Most Significant Publications before 2009
Caswell, C.C., Barczyk, M., Keene D.R., Lukomska, E., Gullberg, D.E., and Lukomski, S.(2008) Identification of the first prokaryotic collagen-sequence motif that mediates binding to human collagen receptors, integrins α2β1 and α11β1. J. Biol. Chem. 283: 36168-36175.
Caswell, C. C., Han, R., Hovis, K. M., Lukomska, E., Ciborowski, P., Marconi, R. T., andLukomski, S. (2008) The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement. Mol. Microbiol. 67: 584-596.
Caswell, C. C., Lukomska, E., Seo, N-S., Höök, M., and Lukomski, S. (2007) Scl1-dependent internalization of group A Streptococcus via direct interactions with the α2β1 integrin enhances pathogen survival and reemergence. Mol. Microbiol. 64: 1319-1331.
Han, R., Caswell, C. C., Lukomska, E., Keene, D. R., Pawlowski, M., Bujnicki, J. M., Kim, J. K., and Lukomski, S. (2006) Binding of the low density lipoprotein by streptococcal collagen-like protein Scl1 of Streptococcus pyogenes. Mol. Microbiol. 61: 351-367.
Xu, Y., Keene, D. R., Bujnicki, J. M., Höök, M., and Lukomski, S. (2002) Streptococcal Scl1 and Scl2 proteins form collagen-like triple helices. J. Biol. Chem. 277: 27312-27318.
Hoe, N. P., Nakashima, K., Lukomski, S., Grigsby, D., Liu, M., Kordari, P., Dou, S. J., Pan, X., Vuopio-Varkila, J., Salmelinna, S., McGeer, A., Low, D. E., Schwartz, B., Schuchat, A., Naidich, S., De Lorenzo, D., Fu, Y. X., and Musser, J. M. (1999) Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves. Nature Med. 5: 924-929.
Lukomski, S., Sreevatsan, S., Reichardt, W., Woischnik, M., Podbielski, A., and Musser, J. M. (1997) Inactivation of Streptococcus pyogenes extracellular cysteine protease significantly decreases mouse lethality of serotype M3 and M49 strains. J. Clin. Invest. 99: 2574-2580.
Lukomski, S., and Wells, R. D. (1994) Left-handed Z-DNA and in vivo supercoil density in the E. coli chromosome. Proc. Natl. Acad. Sci. USA 91: 9980-9984.
Recent Significant Publications
Squeglia, F.#, Bachert, B. #, De Simone, A., Lukomski, S., and Berisio, R. (2014) The crystal structure of the streptococcal collagen-like protein 2 globular domain from invasive M3-type Streptococcus pyogenes shows significant similarity to immunomodulatory HIV protein gp41. J. Biol. Chem. 289: 5122-5133.
/#both authors equally contributed to this work/
Tuntevski, K., Durney, B. C., Snyder, A. K., LaSala, P. R., Nayak, A. J., Green, B. J., Beezhold, D. H., Rio, R. V., Holland, L. A., and Lukomski, S. (2013) Aspergillus collagen-like (acl) genes: identification, sequence polymorphism and assessment for PCR-based pathogen detection. App. Environ. Microbiol. 79: 7882-7895.
Squeglia, F., Bachert, B., Romano, M., Lukomski, S., and Berisio, R. (2013) Crystallization and preliminary X-ray crystallographic analysis of the variable domain of Scl2.3, a streptococcal collagen-like protein from invasive M3-type Streptococcus pyogenes. Acta Cryst. F69: 1023-1025.
Oliver-Kozup, H. A., Martin, K. H., Schwegler-Berry, D. E., Green, B. J., Betts, C., Shinde, A. V., Van De Water, L., and Lukomski, S. (2013) The group A streptococcal collagen-like protein 1, Scl1, mediates biofilm formation by targeting the EDA-containing variant of cellular fibronectin expressed in wounded tissue. Mol. Microbiol. 87: 672-689.
Oliver-Kozup, H. A., Elliott, M., Bachert, B. A., Martin, K. H., Reid, S. D., Schwegler-Berry, D. E., Green, B. J., and Lukomski, S. 2011. The streptococcal collagen-like protein-1 (Scl1) is a significant determinant for biofilm formation by group A Streptococcus. BMC Microbiology 11: 262.
Olson, J. C., Cuff, C. F., Lukomski, S., Lukomska, E., Canizales, Y., Wu, B., Crout, R. J, Thomas, J. G., McNeil, D. W., Weyant, R. J, Marazita, M. L., Paster, B. J., and Elliott, T. 2011. Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia. BMC Oral Health 11: 7.
Reuter, M., Caswell, C.C., Lukomski, S., and Zipfel P.F. (2010) Binding of the human complement regulators CFHR1 and factor H by streptococcal-collagen-like protein 1, Scl1, via their conserved C-termini allows control of the complement cascade at multiple levels. J. Biol. Chem. 285: 38473-38485.
Caswell, C. C., Oliver-Kozup, H., Han, R., Lukomska, E., and Lukomski, S. (2010) Scl1, the multifunctional adhesin of group A Streptococcus selectively binds cellular fibronectin and laminin, and mediates pathogen internalization by human cells. FEMS Microbiol. Lett. 303: 61-68.
Leski, T. A., Caswell, C. C., Pawlowski, M., Klinke, D. J., Bujnicki, J. M., Hart, S. J.,and Lukomski, S. (2009). Identification and classification of bcl genes and proteins of Bacillus cereus group organisms and their application in Bacillus anthracis detection and fingerprinting. App. Environ. Microbiol. 75: 7163-7172.
Earlier Significant Publications
Hoe, N. P., Lukomska, E., Musser, J. M., and Lukomski, S. (2007) Characterization of the immune response to collagen-like proteins Scl1 and Scl2 of serotype M1 and M28 group A Streptococcus. FEMS Microbiol. Lett. 277: 142-149.
Mohs, A., Silva, T., Yoshida, T., Lukomski, S., Inouye, M., and Brodsky, B. (2007) Alternative mechanism of stabilization of a bacterial collagen triple-helix in absence of hydroxyproline. J. Biol. Chem. 282: 29757-29765.
Påhlman, L. I., Marx, P. F., Mörgelin, M., Lukomski, S., Meijers, J. C. M., and Herwald, H. (2007) Thrombin Activatable Fibrinolysis Inhibitor binds to Streptococcus pyogenesby interacting with collagen-like proteins A and B. J. Biol. Chem. 282: 24873-24881.
Han, R., Zwiefka, A., Caswell, C. C., Xu, Y., Keene, D. R., Lukomska, E., Zhao, Z., Höök, M., and Lukomski, S. (2006) Assessment of prokaryotic collagen-like sequences derived from streptococcal Scl1 and Scl2 proteins as a source of recombinant GXY polymers. Appl. Microbiol. Biotechnol. 72: 109-115.
Humtsoe, J. O. Kim J. K., Xu, Y., Keene, D. R., Höök, M., Lukomski, S. and Wary, K. K. (2005) A streptococcal collagen-like protein interacts with α2β1 integrin and induces intracellular signaling. J. Biol. Chem. J. Biol. Chem. 280:13848-13857.
Reid, S. D., Montgomery, A. G., Voyich, J. M., DeLeo, F. R., Lei, B., Ireland, R. M., Green, N. M., Liu, M., Lukomski, S., and Musser, J. M. (2003) Characterization of an extracellular virulence factor made by group A Streptococcus with homology to the Listeria monocytogenes internalin family of proteins. Infect. Immun. 71: 7043-7052.
Lukomski, S., Nakashima, K., Abdi, I., Cipriano, V. J., Shelvin, B. J., Graviss, E. A., and Musser, J. M. (2001) Identification and characterization of a second extracellular collagen-like protein made by group A Streptococcus: control of production at the level of translation. Infect. Immun. 69: 1729-1738.
Lukomski, S., Nakashima, K., Abdi, I., Cipriano, V. J., Ireland, R. M., Reid, S. D., Adams, G. G., and Musser, J. M. (2000) Identification and characterization of the scl gene encoding a group A Streptococcus extracellular protein virulence factor with similarity to human collagen. Infect. Immun. 68: 6542-6553.
Lei, B., Mackie, S., Lukomski, S., and Musser, J. M. (2000) Identification and immunogenicity of group A Streptococcus culture supernatant proteins. Infect. Immun. 68: 6807-6818.
Lukomski, S., Hoe, N. P., Abdi, I., Rurangirwa, J., Kordari, P., Liu, M., Shu-Jun, D., Adams, G. G., and Musser, J. M. (2000) Nonpolar inactivation of the hypervariable streptococcal inhibitor of complement gene (sic) in serotype M1 Streptococcuspyogenes significantly decreases mouse mucosal colonization. Infect. Immun. 68: 535-542.
Lukomski, S., Montgomery, C. A., Rurangirwa, J., Geske, R. S., Barrish, J. P., Adams, G. J., and Musser, J. M. (1999) Extracellular cysteine protease produced by Streptococcus pyogenes participates in the pathogenesis of invasive skin infection and dissemination in mice. Infect. Immun. 67: 1779-1788.
Lukomski, S., Burns, E. H., Jr., Wyde, P. R., Rurangirwa, J., Moore-Poveda, D. K., and Musser, J. M. (1998) Genetic inactivation of extracellular cysteine protease, SpeB, of Streptococcus pyogenes decreases resistance to phagocytosis and dissemination to organs. Infect. Immun. 66: 771-776.
Lukomski, S., Hull, R. A., and Hull, S. I. (1996) Identification of the O antigen polymerase (rfc) gene in Escherichia coli O4 by insertional mutagenesis using a nonpolar chloramphenicol resistance cassette. J. Bacteriol. 178: 240-247.
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My research has been aimed at understanding fundamental molecular mechanisms of bacterial pathogenesis, including adhesion and host colonization, immune evasion, and toxicity. Our laboratory studies pathogenicity factors of a Gram-positive bacterium, group A Streptococcus(GAS), including cysteine protease SpeB, complement inhibitor Sic, and structure-function relationship of collagen-like proteins Scl1 and Scl2. Additional projects are conducted in association with WVNano Initiative and include pathogen detection based on sequence polymorphisms in collagen-like genes.
The Scl1 protein selectively binds to human extracellular matrix (ECM) component, cellular fibronectin (cFn) and laminin. GAS wild-type strains form rich biofilm on cFn-coated surface, whereas biofilms formed by scl1 mutants are significantly decreased. Human cells deposit a cFn-rich natural ECM with distinct supramolecular structure, and GAS cells preferentially recognize and attach to this structure. Altogether, (i) Scl1 surface protein is an essential determinant of GAS biofilm and (ii) Scl1-cFn interaction provides an adherence mechanism for biofilm stability facilitating host colonization.
Affinity chromatography and mass spectrometry analyses identified that some Scl1 variants bind factor H (CFH) and factor H-related protein 1 (CFHR-1), while other variants bind the low density lipoprotein (LDL). CFH binding affects complement activation at the level of C3 convertase, while CFHR-1 binding affects complement activation at the C5 level and has not been previously described for GAS. We hypothesize that simultaneous Scl1-mediated binding of CFH and CFHR-1 to GAS surface may provide novel binary mechanism of immune evasion.
Scl1 binding to LDL occurs via the apolipoprotein B100 component. The wild type strain, but not the isogenic Scl1-deficient mutant, adsorbed LDL on the GAS cell surface. This project is aimed at investigating the role of blood LDL as a component of innate immune system during group A Streptococcus infection.
Pathogen detection based on sequence polymorphisms in collagen-like genes
We evaluated sequence polymorphisms of the Bacillus collagen-like genes, bcl A-E, as a basis forB. anthracis detection and fingerprinting. Sequence polymorphisms were identified within bclBalleles that allowed for the specific detection of B. anthracis strains by PCR using both purified DNA and spores as templates. In addition, multiplex PCR of bclA-E genes generate markedly different fingerprints for B. anthracis strains.
Aspergillus collagen-like gene, designated aclF1, was identified in A. fumigatus genome. PCR amplification of the 5’ and 3’ regions of aclF1 gene yielded predicted amplicons in all A. fumigatus samples tested, but not in the control samples. This pilot study identifies aclF1 gene as a candidate biomarker for species-specific detection of A. fumigatus infections in humans.