Mark McClain
Last active: 4/26/2016


We are interested in bacterial pathogenesis, with an emphasis in bacterial protein toxins. These proteins play critical roles in infectious diseases, often in the earliest stages of interaction between pathogenic bacteria and the host organism. Current studies focus on toxins produced by the human pathogens Helicobacter pylori and Clostridium perfringens. Through studying such toxins, we expect to better understand the molecular events that contribute to disease and to develop therapeutic inhibitors that will be used to treat disease. One focus of our studies is the Clostridium perfringens epsilon toxin. C. perfringens is a gram positive, anaerobic bacterium that causes a wide variety of illnesses, ranging from diarrhea to lethal toxemias, in humans and other animals. The epsilon toxin is an extremely potent pore-forming toxin responsible for an often fatal enterotoxemia in animals (particularly livestock, but also possibly in humans). Using a high-throughput screen and molecular biological, biochemical, and cell biological techniques, we seek to develop safe and effective inhibitors of the toxin. As we continue to develop inhibitors of the toxin, we hope to understand what makes the epsilon toxin so very potent. A second focus of our studies is the gram negative bacterium Helicobacter pylori, an organism associated with peptic ulcers and gastric cancer in humans. Two proteins secreted by H. pylori are VacA and CagA. VacA is a secreted pore-forming toxin with a variety of effects on epithelial cells. CagA is a protein that is translocated directly from the bacterial cytoplasm into the cytoplasm of host epithelial cells through a specialized secretion apparatus. Using molecular biological, biochemical, and cell biological techniques, our current studies focus on structure-function relationships of the VacA toxin, the type IV secretion apparatus required for CagA secretion, and efforts to identify proteins other than CagA that are translocated by the H. pylori CagA secretion apparatus. As a result of these studies, we hope to better understand the contribution of H. pylori to peptic ulcers and gastric cancer.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin. Rumah KR, Ma Y, Linden JR, Oo ML, Anrather J, Schaeren-Wiemers N, Alonso MA, Fischetti VA, McClain MS, Vartanian T (2015) PLoS Pathog 11(5): e1004896
    › Primary publication · 25993478 (PubMed) · PMC4439126 (PubMed Central)
  2. Role of connexin 43 in Helicobacter pylori VacA-induced cell death. Radin JN, González-Rivera C, Frick-Cheng AE, Sheng J, Gaddy JA, Rubin DH, Algood HM, McClain MS, Cover TL (2014) Infect Immun 82(1): 423-32
    › Primary publication · 24191302 (PubMed) · PMC3911829 (PubMed Central)
  3. Control of gene expression in Helicobacter pylori using the Tet repressor. McClain MS, Duncan SS, Gaddy JA, Cover TL (2013) J Microbiol Methods 95(3): 336-41
    › Primary publication · 24113399 (PubMed) · PMC3856897 (PubMed Central)
  4. Genome Sequences of Three hpAfrica2 Strains of Helicobacter pylori. Duncan SS, Bertoli MT, Kersulyte D, Valk PL, Tamma S, Segal I, McClain MS, Cover TL, Berg DE (2013) Genome Announc 1(5)
    › Primary publication · 24072860 (PubMed) · PMC3784780 (PubMed Central)
  5. Comparative genomic analysis of East Asian and non-Asian Helicobacter pylori strains identifies rapidly evolving genes. Duncan SS, Valk PL, McClain MS, Shaffer CL, Metcalf JA, Bordenstein SR, Cover TL (2013) PLoS One 8(1): e55120
    › Primary publication · 23383074 (PubMed) · PMC3561388 (PubMed Central)
  6. Oligomerization of Clostridium perfringens epsilon toxin is dependent upon caveolins 1 and 2. Fennessey CM, Sheng J, Rubin DH, McClain MS (2012) PLoS One 7(10): e46866
    › Primary publication · 23056496 (PubMed) · PMC3462777 (PubMed Central)
  7. Identification of amino acids important for binding of Clostridium perfringens epsilon toxin to host cells and to HAVCR1. Ivie SE, McClain MS (2012) Biochemistry 51(38): 7588-95
    › Primary publication · 22938730 (PubMed) · PMC3534817 (PubMed Central)
  8. Coenzyme depletion by members of the aerolysin family of pore-forming toxins leads to diminished ATP levels and cell death. Fennessey CM, Ivie SE, McClain MS (2012) Mol Biosyst 8(8): 2097-105
    › Primary publication · 22688384 (PubMed) · PMC3759351 (PubMed Central)
  9. The intermediate region of Helicobacter pylori VacA is a determinant of toxin potency in a Jurkat T cell assay. González-Rivera C, Algood HM, Radin JN, McClain MS, Cover TL (2012) Infect Immun 80(8): 2578-88
    › Primary publication · 22585965 (PubMed) · PMC3434591 (PubMed Central)
  10. Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface. Shaffer CL, Gaddy JA, Loh JT, Johnson EM, Hill S, Hennig EE, McClain MS, McDonald WH, Cover TL (2011) PLoS Pathog 7(9): e1002237
    › Primary publication · 21909278 (PubMed) · PMC3164655 (PubMed Central)
  11. Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity. Loh JT, Shaffer CL, Piazuelo MB, Bravo LE, McClain MS, Correa P, Cover TL (2011) Cancer Epidemiol Biomarkers Prev 20(10): 2237-49
    › Primary publication · 21859954 (PubMed) · PMC3189306 (PubMed Central)
  12. Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Radin JN, González-Rivera C, Ivie SE, McClain MS, Cover TL (2011) Infect Immun 79(7): 2535-43
    › Primary publication · 21482684 (PubMed) · PMC3191986 (PubMed Central)
  13. Gene-trap mutagenesis identifies mammalian genes contributing to intoxication by Clostridium perfringens ε-toxin. Ivie SE, Fennessey CM, Sheng J, Rubin DH, McClain MS (2011) PLoS One 6(3): e17787
    › Primary publication · 21412435 (PubMed) · PMC3055893 (PubMed Central)
  14. Identification of Small Molecule Inhibitors of Clostridium perfringens ε-Toxin Cytotoxicity Using a Cell-Based High-Throughput Screen. Lewis M, Weaver CD, McClain MS (2010) Toxins (Basel) 2(7): 1825-1847
    › Primary publication · 20721308 (PubMed) · PMC2922765 (PubMed Central)
  15. Reconstitution of Helicobacter pylori VacA toxin from purified components. González-Rivera C, Gangwer KA, McClain MS, Eli IM, Chambers MG, Ohi MD, Lacy DB, Cover TL (2010) Biochemistry 49(27): 5743-52
    › Primary publication · 20527875 (PubMed) · PMC2910095 (PubMed Central)
  16. Analysis of a beta-helical region in the p55 domain of Helicobacter pylori vacuolating toxin. Ivie SE, McClain MS, Algood HM, Lacy DB, Cover TL (2010) BMC Microbiol : 60
    › Primary publication · 20178613 (PubMed) · PMC2836311 (PubMed Central)
  17. Dominant-negative inhibitors of the Clostridium perfringens epsilon-toxin. Pelish TM, McClain MS (2009) J Biol Chem 284(43): 29446-53
    › Primary publication · 19720828 (PubMed) · PMC2785577 (PubMed Central)
  18. Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer. McClain MS, Shaffer CL, Israel DA, Peek RM, Cover TL (2009) BMC Genomics : 3
    › Primary publication · 19123947 (PubMed) · PMC2627912 (PubMed Central)
  19. Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells. Loh JT, Torres VJ, Algood HM, McClain MS, Cover TL (2008) FEMS Microbiol Lett 289(1): 53-8
    › Primary publication · 19065710 (PubMed) · PMC2651568 (PubMed Central)
  20. Helicobacter pylori VacA subdomain required for intracellular toxin activity and assembly of functional oligomeric complexes. Ivie SE, McClain MS, Torres VJ, Algood HM, Lacy DB, Yang R, Blanke SR, Cover TL (2008) Infect Immun 76(7): 2843-51
    › Primary publication · 18443094 (PubMed) · PMC2446698 (PubMed Central)
  21. Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Gangwer KA, Mushrush DJ, Stauff DL, Spiller B, McClain MS, Cover TL, Lacy DB (2007) Proc Natl Acad Sci U S A 104(41): 16293-8
    › Primary publication · 17911250 (PubMed) · PMC2042200 (PubMed Central)
  22. Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin. McClain MS, Cover TL (2007) Infect Immun 75(4): 1785-93
    › Primary publication · 17261609 (PubMed) · PMC1865726 (PubMed Central)
  23. Random mutagenesis of Helicobacter pylori vacA to identify amino acids essential for vacuolating cytotoxic activity. McClain MS, Czajkowsky DM, Torres VJ, Szabo G, Shao Z, Cover TL (2006) Infect Immun 74(11): 6188-95
    › Primary publication · 16954403 (PubMed) · PMC1695532 (PubMed Central)
  24. Protein-protein interactions among Helicobacter pylori cag proteins. Busler VJ, Torres VJ, McClain MS, Tirado O, Friedman DB, Cover TL (2006) J Bacteriol 188(13): 4787-800
    › Primary publication · 16788188 (PubMed) · PMC1482994 (PubMed Central)
  25. Mapping of a domain required for protein-protein interactions and inhibitory activity of a Helicobacter pylori dominant-negative VacA mutant protein. Torres VJ, McClain MS, Cover TL (2006) Infect Immun 74(4): 2093-101
    › Primary publication · 16552038 (PubMed) · PMC1418911 (PubMed Central)
  26. Functional properties of the p33 and p55 domains of the Helicobacter pylori vacuolating cytotoxin. Torres VJ, Ivie SE, McClain MS, Cover TL (2005) J Biol Chem 280(22): 21107-14
    › Primary publication · 15817461 (PubMed)
  27. Interactions between p-33 and p-55 domains of the Helicobacter pylori vacuolating cytotoxin (VacA). Torres VJ, McClain MS, Cover TL (2004) J Biol Chem 279(3): 2324-31
    › Primary publication · 14593124 (PubMed)
  28. Expression of Helicobacter pylori vacuolating toxin in Escherichia coli. McClain MS, Cover TL (2003) Infect Immun 71(4): 2266-71
    › Primary publication · 12654854 (PubMed) · PMC152094 (PubMed Central)
  29. Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin. McClain MS, Iwamoto H, Cao P, Vinion-Dubiel AD, Li Y, Szabo G, Shao Z, Cover TL (2003) J Biol Chem 278(14): 12101-8
    › Primary publication · 12562777 (PubMed)
  30. Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts. Schraw W, Li Y, McClain MS, van der Goot FG, Cover TL (2002) J Biol Chem 277(37): 34642-50
    › Primary publication · 12121984 (PubMed)
  31. A 12-amino-acid segment, present in type s2 but not type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation. McClain MS, Cao P, Iwamoto H, Vinion-Dubiel AD, Szabo G, Shao Z, Cover TL (2001) J Bacteriol 183(22): 6499-508
    › Primary publication · 11673417 (PubMed) · PMC95478 (PubMed Central)
  32. Antigenic diversity among Helicobacter pylori vacuolating toxins. Vinion-Dubiel AD, McClain MS, Cao P, Mernaugh RL, Cover TL (2001) Infect Immun 69(7): 4329-36
    › Primary publication · 11401970 (PubMed) · PMC98503 (PubMed Central)
  33. Amino-terminal hydrophobic region of Helicobacter pylori vacuolating cytotoxin (VacA) mediates transmembrane protein dimerization. McClain MS, Cao P, Cover TL (2001) Infect Immun 69(2): 1181-4
    › Primary publication · 11160018 (PubMed) · PMC98002 (PubMed Central)
  34. Acid activation of Helicobacter pylori vacuolating cytotoxin (VacA) results in toxin internalization by eukaryotic cells. McClain MS, Schraw W, Ricci V, Boquet P, Cover TL (2000) Mol Microbiol 37(2): 433-42
    › Primary publication · 10931337 (PubMed)
  35. A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. Vinion-Dubiel AD, McClain MS, Czajkowsky DM, Iwamoto H, Ye D, Cao P, Schraw W, Szabo G, Blanke SR, Shao Z, Cover TL (1999) J Biol Chem 274(53): 37736-42
    › Primary publication · 10608833 (PubMed)
  36. Kinetics and mechanisms of extracellular protein release by Helicobacter pylori. Schraw W, McClain MS, Cover TL (1999) Infect Immun 67(10): 5247-52
    › Primary publication · 10496902 (PubMed) · PMC96877 (PubMed Central)
  37. Extracellular release of antigenic proteins by Helicobacter pylori. Cao P, McClain MS, Forsyth MH, Cover TL (1998) Infect Immun 66(6): 2984-6
    › Primary publication · 9596777 (PubMed) · PMC108299 (PubMed Central)
  38. The role of Legionella pneumophila-infected Hartmannella vermiformis as an infectious particle in a murine model of Legionnaire's disease. Brieland JK, Fantone JC, Remick DG, LeGendre M, McClain M, Engleberg NC (1997) Infect Immun 65(12): 5330-3
    › Primary publication · 9393834 (PubMed) · PMC175767 (PubMed Central)
  39. Intrapulmonary Hartmannella vermiformis: a potential niche for Legionella pneumophila replication in a murine model of legionellosis. Brieland J, McClain M, LeGendre M, Engleberg C (1997) Infect Immun 65(11): 4892-6
    › Primary publication · 9353084 (PubMed) · PMC175705 (PubMed Central)
  40. Humoral immunity and regulation of intrapulmonary growth of Legionella pneumophila in the immunocompetent host. Brieland JK, Heath LA, Huffnagle GB, Remick DG, McClain MS, Hurley MC, Kunkel RK, Fantone JC, Engleberg C (1996) J Immunol 157(11): 5002-8
    › Primary publication · 8943407 (PubMed)
  41. Coinoculation with Hartmannella vermiformis enhances replicative Legionella pneumophila lung infection in a murine model of Legionnaires' disease. Brieland J, McClain M, Heath L, Chrisp C, Huffnagle G, LeGendre M, Hurley M, Fantone J, Engleberg C (1996) Infect Immun 64(7): 2449-56
    › Primary publication · 8698466 (PubMed) · PMC174097 (PubMed Central)
  42. Construction of an alkaline phosphatase fusion-generating transposon, mTn10phoA. McClain MS, Engleberg NC (1996) Gene 170(1): 147-8
    › Primary publication · 8621078 (PubMed)
  43. The Legionella pneumophila hel locus encodes intracellularly induced homologs of heavy-metal ion transporters of Alcaligenes spp. McClain MS, Hurley MC, Brieland JK, Engleberg NC (1996) Infect Immun 64(5): 1532-40
    › Primary publication · 8613357 (PubMed) · PMC173958 (PubMed Central)
  44. Inversion-independent phase variation of type 1 fimbriae in Escherichia coli. McClain MS, Blomfield IC, Eberhardt KJ, Eisenstein BI (1993) J Bacteriol 175(14): 4335-44
    › Primary publication · 8101185 (PubMed) · PMC204873 (PubMed Central)
  45. Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12. Blomfield IC, Calie PJ, Eberhardt KJ, McClain MS, Eisenstein BI (1993) J Bacteriol 175(1): 27-36
    › Primary publication · 8093239 (PubMed) · PMC196094 (PubMed Central)
  46. Shuttle mutagenesis of Legionella pneumophila: identification of a gene associated with host cell cytopathicity. Arroyo J, Hurley MC, Wolf M, McClain MS, Eisenstein BI, Engleberg NC (1994) Infect Immun 62(9): 4075-80
    › Primary publication · 8063428 (PubMed) · PMC303072 (PubMed Central)
  47. Type 1 fimbriae mutants of Escherichia coli K12: characterization of recognized afimbriate strains and construction of new fim deletion mutants. Blomfield IC, McClain MS, Eisenstein BI (1991) Mol Microbiol 5(6): 1439-45
    › Primary publication · 1686292 (PubMed)
  48. Roles of fimB and fimE in site-specific DNA inversion associated with phase variation of type 1 fimbriae in Escherichia coli. McClain MS, Blomfield IC, Eisenstein BI (1991) J Bacteriol 173(17): 5308-14
    › Primary publication · 1679430 (PubMed) · PMC208240 (PubMed Central)
  49. Type 1 fimbriation and fimE mutants of Escherichia coli K-12. Blomfield IC, McClain MS, Princ JA, Calie PJ, Eisenstein BI (1991) J Bacteriol 173(17): 5298-307
    › Primary publication · 1679429 (PubMed) · PMC208239 (PubMed Central)