2212. The Identification of a Novel Extracellular Metalloproteinase Produced by Clostridium sordellii
Session: Poster Abstract Session: Microbial Pathogenesis
Saturday, October 29, 2016
Room: Poster Hall
Background: Clostridium sordellii is a significant pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome and an extreme increase in circulating leukocytes, termed the leukemoid reaction (LR) are hallmark features of these infections. C. sordellii produces several virulence factors including phospholipase, neuraminidase (NanS), and two large clostridial glucosylating toxins, TcsL and TscH. Recently, our group demonstrated that C. sordellii produced a metalloproteinase that cleaved human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion critical to hematopoietic precursor retention and leukocyte diapedesis.

Methods: In the present study, we successfully identified the open reading frame encoding the metalloproteinase of C. sordellii (Mcs1) within the ATCC 9714 genome. Additionally, an Δmcs1mutant strain was developed using the ClosTron mutagenesis technique, and high-performance computing and high-dimensional data analytics was also used to corroborate the structure and function of the Mcs1 protease.

Results: No VCAM-1 proteolysis was identified from exotoxins collected from mutant strain cultures. Additionally, a recombinant form of the Mcs1 protease retained functional VCAM-1 cleavage activity. Computational analytics confirmed the protein-protein interaction between Mcs1 and VCAM-1 bound molecules.

Conclusion: This study represents the identification and characterization of a novel metalloproteinase that directly modifies adhesions critical to the retention of hematopoietic precursors to the bone marrow environment. Better understanding the role of Mcs1 in the development of LR and the pathogenesis of C. sordelliiinfection may lead to the development of novel diagnostic tools or therapeutic strategies that could limit the morbidity and mortality associated with this deadly infection.

Michael Aldape, PhD1, Dong Xu, PhD2, Eric Mcindoo, BS1, John French, BS1 and Dennis Stevens, MD, PhD1, (1)Infectious Diseases, Veterans Affairs Medical Center, Boise, ID, (2)Biological and Pharmaceutical Sciences, Idaho State University-Meridian Health Science Center, Meridian, ID

Disclosures:

M. Aldape, None

D. Xu, None

E. Mcindoo, None

J. French, None

D. Stevens, None

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