Laboratory of Human Bacterial Pathogenesis

Emergent Bacterial Pathogens Section

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James Musser, M.D., Ph.D.

Chief, Laboratory of Human Bacterial Pathogenesis
E-mail: jmusser@niaid.nih.gov

Dr. Musser received his M.D. and Ph.D. from the University of Rochester School of Medicine. Following postdoctoral research at the Institute of Molecular Evolutionary Genetics, Pennsylvania State University, and residency training in laboratory medicine at the Hospital of the University of Pennsylvania, he joined the Department of Pathology, Baylor College of Medicine, Houston, Texas. He advanced through the academic ranks from 1991 to 1998, when he was promoted to Professor. Dr. Musser joined NIAID in 1999 as Chief, Laboratory of Human Bacterial Pathogenesis. His research focuses on the molecular basis of host-pathogen interactions in group A Streptococcus and Mycobacterium tuberculosis. He serves on several editorial boards and has received many national and international honors and awards.

Description of Research

The long-term goals of research conducted in the laboratory are to understand the molecular basis of diseases caused by the human pathogenic bacterium Group A Streptococcus (GAS) and elucidate the molecular basis underlying variation in the character of disease caused by Mycobacterium tuberculosis. Genome-scale and high-throughput strategies are used to investigate: (1) the role of extracellular GAS proteins in host-pathogen interactions (2) potential immunoprophylaxis applications of these proteins (3) the molecular pathogenesis of rheumatic fever and rheumatic heart disease. In M. tuberculosis, the laboratory is addressing: (1) the molecular genetic basis of antimicrobial agent resistance (2) the genetics of disease specificity recently identified for certain M. tuberculosis clones and (3) the human genetics of susceptibility to this pathogen. To address these issues, a highly integrated approach is used that encompasses bacterial molecular genetics, genome sequencing, molecular population genetic analysis, and human genetic epidemiology.

Major Areas of Research Group A Streptococcus Mycobacterium tuberculosis

Selected Recent Publications

Banks D.J, Beres S.B and Musser J.M. The fundamental contribution of phages to group A Streptococcus evolution, genome diversification and strain emergence. Trends Microbiol. 10:515-521, 2002.

Smoot J.C, Barbian K.D, Van Gompel J.J, Smoot L.M, Chaussee M.S, Sylva G.L, Sturdevant D.E, Ricklefs S.M, Porcella S.F, Parkins L.D, Beres S.B, Campbell D.S, Smith T.M, Zhang Q, Kapur V, Daly J.A, Veasy L.G, Musser J.M. Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci.USA 99 (7):4668-73, 2002.

Hoe N.P, Ireland R.M, DeLeo F.R, Gowen B.B, Dorward D.W, Voyich J.M, Liu M, Burns E.H Jr, Culnan D.M, Bretscher A, Musser J.M. Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells. Proc. Natl. Acad. Sci. USA 99 (11):7646-51, 2002.

Beres S.B, Sylva G.L, Barbian K.D, Lei B, Hoff J.S, Mammarella N.D, Liu M.Y, Smoot J.C, Porcella S.F, Parkins L.D, Campbell D.S, Smith T.M, McCormick J.K, Leung D.Y, Schlievert P.M, Musser J.M. Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc. Natl. Acad. Sci. USA 99 (15):10078-83, 2002.

Graham M.R, Smoot L.M, Migliaccio C.A, Virtaneva K, Sturdevant D.E, Porcella S.F, Federle M.J, Adams G.J, Scott J.R, Musser J.M. Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Proc. Natl. Acad. Sci. USA 99 (21):13855-60, 2002.

Gutacker M.M, Smoot J.C, Migliaccio C.A, Ricklefs S.M, Hua S, Cousins D.V, Graviss E.A, Shashkina E, Kreiswirth B.N, Musser J.M. Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms. Resolution of genetic relationships among closely related microbial strains. Genetics 162(4):1533-43, 2002.