Abstract

Enteropathogenic (EPEC) and enterohemorrhagic E. coli (EHEC) are recognized as important ethiologic agents of intestinal disease world-wide. They are collctively called """"""""attaching and effacing E. coli (AEEC) because they cause dramatic intestinal lesions that lead to destruction of the gut epithelium. The interaction of the bacteria with host epithelial cells entails the participation of several adhesins. While the adhesins the mediate attachment of EPEC are apparently known (intimin, bundle-forming pilus, flagella and the EspA fiber), intimin is the only adhesin recognized in EHEC. The analysis of the genome sequence of E. coli K-12 and EHEC EDL933 reveals the presence of several putative fimbrial genes, for which their role in the virulence scheme of AEEC is largely unknown. This suggests that other yet uncharacterized adhesins must exist. We have discovered that AEEC strains produce host-cell inducible YagZ pili at 37oC, which are composed of 22 kDa-proteins encoded by the yagZ gene found in E. coli K-12 and EHEC EDL933. There is a clear indication that the expression of YagZ pili in AEEC is linked to a strict regulatory control, and perhaps to virulence gene regulation, which is overcome by the presence of epithelial cells. We hypothesize that YagZ pili are accessory adherence factors that contribute to the adhesive properties of AEEC. The central focus of this proposal lies in function-regulation-biogenesis studies that will address questions concerning the role of YagZ pili in adherence to epithelial cells, the complex regulatory interplay between YagR and the known virulence and global rergulators. The long-term objective of this project is provide the molecular bases to advance knowledge of AEEC mechanisms of adherence and pathogenesis, and to establish a ground for interesting strategies regarding immunoprophylaxis of animal and human infections caused by these important pathogens.
Specific Aim 1 : To define the role of YagZ pili in AEEC adhesion Specific Aim 2. To determine how YagZ pilus regulation occurs in AEEC Specific Aim 3. To determine how YagZ pili biogenesis occurs in AEEC

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI066012-06
Application #
7941706
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Baqar, Shahida
Project Start
2006-05-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2013-04-30
Support Year
6
Fiscal Year
2010
Total Cost
$284,130
Indirect Cost

  Institution

Name
University of Florida
Department
Genetics
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Saldaña, Zeus; De la Cruz, Miguel A; Carrillo-Casas, Erika Margarita et al. (2014) Production of the Escherichia coli common pilus by uropathogenic E. coli is associated with adherence to HeLa and HTB-4 cells and invasion of mouse bladder urothelium. PLoS One 9:e101200
Stacy, Alyssa K; Mitchell, Natalie M; Maddux, Jacob T et al. (2014) Evaluation of the prevalence and production of Escherichia coli common pilus among avian pathogenic E. coli and its role in virulence. PLoS One 9:e86565
Hernandes, Rodrigo T; De la Cruz, Miguel A; Yamamoto, Denise et al. (2013) Dissection of the role of pili and type 2 and 3 secretion systems in adherence and biofilm formation of an atypical enteropathogenic Escherichia coli strain. Infect Immun 81:3793-802
Alcantar-Curiel, Maria D; Blackburn, Dana; Saldana, Zeus et al. (2013) Multi-functional analysis of Klebsiella pneumoniae fimbrial types in adherence and biofilm formation. Virulence 4:129-38
Garnett, James A; Martinez-Santos, Veronica I; Saldana, Zeus et al. (2012) Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus. Proc Natl Acad Sci U S A 109:3950-5
Martínez-Santos, Verónica I; Medrano-López, Abraham; Saldaña, Zeus et al. (2012) Transcriptional regulation of the ecp operon by EcpR, IHF, and H-NS in attaching and effacing Escherichia coli. J Bacteriol 194:5020-33
Hernandes, Rodrigo T; Velsko, Irina; Sampaio, Suely C F et al. (2011) Fimbrial adhesins produced by atypical enteropathogenic Escherichia coli strains. Appl Environ Microbiol 77:8391-9
Avelino, Fabiola; Saldana, Zeus; Islam, Sohidul et al. (2010) The majority of enteroaggregative Escherichia coli strains produce the E. coli common pilus when adhering to cultured epithelial cells. Int J Med Microbiol 300:440-8
Ledesma, Maria A; Ochoa, Sara A; Cruz, Ariadnna et al. (2010) The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells. PLoS One 5:e12127
Xicohtencatl-Cortes, Juan; Saldaña, Zeus; Deng, Wanyin et al. (2010) Bacterial macroscopic rope-like fibers with cytopathic and adhesive properties. J Biol Chem 285:32336-42

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