Methicillin-resistant Staphylococcus aureus (MRSA) are a leading cause of infectious disease in the United States and elsewhere in the world;these bacteria have acquired resistance to all relevant classes of antibiotics and have become established in community and healthcare environments. Staphylococcus epidermidis and other coagulase-negative staphylococci, once exclusively considered to be commensal species, have emerged as a leading cause of infections associated with indwelling medical devices. Much of the human morbidity and mortality caused by staphylococci are due to a small number of successful, widespread clones. In the current proposal, we seek to exploit the power of rapid next-generation sequencing to obtain a more complete perspective of clone emergence and adaptation for several pathogenic staphylococci. Specifically, we will (1) elucidate fine-scale population structure and the origins, patterns of geographic spread, and evolution of clinically important traits of the USA300 MRSA clone, to characterize an ongoing epidemic, identify biomarkers of key variants, and provide baseline data for future epidemiological interventions;(2) validate coarse-scale population structure within pathogenic coagulase-negative species to identify novel biomarkers of pathogenic variants;(3) compare genome-wide targets of long-term positive selection in S. aureus and S. epidermidis and reveal the importance of balanced polymorphisms to specific antimicrobial resistances.
Staphylococcus bacteria include established and emerging human pathogens. This proposal will analyze the DNA of some of the most pathogenic staphylococci, in order to reveal how strains emerge as pathogens and adapt to their human hosts. New molecular and analytical tools for identifying and tracking these strains will be generated, and new targets of potential diagnostic and therapeutic interest will be identified.
|Thomas, Jonathan C; Zhang, Liangfen; Robinson, D Ashley (2014) Differing lifestyles of Staphylococcus epidermidis as revealed through Bayesian clustering of multilocus sequence types. Infect Genet Evol 22:257-64|
|Zhang, Liangfen; Thomas, Jonathan C; Miragaia, Maria et al. (2013) Multilocus sequence typing and further genetic characterization of the enigmatic pathogen, Staphylococcus hominis. PLoS One 8:e66496|
|Thomas, Jonathan C; Godfrey, Paul A; Feldgarden, Michael et al. (2012) Draft genome sequences of Staphylococcus aureus sequence type 34 (ST34) and ST42 hybrids. J Bacteriol 194:2740-1|
|Lattar, S M; Tuchscherr, L P N; Centron, D et al. (2012) Molecular fingerprinting of Staphylococcus aureus isolated from patients with osteomyelitis in Argentina and clonal distribution of the cap5(8) genes and of other selected virulence genes. Eur J Clin Microbiol Infect Dis 31:2559-66|
|Price, Lance B; Stegger, Marc; Hasman, Henrik et al. (2012) Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. MBio 3:|
|Thomas, Jonathan C; Godfrey, Paul A; Feldgarden, Michael et al. (2012) Candidate targets of balancing selection in the genome of Staphylococcus aureus. Mol Biol Evol 29:1175-86|
|Smyth, Davida S; Wong, Agnes; Robinson, D Ashley (2011) Cross-species spread of SCCmec IV subtypes in staphylococci. Infect Genet Evol 11:446-53|
|Severiano, Ana; Carrico, Joao A; Robinson, D Ashley et al. (2011) Evaluation of jackknife and bootstrap for defining confidence intervals for pairwise agreement measures. PLoS One 6:e19539|
|Wong, Agnes; Reddy, Shilpa P; Smyth, Davida S et al. (2010) Polyphyletic emergence of linezolid-resistant staphylococci in the United States. Antimicrob Agents Chemother 54:742-8|
|Chen, Liang; Mediavilla, Jose R; Smyth, Davida S et al. (2010) Identification of a novel transposon (Tn6072) and a truncated staphylococcal cassette chromosome mec element in methicillin-resistant Staphylococcus aureus ST239. Antimicrob Agents Chemother 54:3347-54|
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