Ph.D. (1994) |
Martin
S. Pavelka, Jr.
Associate Professor of Microbiology & Immunology Primary Appointment: GEBS Cluster Affiliations: |
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| Contact Information: | ||
| University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Phone:
(585) 275-4670 E-Mail: martin_pavelka@ urmc.rochester.edu |
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- Research Focus
- Cell envelopes of pathogenic bacteria
- Research Overview
- Our laboratory is interested in the genetics and biochemistry of the cell envelopes of pathogenic bacteria. We are also interested in studying how components of the cell envelope contribute to the pathogenesis of bacterial diseases. We currently focus on the diseases tuberculosis and tularemia.
- Tuberculosis, caused by the atypical Gram-positive organism Mycobacterium tuberculosis, kills more adults than any other single organism. Key features of M. tuberculosis include its complex cell envelope and its ability to persist in a latent state in infected individuals. The mycobacterial cell envelope is an asymmetric bilayer, with an outer layer composed of glycolipids, and an inner layer composed of mycolic acids covalently attached to an arabinogalactan polysaccharide. The arabinogalactan is in turn covalently attached to the peptidoglycan via a unique disaccharide linkage, forming the mycolylarabinogalactan-peptidoglycan complex (mAGP). The major focus of the lab's research on mycobacterial cell envelopes is the biosynthesis of the peptidoglycan component. Peptidoglycan (PGN) is an essential component of the bacterial cell envelope, providing both shape and structural integrity to the cell. PGN fragments are also important in the recognition of bacterial pathogens by the innate immune system. Mycobacterial PGN consists of glycan chains composed of N-glycolylmuramic acid and N-acetylglucosamine with crosslinked tetrapeptides (L-alanyl-D-iso -glutaminyl-meso-diaminopimelyl-D- alanine) attached to the muramic acid moieties. Peptide cross-links occur between meso-diaminopimelic acid (DAP) residues and either D-alanine or other DAP residues. The mycobacterial PGN is notable in that it has N-glycolylated muramic acid and is highly cross-linked, with 70-80% of the peptides cross-linked and one-third to one-half of the cross-links represented by the unusual DAP-DAP variety. Our laboratory is studying the biological significance of the N-glycolylmuramic acid and the DAP-DAP linkages with the hope of discovering new pathways to exploit for the development of new anti-tuberculosis drugs.
- Tularemia is a zoonotic disease caused by the Gram-negative bacterium Francisella tularensis. This organism is considered a potentially dangerous biological weapon because of its extreme infectivity via the aerosol route and the severity of the human disease it causes. The fastidious nature of the bacterium, the requirement that it be handled using biosafety level three (BSL3) containment, and the paucity of genetic tools have hindered research on this organism. Thus, compared to other pathogens, little is known about F. tularensis physiology, genetics, and pathogenesis. Our laboratory has developed new genetic tools for the manipulation of highly virulent F. tularensis subsp. tularensis. Currently, we are refining these tools and using them to understand the biology of the cell envelope in this organism, chiefly examining secreted proteins and the roles they play in envelope physiology and tularemia pathogenesis.
- Recent Publications
- Pavelka MS Allelic exchange of unmarked mutations in mycobacterium tuberculosis. Methods Mol Biol. 2008;435:191-201
- D'Angio CT, Boohene PA, Mowrer A, Audet S, Menegus MA, Schmid DS, Beeler JA.
"Measles-mumps-rubella and varicella vaccine responses in extremely preterm infants." Pediatrics. 2007 Mar;119(3):e574-9. - Lovullo ED, Sherrill LA, Perez LL, Pavelka MS "Genetic tools for highly pathogenic Francisella tularensis subsp. tularensis." Microbiology. 2006 Nov;152(Pt 11):3425-35
- Flores AR, Parsons LM, Pavelka MS Jr. "Characterization of novel Mycobacterium tuberculosis and Mycobacterium smegmatis mutants hypersusceptible to beta-lactam antibiotics." J Bacteriol. 2005 Mar;187(6):1892-900.
- Consaul, S. A, Wright, L. F, Mahapatra, S, Crick, D. C, Pavelka, M. S., Jr. "An unusual mutation results in the replacement of diaminopimelate with lanthionine in the peptidoglycan of a mutant strain of Mycobacterium smegmatis." J Bacteriol 187(5): 1612-20, 2005.
- Flores, A. R, Parsons, L. M, Pavelka, M. S., Jr.. "Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics." Microbiology 151(Pt 2): 521-32, 2005.
- Raymond, J. B, Mahapatra, S. Crick, D. C, Pavelka, M. S., Jr. "Identification of the namH gene, encoding the hydroxylase responsible for the N-glycolylation of the mycobacterial peptidoglycan." J Biol Chem 280(1): 326-33, 2005.
- Consaul SA, Pavelka MS Jr. Use of a novel allele of the Escherichia coli aacC4 aminoglycoside resistance gene as a genetic marker in mycobacteria. FEMS Microbiol Lett. 234:297-301, 2004.
- Raymond JB, Price NP, Pavelka MS Jr. A method for the enzymatic synthesis and HPLC purification of the peptidoglycan precursor UDP-N-acetylmuramic acid. FEMS Microbiol Lett. 229:83-9, 2003.
- Consaul SA, Jacobs WR Jr, Pavelka MS Jr. Extragenic suppression of the requirement for diaminopimelate in diaminopimelate auxotrophs of Mycobacterium smegmatis. FEMS Microbiol Lett. 225:131-5, 2003.
- Pavelka MS Jr, Chen B, Kelley CL, Collins FM, Jacobs Jr WR Jr. Vaccine efficacy of a lysine auxotroph of Mycobacterium tuberculosis. Infect Immun. 71:4190-2, 2003.
- Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC. Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis. J Biol Chem. 278:18588-96, 2003.
- Pavelka MS Jr, Jacobs WR Jr. Comparison of the construction of unmarked deletion mutations in Mycobacterium smegmatis, Mycobacterium bovis bacillus Calmette-Guerin, and Mycobacterium tuberculosis H37Rv by allelic exchange. J Bacteriol 181:4780-9, 1999.
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