Grund, M., Kramarska, E., Choi, S. J., McNitt, D. H., Klimko, C. P., Rill, N. O., Dankmeyer, J. L., Shoe, J. L., Hunter, M., Fetterer, D. P., Hedrick, Z. M., Velez, I., Biryukov, S. S., Cote, C. K., Berisio, R., and Lukomski S. (2021) Predictive and experimental immunogenicity of Burkholderia collagen-like protein 8-derived antigens. Vaccines. 9: 1219.
Pilapitiya, D. H., Harris, P. W. R., Hanson-Manful, P., McGregor, R., Kowalczyk, R., Raynes, J. M., Carlton, L. H., Dobson, R. C. J., Baker, M. G., Brimble, M., Lukomski, S., and Moreland, N. (2021) Antibody responses to collagen peptides and streptococcal collagen-like 1 proteins in acute rheumatic fever patients. J. Pathog Dis. 79: ftab033.
Ahmad, R. S., Eubank, T. D., Lukomski, S., and Boone, B. A. (2021) Immune cell modulation of the extracellular matrix contributes to the pathogenesis of pancreatic cancer biomolecules. Biomolecules 11:901.
Grund, M., Choi, S. J., Cote, C. K., Berisio, R., and Lukomski S. (2021) Thinking outside the bug: targeting outer membrane proteins for Burkholderia vaccines. Cells. 10: 495. /review/
Grund, M. E., Choi, S. J., McNitt, D. H., Barbier, M., Hu, G., LaSala, P. R., Cote, C. K., Berisio, R., Lukomski, S. 2020. Burkholderia collagen-like protein 8, Bucl8, is a unique outer membrane component of a putative tetrapartite efflux pump in Burkholderia pseudomallei and Burkholderia mallei. PLoS One. 15: e0242593.
Lukomski, S. and McNitt, D. H. (2020). Expression and Purification of Collagen-like Proteins of Group A Streptococcus. In Group A Streptococcus: methods and protocols (Proft, T. and Loh J. edts). Methods Mol. Biol. 2136:163-179.
McNitt D. H., Choi S. J., Allen, J. L., Hames, R. A., Weed, S. A., Van De Water, L., Berisio R., and Lukomski S. (2019) Adaptation of the group A Streptococcus adhesin Scl1 to bind fibronectin type III repeats within wound-associated extracellular matrix: implications for cancer therapy. Mol. Microbiol. 112: 800-819.
McNitt, D. H., Van De Water, L., Marasco, D., Berisio, R., Lukomski, S. (2018). Streptococcal collagen-like protein 1 binds wound fibronectin: implications in pathogen targeting. Curr Med Chem. 26:1933-1945. /review/
McNitt, D. H., Choi, S. J., Keene, D., Van De Water, L., Squeglia, F., Berisio, R., Lukomski, S. (2018). Surface-exposed loops and an acidic patch in the Scl1 protein of group A Streptococcus enable Scl1 binding to wound-associated fibronectin. J. Biol. Chem. 293: 7796-7810.
Lukomski S., Bachert B. A., Squeglia F., and Berisio R. (2017). Collagen-like proteins of pathogenic streptococci. Mol. Microbiol. 103: 919-930. /review/
Bachert B. A., Choi S. J., LaSala P. R., Harper T. I., McNitt D. H., Boehm D. T., Caswell C. C., Ciborowski P., Keene D. R., Flores A. R., Musser J. M., Squeglia F., Marasco D., Berisio R., and Lukomski S. (2016) Unique footprint in the scl1.3 locus affects adhesion and biofilm formation of the invasive M3-type group A Streptococcus. Front. Cell. Infect. Microbiol. 31: e90.
Bachert, B. A., Choi, S-J., Snyder, A. K., Rio, R. V., Durney, B. C., Holland, L. A., Amemiya, K., Welkos, S. L., Bozue, J. A., Cote, C. K., Berisio, R,. Lukomski, S. (2015) A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection. PLoS One 10:e0137578.
Durney, B., Bachert, B., Sloane, H., Lukomski, S., Landers, J., and Holland, L. (2015) Reversible phospholipid nanogels for accurate DNA fragment size determinations up to 1,500 base pairs and integrated sample stacking. Anal. Chem. Acta 880:136-44.
Flores, A. R., Jewell, B. E., Versalovic, E. M, Olsen, R. J., Bachert, B. A., Lukomski, S., and Musser, J. M. (2015) Natural variant of collagen-like protein A in serotype M3 group A Streptococcus carrier strains enhances colonization and decreases invasive potential. Infect. Immun. 83:1122-9.
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.
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.
The Lukomski Lab at West Virginia University focuses its research on vaccine development against Burkholderia, Streptococcus, and cancer.
Burkholderia vaccine: Burkholderia pseudomallei and Burkholderia mallei are highly infective and intrinsically multidrug resistant bacteria declared by CDC as Category B Bioterrorism Agents. B. pseudomallei causes melioidosis, a disease with a global burden of 89,000 deaths per year, which has primarily been reported in the soil of tropical regions of Southeast Asia and northern Australia. Recent studies indicated melioidosis was markedly underreported in South and Latin America, including Mexico and Caribbean. B. mallei, a causative agent of glanders, is an obligate mammalian pathogen, which typically infects equines and can be transmitted to humans. Infections with both species require extensive antibiotic treatment regiments and have high mortality rates. Currently, there is no vaccine against B. pseudomallei or B. mallei, and no vaccine candidates have been tested in humans. Development of a vaccine able to elicit humoral and cell-mediated immunity is essential for protection of humans in cases of natural infection, as well as in a bioterrorism attack. In addition, multidrug resistant Burkholderia cepacia complex (BCC) species cause pneumonia in patients with underlying diseases, like cystic fibrosis or chronic granulomatous disease.
Our laboratory has identified and modeled the Bucl8 outer-membrane protein. The Bucl8 is a surface-exposed homotrimeric protein, which assembles a periplasmic alpha-helical channel and outer membrane beta barrel with conserved surface-exposed loops and extracellular C-terminal domain. We hypothesize that the Bucl8-derived antigens in combination with an adjuvant will induce a combined humoral and cell-mediated (Th1/Th2) response. The goal of our research is to develop an effective vaccine to fight these deadly infections, helping everyone from cystic fibrosis patients, travelers, deployed military personnel, and rural farmers.
Streptococcal vaccine: Streptococcus pyogenes or group A Streptococcus (GAS), a gram-positive bacterial pathogen, has a significant impact on human morbidity and mortality with over 700 million cases per year globally. The organism is responsible for the superficial infections of the throat and skin, as well as traumatic diseases, such as necrotizing fasciitis and toxic shock syndrome that require extensive tissue debridement and limb amputations. Furthermore, untreated GAS infections may culminate into post-infectious autoimmune sequela, acute rheumatic fever and rheumatic heart disease. Invasive infections and rheumatic heart diseases account for an estimated 517,000 deaths annually worldwide. In the United States, there are more than 10 million cases of supportive throat and skin infections caused by GAS with healthcare costs approaching $500 million.
The immunogenic surface M protein serves as the basis for most GAS vaccine candidates, as it confers M type-specific immunity. The main challenge behind this concept is a high number (>200) of M protein types and differences in M-type distribution across the globe. Our approach employs constructing monomeric IgG scaffolds directed against GAS-surface protein Scl1 to target phylogenetically diverse GAS M types, thus, overcoming difficulties in vaccine development based on M protein.
Cancer Research: Our research aims to develop effective treatment options for cancer patients. To target tumor sites, drugs are conjugated to carriers that recognize the tumor microenvironment, such as overexpressed cell-surface and secreted markers. However, current cancer biomarkers still pose a significant off-target risk due to their expression on healthy cells. Defined isoforms of the extracellular matrix proteins, oncofetal fibronectin, have shown premise as target for the delivery of drugs to tumor microenvironment, and with markedly reduced off-target effects. Recombinant proteins derived from bacterial protein Scl1, studied in our laboratory, bind oncofetal fibronectin. Our research is to design and produce non-toxic nanoparticles, functionalized with rScl1, for targeting tumor microenvironment.
Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy with high mortality. Pancreatic cancer is the third leading cause of cancer death with a 5-year survival rate of only 10% due to a propensity for metastatic spread and resistance to therapy. Despite recent advances, outcomes for patients with PDA remain poor with existing therapies. Dr. William B. Coley, a 19th century sarcoma surgeon, introduced the concept of therapeutic infection of cancers with live group A streptococci or by injecting killed “Coley’s Toxin” as immunotherapy. Recent research has shown that intratumoral injection of GAS to murine subcutaneous pancreatic tumors resulted in regression of the PDA tumor. Suggested mechanisms driving this phenomenon included direct lysis of tumor cells by GAS, upregulation of pro-inflammatory cytokines, and generation lymphocyte mediated immune recognition of the tumor and enhanced infiltration into to the tumor. Therapeutic targeting of GAS-Scl1 complex to the tumor could eliminate off-target effects and unlock potential for combination treatments with immunotherapy or cytotoxic agents directed to the tumor.