgan FJE, Pichon B, Kearns A, Zadoks RN, Peacock SJ, Parkhill J, Holmes MA. A novel hybrid SCCmec-mecC region in Staphyloccus sciuri. J Antimicrob Chemother. 2014 Apr;69(4):911-8. doi: 10.1093/jac/dkt452. Epub 2013 Dec 2.

Ba X, Harrison EM, Edwards GF, Holden MTG, Rhod Larsen A, Petersen A, Skov RL, Peacock SJ, Parkhill J, Paterson GK, Holmes MA. Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin-resistant on susceptibility testing but lack the mec gene. J Antimicrob Chemother. 2014 Mar;69(3):594-7. doi: 10.1093/jac/dkt418. Epub 2013 Nov 11.

Skov R, Larsen AR, Kearns A, Holmes MA; Teale C, Hill R. Phenotypic detection of mecC-MRSA: Cefoxitin is more reliable than oxacillin. J Antimicrob Chemother. 2013 doi:10.1093/jac/dkt341 published online 12 Sep 13

Paterson GK, Harrison EM, Craven EF, Petersen A, Larsen AR, Ellington MJ, Török ME, Peacock SJ, Parkhill J, Zadoks RN, Holmes MA. Incidence and characterisation of methicillin-resistant Staphylococcus aureus (MRSA) from nasal colonisation in participants attending a cattle veterinary conference in the UK. PLoS ONE 8(7): e68463. doi:10.1371/journal.pone.0068463

Cartwright EJ, Paterson GK, Raven KE, Harrison EM, Gouliouris T, Kearns A, Pichon B, Edwards G, Skov RL, Larsen AR, Holmes MA, Parkhill J, Peacock SJ, Török ME. Use of VITEK 2 antimicrobial susceptibility profile to identify mecC in methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2013 May 29.

Harrison EM, Paterson GK, Holden MT, Larsen J, Stegger M, Larsen AR, Petersen A, Skov RL, Christensen JM, Bak Zeuthen A, Heltberg O, Harris SR, Zadoks RN, Parkhill J, Peacock SJ, Holmes MA. Whole genome sequencing identifies zoonotic transmission of MRSA isolates with the novel mecA homologue mecC. EMBO Mol Med. 2013 Apr;5(4):509-15. doi: 10.1002/emmm.201202413.

Becker K, Larsen AR, Skov RL, Paterson GK, Holmes MA, Sabat AJ, Friedrich AW, Köck R, Peters G, Kriegeskorte A. Evaluation of a Modular Multiplex-PCR Methicillin-Resistant Staphylococcus aureus Detection Assay Adapted for mecC Detection. J Clin Microbiol. 2013 Jun;51(6):1917-9. doi: 10.1128/JCM.00075-13.

Harrison EM, Paterson GK, Holden MTG, Morgan FEJ, Rhod Larsen A, Leroy S, Zadoks RN, Peacock SJ, Parkhill J, Holmes MA. A Staphyloccocus xylosus isolate with a new mecC allotype provides insights into the evolutionary origins of the type XI SCCmec. Antimicrob Agents Chemother. 2013 Mar;57(3):1524-8. doi: 10.1128/AAC.01882-12.

Paterson GK, Larsen J, Harrison EM, Larsen AR, Morgan FJ, Peacock SJ, Parkhill J, Zadoks RN, Holmes MA. First detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012. Euro Surveill. 2012

Kim C, Milheiriço C, Gardete D, Holmes MA, Holden MTG, de Lencastre H, and Tomasz A. Properties of a novel PBP2A protein homologue from Staphylococcus aureus strain LGA251 and its contribution to the β-lactam resistant phenotype. 2012 J. Biol. Chem [ePub ahead of print].

Paterson GK, Larsen AR, Robb A, Edwards GE, Pennycott TW, Foster G, Mot D, Hermans K, Baert K, Peacock SJ, Parkhill J, Zadoks RN, Holmes MA. The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species. J Antimicrob Chemother. 2012 Aug 31. [Epub ahead of print]

Pichon B, Hill R, Laurent F, Larsen AR, Skov RL, Holmes M, Edwards GF, Teale C, Kearns AM. Development of a real-time quadruplex PCR assay for simultaneous detection of nuc, Panton-Valentine leucocidin (PVL), mecA and homologue mecALGA251. J Antimicrob Chemother. 2012 Jun 11. [Epub ahead of print]

Stegger, M., Andersen, P. S., Kearns, A., Pichon, B., Holmes, M. A., Edwards, G., Laurent, F., Teale, C., Skov, R., Larsen, A. R. Rapid detection, differentiation and typing of methicillin-resistant Staphylococcus aureus harbouring either mecA or the new mecA homologue mecA(LGA251). Clin Microbiol Infect 2012 18:4 395-400

Holmes, M.A. & Zadoks, R.N. Methicillin resistant S. aureus in human and bovine mastitis. J Mammary Gland Biol Neoplasia. 2011 Dec;16(4):373-82.

García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD, et al. A descriptive study of MRSA harbouring a novel mecA homologue emerging in human and bovine populations in the United Kingdom and Denmark. Lancet Infect Dis. 2011 Aug;11(8):595-603

Alvarez LG, Webb CR, Holmes MA. A novel field-based approach to validate the use of network models for disease spread between dairy herds. Epidemiol Infect. 2011:Feb 1-12.

Lucianez A, Holmes MA, Tucker AW. Relationships between Processing Delay and Microbial Load of Broiler Neck Skin Samples. J Food Prot. 2010; 73(1): 26-31.