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David Popham

popham
207 Life Sciences I Building (MC 0910)
970 Washington Street NW
Blacksburg, VA 24061

The Popham Lab Website

Major Field of Interest

Molecular Microbiology

B.S. Washington University in St. Louis (1983)
Ph.D. University of California-Davis (1989)
Postdocs:
Institut de Biologie Physico-Chimique, Paris (1989-1991)
University of Connecticut Health Center (1991-1996)

Bacillus subtilis Projects
Polymerization of the bacterial peptidoglycan cell wall has proven to be one of the best targets for antibiotics because it is essential for the cells, is highly conserved across essentially all bacterial genera, and takes place outside of the cell, where the antibiotics have easy access. A greater understanding of the details of peptidoglycan polymerization will contribute to the development of new antibiotics. With funding from a grant from the NIH, we study many aspects of peptidoglycan synthesis in B. subtilis. These include: 1) The roles played by the 16 different penicillin-binding proteins (PBPs) in putting together vegetative cell walls and spore cell walls of the proper shape, size and structure; 2) The protein-protein interactions made by the major PBPs; 3) Regulation of the timing of spore peptidoglycan synthesis; and 4) The relationship of spore peptidoglycan structure and spore resistance properties.

Bacillus anthracis Projects
The spores that cause Anthrax can lie in a dormant, extremely stable state for many years. In addition, these spores are highly resistant to most treatments commonly used for disinfection. Once the spores enter a host body, they must germinate and return to a growing state in order to cause disease. This germination also renders the spores sensitive to disinfection agents. With funding from a grant from the NIH, we are determining the enzymatic activities required for degradation of the B. anthracis spore peptidoglycan wall, an essential step in spore germination. With an understanding of the proteins involved in germination and the mechanism that triggers this process, we may be able to design ways to either prevent or stimulate germination. This can lead to better methods of infection control and cleanup of contaminated sites.

Clostridium difficile Project
The bacterium C. difficile has become one of the most serious human bacterial pathogens in the United States, especially among hospitalized patients that have undergone aggressive antibiotic treatment for a prior condition. C. difficile's ability to produce a heat-resistant endospore is the most important factor in allowing it to spread between patients, to persist in clinical settings, and to cause frequent relapses in patients. With funding from the NIH, and in collaboration with Drs. Rich Helm, Rick Jensen, and Stephen Melville, and the VT Mass Spectrometry Incubator, we will identify proteins within the inner membrane of C. difficile spores, with the goal of better understanding the spore germination process. With this information, we may be able to design ways to either prevent or stimulate germination. This can lead to better methods of infection control and cleanup of contaminated sites.

 

 

 

  • Jing, X., H.R. Robinson, J.D. Heffron, D.L. Popham, and F.D. Schubot (2012) The catalytic domain of the germination-specific lytic transglycosylase SleB from Bacillus anthracis displays a unique active site topology. Proteins. 80:2469-2475.Abstract
  • Popham, D. L., J. D. Heffron, and E. A. Lambert. (2012) Degradation of Spore Peptidoglycan During Germination. In: Bacterial Spores: Current Research and Applications. Ernesto Abel-Santos (ed.) Caister Academic Press, Norwich, UK.Abstract
  • Lambert, E. A., N. Sherry, and D. L. Popham. (2012) In vitro and in vivo analyses of the Bacillus anthracis SleL protein. Microbiology. 158:1359-1368.Abstract
  • Volokhov, D. V., M. Amselle, B. J. Beck, D. L. Popham, P. Whittaker, H. Wang, E. Kerrigan, V. E. Chizhikov. (2011) Lactobacillus brantae sp. nov., isolated from feces of Canada geese (Branta canadensis). Intl. J. Syst. Evol. Microbiol. Oct Epub.Abstract
  • Hachmann, A.-B., E. Sevim, A. Gaballa, D. L. Popham, H. Antelmann, and J. D. Helmann. (2011) Reduction in membrane phosphatidylglycerol content leads to daptomycin resistance in Bacillus subtilis. Antimicrob. Agents Chemother. 55:4326-4337.Abstract
  • Heffron, J., N. Sherry, and D. L. Popham. (2011) In vitro studies of peptidoglycan binding and hydrolysis by the Bacillus anthracis germination-specific lytic enzyme SleB. J. Bacteriol. 193:125-131.Abstract
  • Heffron, J., E. A. Lambert, N. Sherry, and D. L. Popham. (2010). Contributions of four cortex lytic enzymes to germination of Bacillus anthracis spores. J. Bacteriol. 192: 763-770.Abstract
  • Orsburn, B., S. B. Melville, and D. L. Popham. (2010) EtfA catalyzes the formation of dipicolinic acid in Clostridium perfringens. Mol. Microbiol. 75:178-186.Abstract
  • Arends, S. J. R., K. Williams, R. J. Scott, S. Rolong, D. L. Popham, and D. S. Weiss. (2010) Discovery and characterization of three new Escherichia coli septal ring proteins that contain a SPOR domain: DamX, DedD, and RlpA. J. Bacteriol. 192:242-245.Abstract
  • Vasudevan, P., J. McElligott, C. Attkisson, M. Betteken, and D. L. Popham (2009) Homologues of the Bacillus subtilis SpoVB protein are involved in cell wall metabolism. J. Bacteriol. 191:6012-6019.Abstract
  • Cohen, D. N., Y. Y. Sham, G. D. Haugstad, Y. Xiang, M. G. Rossmann, D. L. Anderson, and D. L. Popham. (2009). Shared catalysis in virus entry and bacterial cell wall depolymerization. J. Mol Biol. 387: 607-618.Abstract
  • Heffron, J., B. Orsburn, and D. L. Popham. (2009). The roles of germination-specific lytic enzymes CwlJ and SleB in Bacillus anthracis . J. Bacteriol. 191: 2237-2247.Abstract
  • Orsburn, B., K. Sucre, D. L. Popham, and S. B. Melville. (2009). The SpmA/B and DacF proteins of Clostridium perfringens play important roles in spore heat resistance. FEMS Microbiol Lett. 291:188-194.Abstract
  • Lambert, E. and D. L. Popham. (2008). The Bacillus anthracis SleL (YaaH) protein is an N-acetylglucosaminidase involved in spore cortex depolymerization. J. Bacteriol. 190:7601-7607.
  • Shah, I. M., M. H. Laaberki, D. L. Popham, and J. Dworkin. (2008). A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments. Cell 135:486-96.Abstract
  • Dowd, M. M., B. Orsburn, and D. L. Popham. (2008). Cortex peptidoglycan lytic activity in germinating Bacillus anthracis spores. J. Bacteriol. 190:4541-4548.Abstract
  • Suklim K., G. J. Flick, D. W. Bourne, L. A. Granata, J. Eifert, R. Williams, D. Popham, R. Wittman. (2008). Pressure-induced germination and inactivation of Bacillus cereus spores and their survival in fresh blue crab meat (Callinectes sapidus) during storage. J. Aquatic Food Product Tech. 17:322-337.Abstract
  • Suklim K., G. J. Flick, D. W. Bourne, L. A. Granata, J. Eifert, R. Williams, D. Popham, R. Wittman. (2008). Microbiology, physical and sensory quality of vacuum-packaged fresh blue crab meat (Callinectes sapidus) treated with high hydrostatic pressure. Food Protection Trends. 28:96-106.Abstract
  • Orsburn, B., S. B. Melville, and D. L. Popham. Factors contributing to heat resistance of Clostridium perfringens endospores. Appl. Environ. Microbiol. 74:3328-3335. 2008Abstract
  • Vasudevan, P., A. Weaver, E. D. Reichert, S. D. Linnstaedt, and D. L. Popham. Spore cortex formation in Bacillus subtilis is regulated by accumulation of peptidoglycan precursors under control of sigma K. Molec. Microbiol. 65:1582-1594. 2007Abstract
  • Hamilton, A., D.L. Popham, D.J. Carl, X. Lauth, V. Nizet, and A.L. Jones. Penicillin-binding protein 1a promotes resistance of group B Streptococcus to antimicrobial peptides. Infect. Immun. 74:6179-6187. 2006Abstract
  • Priyadarshini, R., D. L. Popham, and K. D. Young. Daughter cell separation by penicillin-binding proteins and peptidoglycan amidases in Escherichia coli. J. Bacteriol. 188:5345-5355. 2006Abstract
  • Gyaneshwar, P., O. Paliy, J. McAuliffe, D.L. Popham, M.I. Jordan, and S. Kustu. Sulfur and nitrogen limitation in Escherichia coli K12 : specific homeostatic responses. J. Bacteriol. 187:1074-1090. 2005.Abstract
  • Silvaggi JM, Popham DL, Driks A, Eichenberger P, Losick R. Unmasking novel sporulation genes in Bacillus subtilis. Journal of Bacteriology. 186(23), 8089-95. 2004.Abstract
  • Wei Y, McPherson DC, Popham DL. A mother cell-specific class B penicillin-binding protein, PBP4b, in Bacillus subtilis. Journal of Bacteriology. 186(1), 258-61. 2004.Abstract
  • Gilmore ME, Bandyopadhyay D, Dean AM, Linnstaedt SD, Popham DL. Production of muramic delta-lactam in Bacillus subtilis spore peptidoglycan. Journal of Bacteriology. 186(1), 80-9. 2004.Abstract
  • Popham DL, Young KD. Role of penicillin-binding proteins in bacterial cell morphogenesis. Current Opinion in Microbiology. 6(6), 594-9. 2003.Abstract
  • Wei Y, Havasy T, McPherson DC, Popham DL. Rod shape determination by the Bacillus subtilis class B penicillin-binding proteins encoded by pbpA and pbpH. Journal of Bacteriology. 185(16), 4717-26. Aug 2003.Abstract
  • McPherson DC, Popham DL. Peptidoglycan synthesis in the absence of class A penicillin-binding proteins in Bacillus subtilis. Journal of Bacteriology. 185(4), 1423-31. Feb 2003.Abstract
  • Popham DL. Specialized peptidoglycan of the bacterial endospore: the inner wall of the lockbox. Cellular and Molecular Life Sciences, 59(3), 426-33. Mar 2002.Abstract
  • Melly E, Genest PC, Gilmore ME, Little S, Popham DL, Driks A, Setlow P. Analysis of the properties of spores of Bacillus subtilis prepared at different temperatures. Journal of Applied Microbiology. 92(6), 1105-15. 2002.Abstract
  • Foster, S. J., and D. L. Popham. Structure and synthesis of cell wall, spore cortex, teichoic acids, S-layers, and capsules. p. 21-41. 2002 In: Bacillus subtilis and Its Close Relatives: From Genes to Cells . A. L. Sonenshein, J. A. Hoch, and R. Losick (ed.), American Society for Microbiology, Washington, D.C.Abstract
  • McPherson DC, Driks A, Popham DL. Two class A high-molecular-weight penicillin-binding proteins of Bacillus subtilis play redundant roles in sporulation. Journal of Bacteriology. 183(20), 6046-53. Oct 2001.Abstract
  • Catalano FA, Meador-Parton J, Popham DL, Driks A. Amino acids in the Bacillus subtilis morphogenetic protein SpoIVA with roles in spore coat and cortex formation. Journal of Bacteriology. 183(5), 1645-54. Mar 2001.Abstract
  • Meador-Parton J, Popham DL. Structural analysis of Bacillus subtilis spore peptidoglycan during sporulation. Journal of Bacteriology. 182(16), 4491-9. Aug 2000.Abstract
  • Popham DL, Meador-Parton J, Costello CE, Setlow P. Spore peptidoglycan structure in a cwlD dacB double mutant of Bacillus subtilis. Journal of Bacteriology. 181(19), 6205-9. Oct 1999.Abstract
  • Popham DL, Gilmore ME, Setlow P. Roles of low-molecular-weight penicillin-binding proteins in Bacillus subtilis spore peptidoglycan synthesis and spore properties. Journal of Bacteriology. 181(1), 126-32. Jan 1999.Abstract
  • Murray T, Popham DL, Pearson CB, Hand AR, Setlow P. Analysis of outgrowth of Bacillus subtilis spores lacking penicillin-binding protein 2a. Journal of Bacteriology. 180(24), 6493-502. Dec 1998.
  • Alban PS, Popham DL, Rippere KE, Krieg NR. Identification of a gene for a rubrerythrin/nigerythrin-like protein in Spirillum volutans by using amino acid sequence data from mass spectrometry and NH2-terminal sequencing. Journal of Applied Microbiology. 85(5), 875-82. Nov 1998.Abstract
  • Murray T, Popham DL, Setlow P. Bacillus subtilis cells lacking penicillin-binding protein 1 require increased levels of divalent cations for growth. Journal of Bacteriology. 180(17), 4555-63. Sep 1998.Abstract
  • Pedersen LB, Murray T, Popham DL, Setlow P. Characterization of dacC, which encodes a new low-molecular-weight penicillin-binding protein in Bacillus subtilis. Journal of Bacteriology. 180(18), 4967-73. Sep 1998.Abstract
  • Murray T, Popham DL, Setlow P. Identification and characterization of pbpA encoding Bacillus subtilis penicillin-binding protein 2A. Journal of Bacteriology. 179(9), 3021-9. May 1997.
  • Popham DL, Helin J, Costello CE, Setlow P. Muramic lactam in peptidoglycan of Bacillus subtilis spores is required for spore outgrowth but not for spore dehydration or heat resistance. Proceedings of the National Academy of Sciences (USA). 93(26), 15405-10. Dec 1996.Abstract
  • Popham DL, Helin J, Costello CE, Setlow P. Analysis of the peptidoglycan structure of Bacillus subtilis endospores. Journal of Bacteriology. 178(22), 6451-8. Nov 1996.Abstract
  • Murray T, Popham DL, Setlow P. Identification and characterization of pbpC, the gene encoding Bacillus subtilis penicillin-binding protein 3. Journal of Bacteriology. 178(20), 6001-5. Oct 1996.Abstract
  • Popham DL, Setlow P. Phenotypes of Bacillus subtilis mutants lacking multiple class A high-molecular-weight penicillin-binding proteins. Journal of Bacteriology. 178(7), 2079-2085. Apr 1996.Abstract
  • Popham DL, Sengupta S, Setlow P. Heat, hydrogen peroxide, and UV resistance of Bacillus subtilis spores with increased core water content and with or without major DNA-binding proteins. Applied and Environmental Microbiology. 61(10), 3633-8. Oct 1995.Abstract
  • Popham DL, Illades-Aguiar B, Setlow P. The Bacillus subtilis dacB gene, encoding penicillin-binding protein 5*, is part of a three-gene operon required for proper spore cortex synthesis and spore core dehydration. Journal of Bacteriology. 177(16), 4721-9. Aug 1995.Abstract
  • Popham DL, Setlow P. Cloning, nucleotide sequence, and mutagenesis of the Bacillus subtilis ponA operon, which codes for penicillin-binding protein (PBP) 1 and a PBP-related factor. Journal of Bacteriology. 177(2), 326-35. Jan 1995.Abstract
  • Popham DL, Setlow P. Cloning, nucleotide sequence, mutagenesis, and mapping of the Bacillus subtilis pbpD gene, which codes for penicillin-binding protein 4. Journal of Bacteriology. 176(23), 7197-205. Dec 1994.Abstract
  • Corfe BM, Moir A, Popham D, Setlow P. Analysis of the expression and regulation of the gerB spore germination operon of Bacillus subtilis 168. Microbiology (Reading, England). 140, (Pt 11) 3079-83. Nov 1994.Abstract
  • Popham DL, Setlow P. Cloning, nucleotide sequence, mutagenesis, and regulation of the Bacillus subtilis pbpF gene, which codes for a putative class A high-molecular-weight penicillin-binding protein. Journal of Bacteriology. 175(15), 4870-4876. Aug 1993.Abstract
  • Popham DL, Setlow P. The cortical peptidoglycan from spores of Bacillus megaterium and Bacillus subtilis is not highly cross-linked. Journal of Bacteriology. 175(9), 2767-9. May 1993.Abstract
  • Popham DL, Setlow P. Cloning, nucleotide sequence, and regulation of the Bacillus subtilis pbpE operon, which codes for penicillin-binding protein 4* and an apparent amino acid racemase. Journal of Bacteriology. 175(10), 2917-25. May 1993.Abstract
  • Popham DL, Stragier P. Binding of the Bacillus subtilis spoIVCA product to the recombination sites of the element interrupting the sigma K-encoding gene. Proceedings of the National Academy of Sciences (USA). 89(13), 5991-5. Jul 1992.Abstract
  • Popham DL, Stragier P. Cloning, characterization, and expression of the spoVB gene of Bacillus subtilis. Journal of Bacteriology. 173(24), 7942-9. Dec 1991.Abstract
  • Popham D, Keener J, Kustu S. Purification of the alternative sigma factor, sigma 54, from Salmonella typhimurium and characterization of sigma 54-holoenzyme. Journal of Biological Chemistry. 266(29), 19510-8. Oct 1991.Abstract
  • Wedel A, Weiss DS, Popham D, Droge P, Kustu S. A bacterial enhancer functions to tether a transcriptional activator near a promoter. Science. 248(4954), 486-90. Apr 1990.Abstract
  • Kustu S, Santero E, Keener J, Popham D, Weiss D. Expression of sigma 54 (ntrA)-dependent genes is probably united by a common mechanism. Microbiological Reviews. 53(3), 367-76. Sep 1989.Abstract
  • Popham DL, Szeto D, Keener J, Kustu S. Function of a bacterial activator protein that binds to transcriptional enhancers. Science. 243(4891), 629-35. Feb 1989.Abstract
  • Wong PK, Popham D, Keener J, Kustu S. In vitro transcription of the nitrogen fixation regulatory operon nifLA of Klebsiella pneumoniae. Journal of Bacteriology. 169(6), 2876-80. Jun 1987.Abstract
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