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Academic Staff - Associate Professor Neville Firth

Neville Firth Photo
Position: Associate Professor
Phone: +61 2 9351 3369
Fax: +61 2 9351 4771
Mobile Phone: n/a
Email: neville.firth@sydney.edu.au
Location: Room 215
Address: A12 - Macleay, The University of Sydney, NSW 2006 Australia
Links: Molecular Genetics Laboratory

Areas of Interest

The broad focus of my lab is to understand at the molecular level how bacteria are able to evolve so rapidly. In a little over half a century, strains of "golden staph" (Staphylococcus aureus) have become resistant to most useful antibiotics. As a result, this bacterial pathogen remains a major cause of hospital-acquired infections around the world, and it is increasingly a cause of serious infections in the general community. In most cases, MRSA (methicillin-resistant S. aureus) has become resistant by capturing pre-existing resistance genes and integrating them into its genome. To understand the details of how these genes are captured, regulated, inherited, and spread by S. aureus, we undertake research on the following topics:

  • Molecular biology of mobile DNA, such as multiresistance plasmids, transposons and insertion sequence (IS) elements
  • DNA replication and segregation
  • Gene transfer mechanisms such as conjugation (DNA transmission via cell-to-cell contact)
  • Regulation of gene expression

Genetic and transcriptional organisation of conjugative multiresistance plasmid pSK41 Antisense RNA control system that regulates pSK41 replication Structure of the pSK41 ParM segregation protein

Research Output

Books

  • Firth, N. & Skurray, R.A. (2006). The Staphylococcus - Genetics: Accessory elements and genetic exchange. p. 413-426. In: Fischetti, V.A., Novick, R.P., Ferretti, J.J., Portnoy, D.A., Rood, J.I. (Eds.). Gram-Positive Pathogens, 2nd Edition. American Society for Microbiology, Washington D.C.
  • Firth, N. (2003). Evolution of antimicrobial multi-resistance in Gram-positive bacteria. p. 33-60. In: Amabile-Cuevas, C.F. (Ed.). Multiple Drug Resistant Bacteria. Horizon Scientific Press, Wymondham.
  • Firth, N. & Skurray, R.A. (2000). The Staphylococcus - Genetics: Accessory elements and genetic exchange. p. 326-338. In: Fischetti, V.A., Novick, R.P., Ferretti, J.J., Portnoy, D.A., Rood, J.I. (Eds.). Gram-Positive Pathogens. American Society for Microbiology, Washington D.C.
  • Osborn, A.M., Bron, S., Firth, N., Holsappel, S., Huddleston, A., Kiewiet, R., Meijer, W., Seegers, J., Skurray, R., Terpstra, P., Thorsted, P., Tietze, E., Turner, S.L., & Thomas, C.M. (2000). The evolution of bacterial plasmids. p. 301-362. In: Thomas, C.M. (Ed.). The Horizontal Gene Pool: Bacterial Plasmids and Gene Spread. Harwood Academic, London.
  • Paulsen, I.T., Firth, N. & Skurray, R.A. (1997). Resistance to antimicrobial agents other than beta-lactams. p. 175-212. In: Crossley, K.B. &. Archer, G.L. (Eds.). The Staphylococci in Human Disease. Churchill Livingstone, New York.
  • Firth, N., Ippen-Ihler, K. & Skurray, R.A. (1996). Structure and function of the F factor and mechanism of conjugation. p. 2377-2401. In: Neidhardt, F.C., Curtiss, R., III, Ingraham, J.L., Lin, E.C.C., Low, K.B., Jr., Magasanik, B., Reznikoff, W.S., Riley, M., Schaechter, M. & Umbarger, H.E. (Eds.). Escherichia coli and Salmonella: Cellular and Molecular Biology. American Society for Microbiology, Washington D.C.

Journals

  • Howden, B.P., Seemann, T., Harrison, P.F., McEvoy C.R., Stanton, J.L., Rand, C.J., Mason, C.W., Jensen, S.O., Firth, N., Davies, J.K., Johnson, P.D.R. & Stinear, T.P. (2010). Complete genome sequence of Staphylococcus aureus strain JKD6008, a ST239 clone of methicillin-resistant Staphylococcus aureus with intermediate level vancomycin resistance. Journal of Bacteriology, in press.
  • Jensen, S.O., Apisiridej, S., Kwong, S.M., Yang, Y.H., Skurray, R.A. & Firth, N. (2010). Analysis of the prototypical Staphylococcus aureus multiresistance plasmid pSK1. Plasmid, in press.
  • Pérez-Roth, E., Kwong, S.M., Alcoba-Florez, J., Firth, N. & Méndez-Álvarez, S. (2010). Complete nucleotide sequence and comparative analysis of pPR9, a 41.7-kb conjugative staphylococcal multiresistance plasmid conferring high-level mupirocin resistance. Antimicrobial Agents and Chemotherapy. 54: 2252-2257.
  • Popp, D, Xu, W., Narita, A., Brzoska, A.J., Skurray, R.A., Firth, N., Ghoshdastider, U., Maeda, Y., Robinson, R.C. & Schumacher, M.A. (2010). Structure and filament dynamics of the pSK41 actin-like ParM protein: implications for plasmid DNA segregation. Journal of Biological Chemistry 285: 10130-10140.
  • Kwong, S.M., Jensen, S.O. & Firth, N. (2010). Prevalence of Fst-like toxin-antitoxin systems. Microbiology 156: 975-977.
  • Ni, L., Jensen, S.O., Tonthat, N.K., Berg, T, Kwong, S.M., Guan, F.H.X., Brown, M.H., Skurray, R.A., Firth, N. & Schumacher M.A. (2009). The S. aureus pSK41 plasmid encoded ArtA protein is a master regulator of plasmid transmission genes and contains a RHH motif used in alternate DNA binding modes. Nucleic Acids Research 37: 6970-6983.
  • Weaver, K.E., Kwong, S.M., Firth, N. & Francia, M.V. (2009). The RepA_N replicons of Gram-positive bacteria: a family of broadly distributed but narrow host range plasmids. Plasmid 61: 94-109.
  • Kwong, S.M., Lim, R., LeBard, R.J., Skurray, R.A. & Firth, N. (2008). Analysis of the pSK1 replicon, a prototype from the staphylococcal multiresistance plasmid family. Microbiology 154: 3084-3094.
  • Jensen, S.O., Kwong, S.M., Lyon, B.R. & Firth, N. (2008). Evolution of multiple drug resistance in staphylococci. Microbiology Australia 29 (Sept.): 120-124.
  • LeBard, R.J., Jensen, S.O., Arnaiz, I.A., Skurray, R.A. & Firth, N. (2008). A multimer resolution system contributes to segregational stability of the prototypical staphylococcal conjugative multiresistance plasmid pSK41. FEMS Microbiology Letters 284: 58-67.
  • Schumacher, M.A., Glover, T.C., Brzoska, A.J., Jensen, S.O., Dunham, T.D., Skurray, R.A. & Firth, N. (2007). Segrosome structure revealed by a complex of ParR with centromere DNA. Nature 450: 1268-1271.
  • Kwong, S.M., Skurray, R.A. & Firth, N. (2006). Replication control of staphylococcal multiresistance plasmid pSK41: an antisense RNA mediates dual-level regulation of Rep expression. Journal of Bacteriology 188: 4404-4412.
  • Kwong, S.M. & Firth, N. (2006). Regulatory RNA molecules. Microbiology Australia 27 (Sept.): 124-127.
    Kwong, S.M., Skurray, R.A. & Firth, N. (2004). Staphylococcus aureus multiresistance plasmid pSK41: Analysis of the replication region, initiator protein binding and antisense RNA regulation. Molecular Microbiology 51: 497-509.
  • Simpson, A.E., Skurray, R.A. & Firth, N. (2003). A single gene on the staphylococcal multiresistance plasmid pSK1 encodes a novel partitioning system. Journal of Bacteriology 185: 2143-2152.
  • Grkovic, S., Brown, M.H., Hardie, K. M., Firth, N. & Skurray, R.A. (2003). Stable low copy-number Staphylococcus aureus shuttle vectors. Microbiology 149: 785-794.
  • Lu, J., Manchak, J., Klimke, W., Davidson, C., Firth, N., Skurray, R.A. & Frost, L.S. (2002). Analysis and characterization of the IncFV plasmid pED208 transfer region. Plasmid 48: 24-37.
  • Simpson, A.E., Skurray, R.A. & Firth, N. (2000). An IS257-derived hybrid promoter directs transcription of a tetA(K) tetracycline resistance gene in the Staphylococcus aureus Chromosomal mec Region. Journal of Bacteriology 182: 3345-3352.
  • Firth, N., Apisiridej, S., Berg, T., O'Rourke, B.A., Curnock, S., Dyke, K.G.H. & Skurray, R.A. (2000). Replication of staphylococcal multiresistance plasmids. Journal of Bacteriology 182: 2170-2178.
  • Bayer, A.S., Prasad, R., Chandra, J., Koul, A., Smriti, M., Varma, A., Skurray, R.A., Firth, N., Brown, M.H., Koo, S.-P. & Yeaman, M.R. (2000). In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity. Infection and Immunity 68: 3548-3553.
  • Kupferwasser, L.I., Skurray, R.A., Brown, M.H., Firth, N., Yeaman, M.R. & Bayer, A.S. (1999). Plasmid-mediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: Role of the qacA locus. Antimicrobial Agents and Chemotherapy 43: 2395-2399.
  • Manwaring, N.P., Skurray, R.A. & Firth, N. (1999). Nucleotide sequence of the F plasmid leading region. Plasmid 41: 219-225.
  • Firth, N., Berg, T. & Skurray, R.A. (1999). Evolution of conjugative plasmids from Gram-positive bacteria. Molecular Microbiology 31: 1598-1599.
  • Berg, T., Firth, N., Apisiridej, S., Hettiaratchi, A., Leelaporn, A. & Skurray, R.A. (1998). Complete nucleotide sequence of pSK41: Evolution of staphylococcal conjugative multiresistance plasmids. Journal of Bacteriology 180: 4350-4359.
  • Wright, C.L., Byrne, M.E., Firth, N. & Skurray, R.A. (1998). A retrospective molecular analysis of gentamicin resistance in Staphylococcus aureus strains from UK hospitals. Journal of Medical Microbiology 47: 173-178.
  • Firth, N. & R. A. Skurray. (1998). Mobile elements in the evolution and spread of multiple-drug resistance in staphylococci. Drug Resistance Updates 1: 49-58.
  • Berg, T, Firth, N. & Skurray, R.A. (1997). Enterococcal pheromone-like activity derived from a lipoprotein signal peptide encoded by a Staphylococcus aureus plasmid. Advances in Experimental Medicine and Biology 418: 1041-1044.
  • Apisiridej, S., Leelaporn, A., Scaramuzzi, C.D., Skurray, R.A. & Firth, N. (1997). Molecular analysis of a mobilizable theta-mode trimethoprim resistance plasmid from coagulase-negative staphylococci. Plasmid 38: 13-24.
  • Skurray, R.A. & Firth, N. (1997). Molecular evolution of multiply-antibiotic-resistant staphylococci. CIBA Foundation Symposium 207: 167-191.
  • Leelaporn, A., Firth, N., Paulsen, I.T. & Skurray, R.A. (1996). IS257-mediated cointegration in the evolution of a family of staphylococcal trimethoprim resistance plasmids. Journal of Bacteriology. 178: 6070-6073.
  • Firth, N. & Skurray, R.A. (1995). A protein family associated with filament biogenesis in bacteria. Molecular Microbiology 17: 1218-1219.
  • Leelaporn, A., Firth, N., Paulsen, I.T., Hettiaratchi, A. & Skurray, R.A. (1995). Multidrug resistance plasmid pSK108 from coagulase-negative staphylococci; relationships to Staphylococcus aureus qacC plasmids. Plasmid 34: 62-67.
  • Firth, N., Fink, P.D., Johnson, L. & Skurray, R.A. (1994). A lipoprotein signal peptide encoded by the staphylococcal conjugative plasmid pSK41 exhibits an activity resembling that of Enterococcus faecalis pheromone cAD1. Journal of Bacteriology 176: 5871-5873.
  • Doran, T.J., Loh, S.M., Firth, N. & Skurray, R.A. (1994). Molecular analysis of the F plasmid traVR region: traV encodes a lipoprotein. Journal of Bacteriology 176: 4182-4186.
  • Leelaporn, A., Firth, N., Byrne, M.E., Roper, E. and Skurray, R.A. (1994). Possible role of insertion sequence IS257 in dissemination and expression of high- and low-level trimethoprim resistance in staphylococci. Antimicrobial Agents and Chemotherapy 38: 2238-2244.
  • Firth, N., Ridgway, K.P, Byrne, M.E., Fink, P.D., Johnson, L., Paulsen, I.T. & Skurray, R.A. (1993). Analysis of a transfer region from the staphylococcal conjugative plasmid pSK41. Gene 136: 13-25.
  • Firth, N. & Skurray, R. (1992). Characterization of the F plasmid bifunctional conjugation gene, traG. Molecular and General Genetics 232: 145-153.
  • Ham, L.M., Firth, N. & Skurray, R. (1989). Nucleotide sequence of the F plasmid transfer gene, traH: identification of a new gene and promoter within the transfer operon. Gene 75: 157-165.