Dr. Mahfuzur Sarker, Professor
||216 Dryden Hall
||Ph.D. University of Tokushima, Japan
Research Interests: Bacterial pathogenesis; Molecular pathogenesis of Clostridium perfringens isolates associated with food poisoning and non-food borne gastrointestinal (GI) diseases in humans, and GI diseases in domestic animals; Mechanisms of C. perfringens sporulation, spore germination, and spore resistance.
Courses Taught: MB 440/540 Food Microbiology
My laboratory group investigates the molecular pathogenesis of C. perfringens type A isolates associated with C. perfringens type A food poisoning and non-food-borne gastrointestinal (GI) diseases in humans and GI Diseases in domestic animals. Specifically, we investigate the molecular mechanisms of (1) C. perfringens sporulation (2) spore germination, and (3) spore resistance to various stress factors such as chemicals, heat, and high pressure processing. The gram-positive, spore-forming, anaerobic C. perfringens bacteria is an important cause of both histotoxic and GI diseases in humans and domestic animals. C. perfringens spores are metabolically dormant, are resistant to many environmental insults, and can survive for long periods. Once conditions are favorable, these spores can germinate, outgrow, return to vegetative growth and then release toxins and cause disease. We have shown that C. perfringens spores are resistant to heat, chemicals, UV-radiation and high hydrostatic pressure processing, and the main factors involved in these resistance processes are: (1) the small-acid soluble proteins (SASPs) that saturate the spore’s DNA; (2) a low spore core water content that protects essential enzymes and DNA in the spore core from environmental insults and is controlled in part by SpmA-B and DacB proteins, (3) the spore's large depot of pyridine-2,6-dicarboxylicacid (dipicolinic acid (DPA)) which is pumped into the spore core during sporulation at least in part by the SpoVA proteins.
One approach to develop efficient therapies against C. perfringens diseases is to block or induce spore germination. Blocking spore germination would block the resumption of growing vegetative cells. However, inducing germination would yield spores that have lost their resistance properties to conventional treatments applied in the food industry and in clinical settings, and thus becoming more sensitive to inactivation by milder treatments. Therefore, basic knowledge on the mechanism of spore germination is warranted. In this respect, we identified the nutrient germinants (KCl and a mixture of L-asparagine and KCl) and their cognate receptors (GerKA and/or GerKC) required for C. perfringens spore germination. In a following project, we showed that in C. perfringens: (1) SpoVA proteins are essential for Ca-DPA uptake by the developing spore during C. perfringens sporulation; and (2) SpoVA proteins and Ca-DPA release required for Bacillus subtilis signal transduction, are not required for the transduction of the germination signal from the receptors to the cortex-lytic enzymes (CLEs) during C. perfringens spore germination. Recently, we have also found that SleC is an essential CLE for cortex peptidoglycan (PG) hydrolysis during germination of spores of C. perfringens. The hydrolysis of PG is the culminating event in the germination of bacterial spores, and is essential for resumption of enzymatic activity in the spore core and eventual vegetative growth. As a consequence, cortex hydrolysis is essential for spores of C. perfringens to cause disease. The identification of SleC as the major essential CLE in C. perfringens spores thus makes this enzyme of potential interest for development of inhibitors, since such compounds would block spore germination and thus the ability of spores to cause disease. Cortex hydrolysis also makes the now fully germinated spore much less resistant to common decontamination procedures. Consequently, a drug that could rapidly activate SleC in spores would also be useful, since such a drug would allow decontamination of the now germinated C. perfringens spores under less harsh conditions than needed for destruction of the much more resistant dormant spores.
C. perfringens type A food poisoning currently ranks as the third most commonly reported food-borne disease in the United States. In the U.S. alone C. perfringens type A food poisoning results in annual economic losses of over $120 million dollars. The development of preventive measures against C. perfringens-mediated diseases has been hampered by the lack of understanding of the molecular mechanisms of C. perfringens spore-formation, -germination and -resistance. We anticipate that our research will facilitate the designing and developing of preventive measures against Clostridial diseases.
Deng, K., Talukdar, P.K., Sarker, M.R., Paredes-Sabja, D., Torres, J.A. 2017. Survival of Clostridium difficile spores at low water activity. Food Microbiol. 65:274-278.
Talukdar, P.K., Udompijitkul, P., Hossain, A., and Sarker, M.R. 2016. Inactivation strategies for Clostridium perfringens spores and vegetative cells. Appl. Environ. Microbiol. 83(1). pii:e02731-16. PMID: 27795314.
Mora-Uribe, P., Miranda-Cárdenas, C., Castro-Córdova, P., Gil, F., Calderón, I., Fuentes, J.A., Rodas, P.I., Banawas, S., Sarker, M.R. and Paredes-Sabja, D. 2016. Characterization of the adherence of Clostridium difficile spores: The integrity of the outermost layer affects adherence properties of spores of the epidemic strain R20291 to components of the intestinal mucosa. Front Cell Infect. Microbiol. 6:99.
Banawas, S., Paredes-Sabja, D., Setlow, P., and Sarker, M.R. 2016. Characterization of germinants and their receptors for spores of non-food-borne Clostridium perfringens strain F4969. Microbiol. 162(11):1972-1983.
Li, J., Paredes-Sabja, D., Sarker, M.R. and McClane, B.A. 2016. Clostridium perfringens sporulation and sporulation-associated toxin production. Microbiol. Spectr. 4(3). PMID: 27337447.
Doona, C.J., Feeherry, F.E., Setlow, B., Wang, S., Li, W. Nichols, F.C., Talukdar, P.K., Sarker, M.R., Li, Y.Q., Shen, A., and Setlow, P. 2016. Effects of high-pressure treatment on spores of Clostridium species. Appl. Environ. Microbiol. 82(17):5287-97.
Yasugi, M., Okuzaki, D., Kuwana, R., Takamatsu, H., Fujita, M., Sarker, M.R. and Miyake, M. 2016. Transcriptional profile during deoxycholate-induced sporulation in a Clostridium perfringens isolate causing foodborne illness. Appl. Environ. Microbiol. 82(10):2929-42.
Sarker, M.R., Franks, S., Sumien, N., Thangthaeng, N., Filipetto, F., and Forster, M. 2015. Curcumin mimics the neurocognitive and anti-inflammatory effects of caloric restriction in mouse model of midlife obesity. PLoS One. 10(10):e0140431.
Banawas, S., Korza, G., Paredes-Sabja, D., Li, Y., Hao, B., Setlow, P. and Sarker, M.R. 2015. Location and stoichiometry of the protease CspB and the cortex-lytic enzyme SleC in Clostridium perfringens spores. 2015. Food Microbiol. 50:83-7.
Yasugi, M., Suigahara, Y., Hoshi, H., Kondo, K., Talukdar, P.K., Sarker, M.R., Yamamoto, S., Kamata, Y. and Miyake, M. 2015. In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production. Microb. Pathog. 85:1-10.
Diaz-Gonzalez, F., Milano, M., Olguin-Araneda, V., Pizarro-Cerda, J., Castro-Cordova, P., Tzeng, S.C., Maier, C.S., Sarker, M.R. and Paredes-Sabja, D. 2015. Protein composition of the outermost exosporium-like layer of Clostridium difficile 630 spores. J. Proteomics. 123:1-13.
Alnoman, M., Udfompijitkul, P., Paredes-Sabja, D., and Sarker, M.R. The inhibitory effects of sorbate and benzoate against Clostridium perfringens type A isolates. Food Microbiol. 48:89-98.
Talukdar, P.K., Olguin-Araneda, V., Alnoman, M., Paredes-Sabja, D., and Sarker, M.R. 2014. Updates on the sporulation process in Clostridium species. Res. Microbiol. piiSOp23-2508(14)00250-2.
Aung, K.J., Van Deun, A., Declercq, E., Sarker, M.R., Das, P.K., Hossain, M.A. and Rieder, H.L. 2014. Successful 9-month Bangladesh regimen for multidrug-resistant tuberculosis among over 500 consecutive patients. Int. J. Tuber. Lung Dis. 18(10):1180-7.
Olguin-Araneda, V., Banawas, S., Sarker, M.R. and Paredes-Sabja, D. 2014. Recent advances in germination of Clostridium spores. Res. Microbiol. pii: SO293-2508(14)00119-3.
Sarker, M.R., Islam, K.N., Huri, H.Z., Rahman, M., Imam, H., Hosen, B., Mohammad, N., Sarker, Z.I. 2014. Studies of the impact of occupational exposure of pharmaceutical workers on the development of antimicrobial drug resistance. J. Occup. Hlth. PMID 24953094.
Udompijitkul, P., Alnoman, M., Banawas, S., Paredes-Sabja, D., and Sarker, M.R. 2014. New amino acid germinants for spores of the enterotoxigenic Clostridium perfringens type A isolates. Food Microbiol. 44:24-33.
Akhtar, S., Sarker, M.R., Jabeen, K., Sattar, A., Qamar, A., and Fasih, N. 2014. Antimicrobial resistance in Salmonella enterica serovar typhi and paratyphi in South Asia-current status, issues, and prospects. Crit. Rev. Microbiol. PMID 14645636.
Pizarro-Guajardo, M., Olguín-Araneda, V., Barra-Carrasco, J., Brito-Silva, C.,and Sarker, M.R., 2014. Characterization of the collagen-like exosporium protein, BclA1, of Clostridium difficile spores. Anaerobe 25:18-30.
Li, J., Ma, M., Sarker, M.R., and McClane, B.A. 2013. CodY is a global regulator of virulence-associated properties for Clostridium perfringens type D strain CN3718. MBio. 4(5):e00770-13.
Sarker, M.R., Franks, S., and Caffrey, J. 2013. Direction of post-prandial ghrelin response associated with cortisol respnose, perceived stress and anxiety, and self-reported coping and hunger in obese women. Behav. Brain Res. 257:197-200.
Banawas, S., Paredes-Sabja D., Korza, G., Li, Y., Hao, B., Setlow, P., and Sarker, M.R. 2013. The Clostridium perfringens germinant receptor protein GerKC is located in the spore inner membrane and is crucial for spore germination. J. Bacteriol. 195(22):5084-91.
Barra-Carrasco, J., Olguín-Araneda, V., Plaza-Garrido, A., Miranda-Cárdenas, C., Cofré-Araneda, G., Pizarro-Guajardo, M., Sarker, M.R., and Paredes-Sabja, D. 2013. The Clostridium difficile exosporium cysteine (CdeC)-rich protein is required for exosporium, morphogenesis and coat assembly. J. Bacteriol. 195(17)3863-75.
Sarker, M.R., Akhtar, S., Torres, J.A., and Paredes-Sabja, D. 2013. High hydrostatic pressure-induced inactivation of bacterial spores. Crit. Rev. Microbiol. PMID 23631742.
Ohtani, K., Hirakawa, H., Paredes-Sabja, D., Tashior, K., Kuhara, S., Sarker, M.R. and Shimizu, T. 2013. Unique regulatory mechanism of sporulation and enterotoxin production in Clostridium perfringens. J. Bacteriol. 195(12):2931-6.
Udompijitkul, P., Alnoman, M., and Sarker, M.R. 2013. Inactivation strategy for Clostridium perfringens spores adhered to food contact surfaces. Food Microbiol. 34(2):328-336.
Akhtar, S., Sarker M.R. and Hossain, A. 2012. Microbiological food safety: A dilemma of developing societies. Crit. Rev. Microbiol.
Paredes-Sabja, D., Cofre-Araneda, G., Brito-Silva, C., Pizarro-Guajardo, M., and Sarker, M.R. 2012. Clostridium difficile spore-macrophage interactions: spore survival. PLoS One 7(8):e43635 doi:10.1371 journal pone 0043005.
Sarker, M.R. and Paredes-Sabja, D. 2012. Molecular basis of early stages of Clostridium difficile infection: germination and colonization. Future Microbiol. Aug. 7(8):933-943.
Hernandez-Rocha, C., Barra-Carrasco, J., Pizarro-Guajardo, M., Ibanez, P., Bueno, S.M., Sarker, M.R., Guzman, A.M., Alvarez-Lobos, M., and Paredes-Sabja, D. 2012. Epidemic Clostridium difficile ribotype 027 in Chile. Emerg. Infect. Dis. 18(8):1370-2.
Wang, G., Paredes-Sabja, D., Sarker, M.R., Green, C., Setlow, P., and Li, Y.Q. 2012. Effects of wet heat treatment on the germination of individual spores of Clostridium perfringens. 2012. 3(4):824-36.
Paredes-Sabja, D., and Sarker, M.R. 2012. Adherence of Clostridium difficile spores to Caco-2 cells in culture. J. Med. Microbiol. 6(Pt 9):1208-18.
Mandrell, D., Truong, L., Jephson, C., Sarker, M.R., Moore, A., Lang, C., Simoich, M.T., and Tangua, R.L. 2012. Automated zebrafish chorion removal and single embryo placement: optimizing throughput of zebrafish developmental toxicity screens. J. Lab Autom. 17(1):66-74.
Paredes-Sabja, D. and Sarker, M.R. 2012. Interactions between Clostridium perfringens spores and Raw 264.7 macrophages. Anaerobe 18(1):148-156.
Udompijitkul, P., Paredes-Sabja, D., and Sarker, M.R. 2012. Inhibitory effects of nisin against Clostridium perfringens food poisoning and nonfood-borne isolates. 2012. 77(1):M51-6.
Paredes-Sabja D, and M.R. Sarker. 2011. Host serum factor triggers germination of Clostridium perfringens spores lacking the cortex hydrolysis machinery. J. Med. Microbiol. 2011 Jul 28. [Epub ahead of print]
Yi, X., C. Bond, M.R. Sarker, P. Setlow. 2011. Multivalent metal cations including terbium (Tb3+) can efficiently inhibit the germination of coat-deficient bacterial spores. Appl. Environ. Microbiol. 77(15):5536-5539.
Paredes-Sabja, D. and M.R. Sarker. 2011. Germination response of spores of the pathogenic bacterium Clostridium perfringens and Clostridium difficile to cultured human epithelial cells. Anaerobe.17(2):78-84.
Paredes-Sabja, D., P. Setlow, and M.R. Sarker. 2011. Germination of spores of Bacillales and Clostridiales species: mechanisms and proteins involved. Trends Microbiol. 19:85-94.
Paredes-Sabja, D. and M.R. Sarker. 2010. Effect of the cortex-lytic enzyme SleC from non-food-borne Clostridium perfringens on the germination properties of SleC-lacking spores of a food poisoning isolate. Can. J. Microbiol. 56:952-958.
Akhtar, S., D. Paredes-Sabja, J. A. Torres, and M R. Sarker. 2009. Strategy to inactivate Clostridium perfringens spores in meat products. Food Microbiol. 26:272-277.
Paredes-Sabja, D., P. Setlow, and M.R. Sarker. 2009. SleC is essential for cortex peptidoglycan hydrolysis during germination of spores of the pathogenic bacterium Clostridium perfringens. J. Bacteriol. 191:2711-2720.
Paredes-Sabja, D., P. Setlow, and M.R. Sarker. 2009. Role of GerKB in germination and outgrowth of Clostridium perfringens spores. Appl. Environ. Microbiol. 75:3813-3817.
Paredes-Sabja, D., P. Setlow, and M. R. Sarker. 2009. GerO, a putative Na+/H+-K+ antiporter, is essential for normal germination of spores of the pathogenic bacterium Clostridium perfringens. J. Bacteriol. 191:3822-3831.
Paredes-Sabja, D., and M. R. Sarker. 2009. Clostridium perfringens sporulation and its relevance to pathogenesis. Future Microbiol. 4:519-525.
Li, J., D. Paredes-Sabja, M. R. Sarker, and B. A. McClane. 2009. Further characterization of Clostridium perfringens small acid soluble protein-4 (Ssp4) properties and expression. Plos One. 6(7):e6249.
Paredes-Sabja, D., P. Setlow, and M.R. Sarker. 2009. The protease CspB is essential for initiation of cortex hydrolysis and dipicolinic acid (DPA) release during germination of spores of Clostridium perfringens type A food poisoning isolates. Microbiol. 155:3464-3472.
Paredes-Sabja, D., P. Setlow, and M.R. Sarker. 2009. Inorganic phosphate and sodium ions are cogerminants for spores of Clostridium perfringens type A food poisoning-related isolates. Appl. Environ. Microbiol. 75:6299-6305.
Paredes-Sabja, D., C. Bond, R. J. Carman, P. Setlow, and M.R. Sarker. 2008. Germination of spores of Clostridium difficile strains, including isolates from a hospital outbreak of Clostridium difficile-associated disease (CDAD). Microbiol. 154:2241-2250.
Akhtar, S., D. Paredes-Sabja, and M.R. Sarker. 2008. Inhibitory effects of polyphosphates on Clostridium perfringens growth, sporulation and spore outgrowth. Food Microbiol. 25:802-808.
Paredes-Sabja, D., B. Setlow, P. Setlow, and M.R. Sarker. 2008. Characterization of Clostridium perfringens spores that lack SpoVA proteins and dipicolinic acid. J. Bacteriol. 190:4648-4659.
Paredes-Sabja, D., N. Sarker N, B. Setlow, P. Setlow P, and M.R. Sarker. 2008. Roles of DacB and Spm proteins in Clostridium perfringens spore resistance to moist heat, chemicals, and UV radiation. Appl. Environ. Microbiol. 74:3730-3738.
Paredes-Sabja, D., D. Raju, J. A. Torres, M.R. Sarker. 2008. Role of small, acid-soluble spore proteins in the resistance of Clostridium perfringens spores to chemicals. Int. J. Food Microbiol. 122:333-335.
Paredes-Sabja, D., J. A. Torres, P. Setlow, and M.R. Sarker. 2008. Clostridium perfringens spore germination: characterization of germinants and their receptors. J. Bactriol. 190:1190-1201.
Mendez, M., I. H. Huang, K. Ohtani, R. Grau, T. Shimizu, and M.R. Sarker. 2008. Carbon catabolite repression of type IV pilus-dependent gliding motility in the anaerobic pathogen Clostridium perfringens. J. Bacteriol. 190:48-60.