Research:
Dr. Carleen Collins received her Ph.D. in microbiology from UCLA and did her postdoctoral work at Stanford Medical School.
The research focus of my laboratory is to understand the molecular mechanisms of bacterial virulence, with a specific emphasis on the activities and structures of bacterial exotoxins. Over the years we have examined the exotoxins of the Gram-positive pathogens Staphylococcus aureus, a ubiquitous bacterium that causes a wide spectrum of disease including infections of the skin, food poisoning and toxic shock syndrome and Streptococcus pyogenes the culprit of a wide range of pathologies from relatively mild “strep throat” to severe life threatening necrotizing fasciitis and streptococcal toxic shock syndrome. Currently the laboratory is focusing on a novel streptococcal toxin termed SpyA. SpyA is an ADP-ribosyltransferase that modifies host cell cytoskeletal proteins such as vimentin, actin and tropomyosin. Modification of these cytoskeletal proteins suggests that the toxin inhibits internalization or clearance of this bacterium by the host cells. This toxin has a unique entry mechanism, in that it does not contain a classical B or receptor-binding domain, but rather gets into the cell using a cytolysin-produced pore. We are examining the role of this toxin in streptococcal disease, the biochemical and structural properties of SpyA, and the mechanism of toxin entry.
The laboratory has a distinct second line of research, focusing on a family of insecticidal toxins synthesized by various members of the Enterobacteriaceae. The insect pathogen Photorhabdus luminescens as well as members of the pathogenic Yersiniae, including Yersinia pestis, the causative agent of bubonic plague, produce this complex. Similar to our studies with SpyA, we are interested in the specific interactions of these toxins with host cells. Experiments to determine the biochemical activities and structures of these complexes are being performed.
Selected Publications:
Gendlina, I., Held, K.G., Bartra, S.S., Gallis, B.M, Doneanu, C.E., Goodlett, D.R., Gregory V. Plano, G.V., and Collins, C.M. (2007) Identification and Type III dependent secretion of the Yersinia pestis insecticidal-like proteins. Mol Microbiol, 64:1214-1227.
Held, K.G., LaRock, C.N., D’Argenio, D. A., Berg, C. A. and Collins, C.M. A metalloprotease secreted by the insect pathogen Photorhabdus luminescens induces melanization. Submitted.
Coye, L.H. and Collins, C.M. (2004) Identification of SpyA, a novel ADP-ribosyltransferase of Streptococcus pyogenes. Mol Microbiol. 54:89-98.
Baker, M., Gendlina, I., Collins, C.M., and Acharya, K.A. (2004) Crystal structure of a dimeric form of Streptococcal pyrogenic exotoxin A (SpeA1), Prot. Science 13: 2285-90.
Gendlina, I., Gutman, D. M., Thomas, V. J., and Collins, C. M. (2002) Urea-dependent signal transduction by the virulence regulator UreR. J. Biol. Chem. 277:37349-37358.
Baker, M., Gutman, D. M., Papageorgiou, A. C., Collins, C. M., and Acharya, K. R. (2001) Structural features of a zinc binding site in the superantigen Streptococcal pyrogenic exotoxin A (SpeA1): implications for MHC class II recognition. Prot. Science 10:1268-1273.
Plano, L. R. W., Adkins, B., Woischnik, M., Ewing, R., Collins, C. M. (2001) Toxin levels in serum correlate with the development of staphylococcal scalded skin syndrome. Infect. Immun. 69:5193-5197.
Plano, L. R. W., Gutman, D. M., Woischnik, M., and Collins, C. M. (2000) Recombinant Staphylococcus aureus Exfoliative Toxins are not Bacterial Superantigens. Infec. Immun. 68:3048-3052.
Papageorgiou, A. C., Plano, L. R. W., Collins, C. M., Acharya, K. R. (2000) Structural differences in Staphylococcus aureus exfoliative toxins A and B as revealed from their crystal structures. Prot. Science 9:610-618.
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