User:Timothy P. Stinear

• Tim Stinear
• Department of Microbiology and Immunology
• University of Melbourne
• Royal Parade
• Parkville, Victoria, Australia.
• Email me at: tstinear@unimelb.edu.au

Education

• 2001, PhD, Monash University
• 1995, BSc (Hons), Monash University
• 1989, BSc, Monash University

Research interests

1. Mycobacterium ulcerans
2. Biosynthesis of mycolactones
3. Staphylococcus aureus

Recent Publications

1. Porter JL, Tobias NJ, Hong H, Tuck KL, Jenkin GA, and Stinear TP. Transfer, stable maintenance and expression of the mycolactone polyketide megasynthase mls genes in a recombination-impaired Mycobacterium marinum. Microbiology (Reading). 2009 Jun;155(Pt 6):1923-1933. DOI:10.1099/mic.0.027029-0 |

   This article describes our transfer of the pMUM001 plasmid from M. ulcerans Agy99 to M. marinumM with the aim of creating a tractable mycobacterium for detailed studies of mycolactone biosynthesis. Unfortunately M. marinumM + pMUM001 does not equal mycolactone-producing mycobacterium as one might have expected.

2. Pidot SJ, Hong H, Seemann T, Porter JL, Yip MJ, Men A, Johnson M, Wilson P, Davies JK, Leadlay PF, and Stinear TP. Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones. BMC Genomics. 2008 Oct 7;9:462. DOI:10.1186/1471-2164-9-462 |
3. Lavender CJ, Stinear TP, Johnson PD, Azuolas J, Benbow ME, Wallace JR, and Fyfe JA. Evaluation of VNTR typing for the identification of Mycobacterium ulcerans in environmental samples from Victoria, Australia. FEMS Microbiol Lett. 2008 Oct;287(2):250-5. DOI:10.1111/j.1574-6968.2008.01328.x |
4. Howden BP, Stinear TP, Allen DL, Johnson PD, Ward PB, and Davies JK. Genomic analysis reveals a point mutation in the two-component sensor gene graS that leads to intermediate vancomycin resistance in clinical Staphylococcus aureus. Antimicrob Agents Chemother. 2008 Oct;52(10):3755-62. DOI:10.1128/AAC.01613-07 |

   This article describes the application of comparative genomics to identify a point mutation in a regulatory gene that confers increased resistance to vancomycin on methicillin resistant Staphylococcus aureus

5. Stragier P, Hermans K, Stinear T, and Portaels F. First report of a mycolactone-producing Mycobacterium infection in fish agriculture in Belgium. FEMS Microbiol Lett. 2008 Sep;286(1):93-5. DOI:10.1111/j.1574-6968.2008.01264.x |
6. Tafelmeyer P, Laurent C, Lenormand P, Rousselle JC, Marsollier L, Reysset G, Zhang R, Sickmann A, Stinear TP, Namane A, and Cole ST. Comprehensive proteome analysis of Mycobacterium ulcerans and quantitative comparison of mycolactone biosynthesis. Proteomics. 2008 Aug;8(15):3124-38. DOI:10.1002/pmic.200701018 |
7. Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C, Clarke K, Cronin A, Davis P, Goodhead I, Holroyd N, Jagels K, Lord A, Moule S, Mungall K, Norbertczak H, Quail MA, Rabbinowitsch E, Walker D, White B, Whitehead S, Small PL, Brosch R, Ramakrishnan L, Fischbach MA, Parkhill J, and Cole ST. Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 2008 May;18(5):729-41. DOI:10.1101/gr.075069.107 |
8. Stinear T and Johnson PD. First isolation of Mycobacterium ulcerans from an aquatic environment: the end of a 60-year search?. PLoS Negl Trop Dis. 2008 Mar 26;2(3):e216. DOI:10.1371/journal.pntd.0000216 |

   A commentary on the first isolation of Mycobacterium ulcerans from an insect by the research team of Professor Françoise Portaels

9. Howden BP, Smith DJ, Mansell A, Johnson PD, Ward PB, Stinear TP, and Davies JK. Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia. BMC Microbiol. 2008 Feb 27;8:39. DOI:10.1186/1471-2180-8-39 |
10. Johnson PD, Azuolas J, Lavender CJ, Wishart E, Stinear TP, Hayman JA, Brown L, Jenkin GA, and Fyfe JA. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. 2007 Nov;13(11):1653-60. DOI:10.3201/eid1311.061369 |
11. Rondini S, Käser M, Stinear T, Tessier M, Mangold C, Dernick G, Naegeli M, Portaels F, Certa U, and Pluschke G. Ongoing genome reduction in Mycobacterium ulcerans. Emerg Infect Dis. 2007 Jul;13(7):1008-15. DOI:10.3201/eid1307.060205 |
12. Hong H, Stinear T, Porter J, Demangel C, and Leadlay PF. A novel mycolactone toxin obtained by biosynthetic engineering. Chembiochem. 2007 Nov 23;8(17):2043-7. DOI:10.1002/cbic.200700411 |
13. Käser M, Rondini S, Naegeli M, Stinear T, Portaels F, Certa U, and Pluschke G. Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans. BMC Evol Biol. 2007 Sep 27;7:177. DOI:10.1186/1471-2148-7-177 |
14. Fyfe JA, Lavender CJ, Johnson PD, Globan M, Sievers A, Azuolas J, and Stinear TP. Development and application of two multiplex real-time PCR assays for the detection of Mycobacterium ulcerans in clinical and environmental samples. Appl Environ Microbiol. 2007 Aug;73(15):4733-40. DOI:10.1128/AEM.02971-06 |
15. Hilty M, Käser M, Zinsstag J, Stinear T, and Pluschke G. Analysis of the Mycobacterium ulcerans genome sequence reveals new loci for variable number tandem repeats (VNTR) typing. Microbiology (Reading). 2007 May;153(Pt 5):1483-1487. DOI:10.1099/mic.0.2006/004564-0 |
16. Lavender CJ, Senanayake SN, Fyfe JA, Buntine JA, Globan M, Stinear TP, Hayman JA, and Johnson PD. First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer) acquired in New South Wales. Med J Aust. 2007 Jan 15;186(2):62-3. DOI:10.5694/j.1326-5377.2007.tb00801.x |
17. Stinear TP, Seemann T, Pidot S, Frigui W, Reysset G, Garnier T, Meurice G, Simon D, Bouchier C, Ma L, Tichit M, Porter JL, Ryan J, Johnson PD, Davies JK, Jenkin GA, Small PL, Jones LM, Tekaia F, Laval F, Daffé M, Parkhill J, and Cole ST. Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome Res. 2007 Feb;17(2):192-200. DOI:10.1101/gr.5942807 |
18. Yip MJ, Porter JL, Fyfe JA, Lavender CJ, Portaels F, Rhodes M, Kator H, Colorni A, Jenkin GA, and Stinear T. Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria from a common Mycobacterium marinum progenitor. J Bacteriol. 2007 Mar;189(5):2021-9. DOI:10.1128/JB.01442-06 |
19. Howden BP, Johnson PD, Ward PB, Stinear TP, and Davies JK. Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2006 Sep;50(9):3039-47. DOI:10.1128/AAC.00422-06 |
20. Hong H, Stinear T, Skelton P, Spencer JB, and Leadlay PF. Structure elucidation of a novel family of mycolactone toxins from the frog pathogen Mycobacterium sp. MU128FXT by mass spectrometry. Chem Commun (Camb). 2005 Sep 14(34):4306-8. DOI:10.1039/b506835e |
21. Stinear TP, Pryor MJ, Porter JL, and Cole ST. Functional analysis and annotation of the virulence plasmid pMUM001 from Mycobacterium ulcerans. Microbiology (Reading). 2005 Mar;151(Pt 3):683-692. DOI:10.1099/mic.0.27674-0 |
22. Hong H, Spencer JB, Porter JL, Leadlay PF, and Stinear T. A novel mycolactone from a clinical isolate of Mycobacterium ulcerans provides evidence for additional toxin heterogeneity as a result of specific changes in the modular polyketide synthase. Chembiochem. 2005 Apr;6(4):643-8. DOI:10.1002/cbic.200400339 |
23. Stinear TP, Hong H, Frigui W, Pryor MJ, Brosch R, Garnier T, Leadlay PF, and Cole ST. Common evolutionary origin for the unstable virulence plasmid pMUM found in geographically diverse strains of Mycobacterium ulcerans. J Bacteriol. 2005 Mar;187(5):1668-76. DOI:10.1128/JB.187.5.1668-1676.2005 |
24. Marsollier L, Stinear T, Aubry J, Saint André JP, Robert R, Legras P, Manceau AL, Audrain C, Bourdon S, Kouakou H, and Carbonnelle B. Aquatic plants stimulate the growth of and biofilm formation by Mycobacterium ulcerans in axenic culture and harbor these bacteria in the environment. Appl Environ Microbiol. 2004 Feb;70(2):1097-103. DOI:10.1128/AEM.70.2.1097-1103.2004 |
25. Stinear TP, Mve-Obiang A, Small PL, Frigui W, Pryor MJ, Brosch R, Jenkin GA, Johnson PD, Davies JK, Lee RE, Adusumilli S, Garnier T, Haydock SF, Leadlay PF, and Cole ST. Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1345-9. DOI:10.1073/pnas.0305877101 |

    Discovery of the pMUM001 plasmid in Mycobacterium ulcerans Agy99

26. Gordon SV, Bottai D, Simeone R, Stinear TP, and Brosch R. Pathogenicity in the tubercle bacillus: molecular and evolutionary determinants. Bioessays. 2009 Apr;31(4):378-88. DOI:10.1002/bies.200800191 |
27. Demangel C, Stinear TP, and Cole ST. Buruli ulcer: reductive evolution enhances pathogenicity of Mycobacterium ulcerans. Nat Rev Microbiol. 2009 Jan;7(1):50-60. DOI:10.1038/nrmicro2077 |
28. Hong H, Demangel C, Pidot SJ, Leadlay PF, and Stinear T. Mycolactones: immunosuppressive and cytotoxic polyketides produced by aquatic mycobacteria. Nat Prod Rep. 2008 Jun;25(3):447-54. DOI:10.1039/b803101k |
29. Johnson PD, Stinear T, Small PL, Pluschke G, Merritt RW, Portaels F, Huygen K, Hayman JA, and Asiedu K. Buruli ulcer (M. ulcerans infection): new insights, new hope for disease control. PLoS Med. 2005 Apr;2(4):e108. DOI:10.1371/journal.pmed.0020108 |
30. ISBN:0879697164

Useful links

• Stinear Laboratory
• BuruList: Access the M. ulcerans genome
• Introductory tutorial
• OpenWetWare help pages