Natalia Korotkova | Molecular & Cellular Biochemistry

Natalia Korotkova

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nkorotkova@uky.edu

859-323-5493

BBSRB B279

Position(s):

Research Faculty

Affiliation(s):

Microbiology, Immunology & Molecular Genetics

Research Description:

The major focus of my research program is to understand the organization and functioning of cell wall envelope in streptococci and other medically important Gram-positive pathogens with the purpose of development of highly targeted therapeutics to control infections caused by these bacteria.

The plasma membrane of Gram-positive bacteria is surrounded by thick cell wall that consists of a complex network of peptidoglycan with covalently attached polysaccharides. While peptidoglycan is very well studied, the structures and biosynthesis of the polysaccharides remain largely unexplored in many Gram-positive bacteria. These polysaccharides play critical functions in cell division, antibiotic resistance, metal ion homeostasis, and protection of bacteria from host defense peptides and antimicrobial enzymes. These structures and their biosynthetic pathways are attractive targets for therapeutic intervention, such as antibiotic development and vaccine design.

We work with important human pathogens: Streptococcus pyogenes, Streptococcus mutans, Streptococcus agalactiae, Streptococcus pneumoniae and Enterococcus faecalis.

Selected Publications:

Edgar RJ, van Hensbergen VP, Ruda A, Turner AG, Deng P, Le Breton Y, El-Sayed NM, Belew AT, McIver KS, McEwan AG, Morris AJ, Lambeau G, Walker MJ, Rush JS, Korotkov KV, Widmalm G, van Sorge NM, Korotkova N. Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides. (2019) Nature Chemical Biology 15(5): 463-471. PMID: 30936502

Rush JS, Edgar RJ, Deng P, Chen J, Zhu H, van Sorge NM, Morris AJ, Korotkov KV, Korotkova N. The molecular mechanism of N-acetylglucosamine side-chain attachment to the Lancefield group A carbohydrate in Streptococcus pyogenes. (2017) Journal of Biological Chemistry 292(47): 19441-19457. PMID: 29021255

Edgar RJ, Chen J, Kant S, Rechkina E, Rush JS, Forsberg LS, Jaehrig B, Azadi P, Tchesnokova V, Sokurenko EV, Zhu H, Korotkov KV, Pancholi V, Korotkova N. SpyB, a small heme-binding protein, affects the composition of the cell wall in Streptococcus pyogenes. (2016) Frontiers in Cellular and Infection Microbiology 6: 126. PMID: 27790410

Falaleeva M, Zurek OW, Watkins RL, Reed RW, Ali H, Sumby P, Voyich JM, Korotkova N. Transcription of the Streptococcus pyogenes hyaluronic acid capsule biosynthesis operon is regulated by previously unknown upstream elements. (2014) Infection and Immunity 82(12): 5293-307. PMID: 25287924

Complete list of publications: PubMed

PubMed Publications:

Williamson, ZA ; Chaton, CT ; Ciocca, WA ; Korotkova, N.; Korotkov, KV "PE5-PPE4-EspG3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems." The Journal of biological chemistry 295, 36 (2020): 12706-12715. [PubMed Link] | [ Full text ]
Boyd, JD ; Korotkova, N.; Grady, ME "Adhesion of biofilms on titanium measured by laser-induced spallation." Experimental mechanics 59, 9 (2019): 1275-1284. [PubMed Link] |
Edgar, RJ ; van Hensbergen, VP ; Ruda, A ; Turner, AG ; Deng, P.; Le Breton, Y ; El-Sayed, NM ; Belew, AT ; McIver, KS ; McEwan, AG ; Morris, AJ ; Lambeau, G.; Walker, MJ ; Rush, JS ; Korotkov, KV ; Widmalm, G ; Sorge, NM ; Korotkova, N. "Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides." Nature chemical biology 15, 5 (2019): 463-471. [PubMed Link] | [ Full text ]
Rush, JS ; Edgar, RJ ; Deng, P.; Chen, J.; Zhu, H.; Sorge, NM ; Morris, AJ ; Korotkov, KV ; Korotkova, N. "The molecular mechanism of N-acetylglucosamine side-chain attachment to the Lancefield group A carbohydrate in Streptococcus pyogenes." The Journal of biological chemistry 292, 47 (2017): 19441-19457. [PubMed Link] | [ Full text ]
Edgar, RJ ; Chen, J.; Kant, S.; Rechkina, E.; Rush, JS ; Forsberg, LS ; Jaehrig, B.; Azadi, P.; Tchesnokova, V.; Sokurenko, EV ; Zhu, H.; Korotkov, KV ; Pancholi, V.; Korotkova, N. "SpyB, a Small Heme-Binding Protein, Affects the Composition of the Cell Wall in Streptococcus pyogenes." Frontiers in cellular and infection microbiology 6, (2016): 126. [PubMed Link] |
Korotkova, N.; Piton, J.; Wagner, JM ; Boy-Röttger, S.; Japaridze, A.; Evans, TJ ; Cole, ST ; Pojer, F.; Korotkov, KV "Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis." Journal of structural biology 191, 2 (2015): 236-44. [PubMed Link] | [ Full text ]
Shen, M.; Falaleeva, M.; Korotkova, N.; Stamm, S. "Direct cloning of double-stranded RNAs." Methods in molecular biology (Clifton, N.J.) 1296, (2015): 53-64. [PubMed Link] | [ Full text ]
Korotkova, N.; Freire, D.; Phan, TH ; Ummels, R.; Creekmore, CC ; Evans, TJ ; Wilmanns, M.; Bitter, W.; Parret, AH ; Houben, EN ; Korotkov, KV "Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer." Molecular microbiology 94, 2 (2014): 367-82. [PubMed Link] | [ Full text ]
Falaleeva, M.; Zurek, OW ; Watkins, RL ; Reed, RW ; Ali, H.; Sumby, P.; Voyich, JM ; Korotkova, N. "Transcription of the Streptococcus pyogenes hyaluronic acid capsule biosynthesis operon is regulated by previously unknown upstream elements." Infection and immunity 82, 12 (2014): 5293-307. [PubMed Link] | [ Full text ]
Korotkova, N.; Hoff, JS ; Becker, DM ; Quinn, JK ; Icenogle, LM ; Moseley, SL "SpyA is a membrane-bound ADP-ribosyltransferase of Streptococcus pyogenes which modifies a streptococcal peptide, SpyB." Molecular microbiology 83, 5 (2012): 936-52. [PubMed Link] | [ Full text ]
Le Moal, Liévin- ; Beau, I.; Rougeaux, C ; Kansau, I ; Fabrega, S ; Brice, C ; Korotkova, N.; Moseley, SL ; Servin, AL "Apical expression of human full-length hCEACAM1-4L protein renders the Madin Darby Canine Kidney cells responsive to lipopolysaccharide leading to TLR4-dependent Erk1/2 and p38 MAPK signalling." Cellular microbiology 13, 5 (2011): 764-85. [PubMed Link] | [ Full text ]
Korotkova, N.; Yarova-Yarovaya, Y.; Tchesnokova, V.; Yazvenko, N.; Carl, MA ; Stapleton, AE ; Moseley, SL "Escherichia coli DraE adhesin-associated bacterial internalization by epithelial cells is promoted independently by decay-accelerating factor and carcinoembryonic antigen-related cell adhesion molecule binding and does not require the DraD invasin." Infection and immunity 76, 9 (2008): 3869-80. [PubMed Link] | [ Full text ]
Korotkova, N.; Yang, Y.; Le Trong, I.; Cota, E.; Demeler, B.; Marchant, J.; Thomas, WE ; Stenkamp, RE ; Moseley, SL ; Matthews, S. "Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation." Molecular microbiology 67, 2 (2008): 420-34. [PubMed Link] | [ Full text ]
Korotkova, N.; Chattopadhyay, S.; Tabata, TA ; Beskhlebnaya, V.; Vigdorovich, V.; Kaiser, BK ; Strong, RK ; Dykhuizen, DE ; Sokurenko, EV ; Moseley, SL "Selection for functional diversity drives accumulation of point mutations in Dr adhesins of Escherichia coli." Molecular microbiology 64, 1 (2007): 180-94. [PubMed Link] | [ Full text ]
Korotkova, N.; Cota, E.; Lebedin, Y.; Monpouet, S.; Guignot, J.; Servin, AL ; Matthews, S.; Moseley, SL "A subfamily of Dr adhesins of Escherichia coli bind independently to decay-accelerating factor and the N-domain of carcinoembryonic antigen." The Journal of biological chemistry 281, 39 (2006): 29120-30. [PubMed Link] | [ Full text ]
Korotkova, N.; Le Trong, I.; Samudrala, R.; Korotkov, K.; Van Loy, CP ; Bui, AL ; Moseley, SL ; Stenkamp, RE "Crystal structure and mutational analysis of the DaaE adhesin of Escherichia coli." The Journal of biological chemistry 281, 31 (2006): 22367-77. [PubMed Link] | [ Full text ]
Kalyuzhnaya, MG ; Korotkova, N.; Crowther, G.; Marx, CJ ; Lidstrom, ME ; Chistoserdova, L. "Analysis of gene islands involved in methanopterin-linked C1 transfer reactions reveals new functions and provides evolutionary insights." Journal of bacteriology 187, 13 (2005): 4607-14. [PubMed Link] | [ Full text ]
Korotkova, N.; Lidstrom, ME ; Chistoserdova, L. "Identification of genes involved in the glyoxylate regeneration cycle in Methylobacterium extorquens AM1, including two new genes, meaC and meaD." Journal of bacteriology 187, 4 (2005): 1523-6. [PubMed Link] | [ Full text ]
Korotkova, N.; Lidstrom, ME "MeaB is a component of the methylmalonyl-CoA mutase complex required for protection of the enzyme from inactivation." The Journal of biological chemistry 279, 14 (2004): 13652-8. [PubMed Link] | [ Full text ]
Van Dien, SJ ; Okubo, Y.; Hough, MT ; Korotkova, N.; Taitano, T.; Lidstrom, ME "Reconstruction of C(3) and C(4) metabolism in Methylobacterium extorquens AM1 using transposon mutagenesis." Microbiology (Reading, England) 149, Pt 3 (2003): 601-609. [PubMed Link] | [ Full text ]
Korotkova, N.; Chistoserdova, L.; Lidstrom, ME "Poly-beta-hydroxybutyrate biosynthesis in the facultative methylotroph methylobacterium extorquens AM1: identification and mutation of gap11, gap20, and phaR." Journal of bacteriology 184, 22 (2002): 6174-81. [PubMed Link] | [ Full text ]
Korotkova, N.; Chistoserdova, L.; Kuksa, V.; Lidstrom, ME "Glyoxylate regeneration pathway in the methylotroph Methylobacterium extorquens AM1." Journal of bacteriology 184, 6 (2002): 1750-8. [PubMed Link] | [ Full text ]
Korotkova, N.; Lidstrom, ME "Connection between poly-beta-hydroxybutyrate biosynthesis and growth on C(1) and C(2) compounds in the methylotroph Methylobacterium extorquens AM1." Journal of bacteriology 183, 3 (2001): 1038-46. [PubMed Link] | [ Full text ]