Abstract

The ultimate goal of our studies is to understand in molecular terms how bacteria cause diseases. A bacterial infection can be regarded as a war between the microbe and the host where the bacteria's attempt to adhere to and colonize the host tissue represent the first battle in the campaign. For our model organism, Staphylococcus aureus tissue adherence is mediated by a sub-family of bacterial surface adhesins called MSCRAMMs. In previous work, we discovered the MSCRAMMs, cloned and sequenced several MSCRAMM genes and began characterizing the encoded proteins and their interactions with host components. These studies revealed amazingly sophistical mechanisms of host tissue adherence designed to avoid inactivation by host defense systems. We hypothesize that the MSCRAMMs are in the first line of bacterial attachment and their molecular design makes them uniquely suited for this role. Consequently, we now propose a detailed molecular analysis of Staphylococcal surface proteins and their interactions with host components.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI020624-17
Application #
6127084
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1989-12-01
Project End
2005-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
17
Fiscal Year
2000
Total Cost
$426,035
Indirect Cost

  Institution

Name
Texas A&M University
Department
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845

  Publications

Casillas-Ituarte, Nadia N; Cruz, Carlos H B; Lins, Roberto D et al. (2017) Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin-binding protein A affect bond strength and fibronectin conformation. J Biol Chem 292:8797-8810
Garcia, Brandon L; Zhi, Hui; Wager, Beau et al. (2016) Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex. PLoS Pathog 12:e1005404
Arora, Srishtee; Uhlemann, Anne-Catrin; Lowy, Franklin D et al. (2016) A Novel MSCRAMM Subfamily in Coagulase Negative Staphylococcal Species. Front Microbiol 7:540
Ganesh, Vannakambadi K; Liang, Xiaowen; Geoghegan, Joan A et al. (2016) Lessons from the Crystal Structure of the S. aureus Surface Protein Clumping Factor A in Complex With Tefibazumab, an Inhibiting Monoclonal Antibody. EBioMedicine 13:328-338
Liang, Xiaowen; Garcia, Brandon L; Visai, Livia et al. (2016) Allosteric Regulation of Fibronectin/?5?1 Interaction by Fibronectin-Binding MSCRAMMs. PLoS One 11:e0159118
Kuipers, Annemarie; Stapels, Daphne A C; Weerwind, Lleroy T et al. (2016) The Staphylococcus aureus polysaccharide capsule and Efb-dependent fibrinogen shield act in concert to protect against phagocytosis. Microbiology 162:1185-94
Ko, Ya-Ping; Kang, Mingsong; Ganesh, Vannakambadi K et al. (2016) Coagulase and Efb of Staphylococcus aureus Have a Common Fibrinogen Binding Motif. MBio 7:e01885-15
Prasad, Joni M; Gorkun, Oleg V; Raghu, Harini et al. (2015) Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense. Blood 126:2047-58
Somarajan, Sudha R; La Rosa, Sabina Leanti; Singh, Kavindra V et al. (2015) The fibronectin-binding protein Fnm contributes to adherence to extracellular matrix components and virulence of Enterococcus faecium. Infect Immun 83:4653-61
Galloway-Peña, Jessica R; Liang, Xiaowen; Singh, Kavindra V et al. (2015) The identification and functional characterization of WxL proteins from Enterococcus faecium reveal surface proteins involved in extracellular matrix interactions. J Bacteriol 197:882-92

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