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研究领域

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

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Ramsay, J., Kwong, S., Murphy, R., Eto, K., Price, K., Nguyen, Q., O’Brien, F., Grubb, W., Coombs, G., Firth, N. (2016). An updated view of plasmid conjugation and mobilization in Staphylococcus. Mobile Genetic Elements, 6(4), e1208317. [More Information] Brzoska, A., Jensen, S., Barton, D., Davies, D., Overall, R., Skurray, R., Firth, N. (2016). Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein. PloS One, 11(6), e0156944. [More Information] Pollet, R., Ingle, J., Hymes, J., Eakes, T., Eto, K., Kwong, S., Ramsay, J., Firth, N., Redinbo, M. (2016). Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci. Journal of Bacteriology, 198(6), 888-897. [More Information] Baines, S., Holt, K., Schultz, M., Seemann, T., Howden, B., Jensen, S., van Hal, S., Coombs, G., Firth, N., Powell, D., et al (2015). Convergent adaptation in the dominant global hospital clone ST239 of methicillin-resistant Staphylococcus aureus. MBIO, 6(2), 1-9. [More Information] Kwong, S., Firth, N. (2015). Structural and sequence requirements for the antisense RNA regulating replication of staphylococcal multiresistance plasmid pSK41. Plasmid, 78, 17-25. [More Information] Schumacher, M., Tonthat, N., Kwong, S., Chinnam, N., Liu, M., Skurray, R., Firth, N. (2014). Mechanism of staphylococcal multiresistance plasmid replication origin assembly by the RepA protein. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 111(25), 9121-9126. [More Information] Abtin, A., Jain, R., Mitchell, A., Roediger, B., Brzoska, A., Tikoo, S., Cheng, Q., Ng, L., Cavanagh, L., von Andrian, U., Firth, N., et al (2014). Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nature Immunology, 15(1), 45-53. [More Information] Solis, N., Parker, B., Kwong, S., Robinson, G., Firth, N., Cordwell, S. (2014). Staphylococcus aureus Surface Proteins Involved in Adaptation to Oxacillin Identified Using a Novel Cell Shaving Approach. Journal of Proteome Research, 13(6), 2954-2972. [More Information] Liu, M., Kwong, S., Jensen, S., Brzoska, A., Firth, N. (2013). Biology of the staphylococcal conjugative multiresistance plasmid pSK41. Plasmid, 70(1), 42-51. [More Information] Edwards, J., Betts, L., Frazier, M., Pollet, R., Kwong, S., Walton, W., Ballentine, K., Huang, J., Habibi, S., Campo, M., Firth, N., et al (2013). Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 110(8), 2804-2809. [More Information] Brzoska, A., Firth, N. (2013). Two-Plasmid Vector System for Independently Controlled Expression of Green and Red Fluorescent Fusion Proteins in Staphylococcus aureus. Applied and Environmental Microbiology, 79(9), 3133-3136. [More Information] Liu, M., Kwong, S., Pon, C., Skurray, R., Firth, N. (2012). Genetic requirements for replication initiation of the staphylococcal multiresistance plasmid pSK41. Microbiology, 158(6), 1456-1467. [More Information] Liew, A., Theis, T., Jensen, S., Garcia-Lara, J., Foster, S., Firth, N., Lewis, P., Harry, E. (2011). A simple plasmid-based system that allows rapid generation of tightly controlled gene expression in Staphylococcus aureus. Microbiology, 157(3), 666-676. [More Information] Shearer, J., Wireman, J., Hostetler, J., Forberger, H., Borman, J., Gill, J., Sanchez, S., Mankin, A., LaMarre, J., Lindsay, J., Jensen, S., Firth, N., Skurray, R., et al (2011). Major families of multiresistant plasmids from geographically and epidemiologically diverse staphylococci. G3: Genes, Genomes, Genetics, 1, 581-591. [More Information] Jensen, S., Apisiridej, S., Kwong, S., Yang, J., Skurray, R., Firth, N. (2010). Analysis of the prototypical Staphylococcus aureus multiresistance plasmid pSK1. Plasmid, 64(3), 135-142. [More Information] Howden, B., Seemann, T., Harrison, P., McEvoy, C., Stanton, J., Rand, C., Mason, C., Jensen, S., Firth, N., Davies, J., et al (2010). Complete Genome Sequence of Staphylococcus aureus Strain JKD6008, an ST239 Clone of Methicillin-Resistant Staphylococcus Aureus with Intermediate-Level Vancomycin Resistance. Journal of Bacteriology, 192(21), 5848-5849. [More Information] Perez-Roth, E., Kwong, S., Alcoba-Florez, J., Firth, N., Mendez-Alvarez, S. (2010). Complete Nucleotide Sequence and Comparative Analysis of pPR9, a 41.7-Kilobase Conjugative Staphylococcal Multiresistance Plasmid Conferring High-Level Mupirocin Resistance. Antimicrobial Agents and Chemotherapy, 54(5), 2252-2257. [More Information] Kwong, S., Jensen, S., Firth, N. (2010). Prevalence of Fst-like toxin–antitoxin systems. Microbiology, 156(4), 975-977. [More Information] Popp, D., Xu, W., Narita, A., Brzoska, A., Skurray, R., Firth, N., Goshdastider, U., Maeda, Y., Robinson, R., Schumacher, M. (2010). Structure and Filament Dynamics of the pSK41 Actin-like ParM Protein Implications for Plasmid DNA Segregation. Journal of Biological Chemistry, 285(13), 10130-10140. [More Information] Weaver, K., Kwong, S., Firth, N., Francia, M. (2009). The RepA_N replicons of Gram-positive bacteria: a family of broadly distributed but narrow host range plasmids. Plasmid, 61(2), 94-109. [More Information]

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