After an initial training in microbiology at the University of Reading, during which I developed an enduring interest in infectious disease and public health, my graduate studies used molecular, genetic, and biochemical techniques to study sugar transport in Escherichia coli with Peter Henderson at the Department of Biochemistry, University of Cambridge. I became interested multi-disciplinary and evolutionary approaches to investigating biological problems and, after a two-year MRC Training Fellowship, I began my independent research career at the National Institute for Biological Standards and Control, where I was a group leader for nine years, including a sabbatical year in Mark Achtman’s laboratory at the Max-Planck-Institut für molekulare Genetik, Berlin. In this period I worked mainly on the biology Neisseria meningitidis and its implications for vaccination. In 1997 I moved to a Wellcome Trust Senior Fellowship in Oxford and was appointed Professor of Molecular Epidemiology and a Fellow of Hertford College in 2004. I became a Fellow of the Royal College of Pathologists in 2010 and a Fellow of the Society of Biology in 2012 .My current work focuses on exploiting genome sequences to characterize structure within populations of pathogens and relating this to phenoytpes of medical importance especially, but not exclusively, working on members of the genera Neisseria and Campylobacter.
Since my PhD, where we identified the major facilitator super family of transporters (1), I have exploited ecological and evolutionary ideas to investigate structure-function relationships with multidisciplinary comparative analyses of bacterial pathogens, translating my research into public health impact at the National Institute for Biological Standards and Control and since 1997 at Oxford.
My group pioneered widely-used approaches for sequence-based analyses including: multi locus sequence typing (MLST) (2), now a textbook method; antigen gene sequencing (3); and web-based databases and analysis tools (4). We demonstrated that, notwithstanding frequent horizontal gene transfer (5), repertoires of highly variable meningococcal antigens are stable over time and geographic spread (3). These repertoires are consistent with strain structure generated by immune responses (6) and are being exploited in vaccine development. We further showed that the associations of particular lineages with invasive phenotypes and antigens (7) are consistent with a conceptual framework that combines selection and competition among strains during transmission, in the context of specific immune responses (8). We have further shown that population effects in meningococcal carriage (9), specifically herd immunity, are crucially important in the effectiveness of protein-polysaccharide conjugate vaccines (10), with transmission differences among strains important in vaccine impact (11). This has been influential in the development of immunisation policy, including for the MenAfriVac (PsA-TT) capsular vaccine recently developed for Africa (12). Whole genome analyses (4), including our novel universal approach, ribosomal MLST (rMLST) (13) are providing new insights into the evolution of Neisseria species (14), meningococcal strains (15), and antigen genes (16).
Our related studies of Campylobacter (17) have transformed the field, leading to improved understanding of the sources of human campylobacteriosis (18), and Campylobacter ecology , population biology and evolution (19), and epidemiology (20).
Some Key References
1. Maiden MCJ, Davis EO, Baldwin SA, Moore DCM, Henderson PJF. 1987. Mammalian and bacterial sugar transport proteins are homologous. Nature 325:641-643.
2. Maiden MCJ, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, Zhang Q, Zhou J, Zurth K, Caugant DA, Feavers IM, Achtman M, Spratt BG. 1998. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA 95:3140-3145.
3. Suker J, Feavers IM, Achtman M, Morelli G, Wang JF, Maiden MCJ. 1994. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation. Mol. Microbiol. 12:253-265.
4. Jolley KA, Maiden MC. 2010. BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 11:595.
5. Holmes EC, Urwin R, Maiden MCJ. 1999. The influence of recombination on the population structure and evolution of the human pathogen Neisseria meningitidis. Mol. Biol. Evol. 16:741-749.
6. Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM, Anderson RM. 1996. The maintenance of strain structure in populations of recombining infectious agents. Nat. Med. 2:437-442.
7. Yazdankhah SP, Kriz P, Tzanakaki G, Kremastinou J, Kalmusova J, Musilek M, Alvestad T, Jolley KA, Wilson DJ, McCarthy ND, Caugant DA, Maiden MC. 2004. Distribution of serogroups and genotypes among disease-associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway. J. Clin. Microbiol. 42:5146-53.
8. Buckee CO, Jolley K, Recker M, Penman B, Kriz P, Gupta S, Maiden MC. 2008. Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis. Proc. Natl. Acad. Sci. USA 105:15082-15087.
9. Jolley KA, Kalmusova J, Feil EJ, Gupta S, Musilek M, Kriz P, Maiden MC. 2002. Carried meningococci in the Czech Republic: a diverse recombining population. J. Clin. Microbiol. 40:3549-3550.
10. Maiden MC, Stuart JM, UK_Meningococcal_Carriage_Group. 2002. Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination. Lancet 359:1829-31.
11. Maiden MC, Ibarz-Pavon AB, Urwin R, Gray SJ, Andrews NJ, Clarke SC, Walker AM, Evans MR, Kroll JS, Neal KR, Ala’aldeen DA, Crook DW, Cann K, Harrison S, Cunningham R, Baxter D, Kaczmarski E, Maclennan J, Cameron JC, Stuart JM. 2008. Impact of Meningococcal Serogroup C Conjugate Vaccines on Carriage and Herd Immunity. J. Infect. Dis. 197:737-743.
12. Doumagoum Moto D, Gami JP, Gamougam K, Naibei N, Mbainadji L, Narbé M, Toralta J, Kodbesse B, Ngadoua C, Coldiron M, Ferman F, Page A-L, Djingarey M, Hugonnet S, Harrison OB, Rebbetts LS, Tekletsion Y, Watkins ER, Caugant DA, Chandramohan D, Hassan-King M, Manigart O, Nascimento M, Woukeu A, Trotter C, Stuart JM, Maiden MCJ, Greenwood B. 2013. The impact of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad. Lancet 383:40-47.
13. Jolley KA, Bliss CM, Bennett JS, Bratcher HB, Brehony CM, Colles FM, Wimalarathna HM, Harrison OB, Sheppard SK, Cody AJ, Maiden MC. 2012. Ribosomal Multi-Locus Sequence Typing: universal characterization of bacteria from domain to strain. Microbiology 158:1005-15.
14. Bennett JS, Jolley KA, Earle SG, Corton C, Bentley SD, Parkhill J, Maiden MC. 2012. A genomic approach to bacterial taxonomy: an examination and proposed reclassification of species within the genus Neisseria. Microbiology 158:1570-80.
15. Jolley KA, Hill DM, Bratcher HB, Harrison OB, Feavers IM, Parkhill J, Maiden MC. 2012. Resolution of a meningococcal disease outbreak from whole genome sequence data with rapid web-based analysis methods. J. Clin. Microbiol. 50:3046-53.
16. Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB, Jolley KA, Corton C, Care R, Poolman JT, Zollinger WD, Frasch CE, Stephens DS, Feavers I, Frosch M, Parkhill J, Vogel U, Quail MA, Bentley SD, Maiden MCJ. 2013. Description and nomenclature of Neisseria meningitidis capsule locus. Emerg. Infect. Dis. 19:566-573.
17. Dingle KE, Colles FM, Wareing DRA, Ure R, Fox AJ, Bolton FJ, Bootsma HJ, Willems RJL, Urwin R, Maiden MCJ. 2001. Multilocus sequence typing system for Campylobacter jejuni. J. Clin. Microbiol. 39:14-23.
18. Sheppard SK, Dallas JF, Strachan NJ, MacRae M, McCarthy ND, Wilson DJ, Gormley FJ, Falush D, Ogden ID, Maiden MC, Forbes KJ. 2009. Campylobacter genotyping to determine the source of human infection. Clin. Infect. Dis. 48:1072-8.
19. Sheppard SK, McCarthy ND, Falush D, Maiden MC. 2008. Convergence of Campylobacter species: implications for bacterial evolution. Science 320:237-9.
20. Cody AJ, McCarthy ND, Jansen van Rensburg M, Isinkaye T, Bentley S, Parkhill J, Dingle KE, Bowler IC, Jolley KA, Maiden MC. 2013. Real-time genomic epidemiology of human Campylobacter isolates using whole genome multilocus sequence typing. J. Clin. Microbiol. 51:2526-2534.