Long Polar Fimbriae of Attaching and Effacing Escherichia coli
Principal Investigator: Alfredo Torres
Affiliation: University of Texas Medical Branch
Abstract: DESCRIPTION (provided by applicant): The expression of Attaching and Effacing Escherichia coli (AEEC) virulence factors is a tightly regulated process, and, in some cases, the identification of these factors has been difficult because they are either repressed in vitro or the conditions of expression are unknown. While it is evident that expression of certain virulence factors is strictly associated with human disease, the additional factors present in AEEC strains that are linked to their pathogenic process remain unclear. Lack of a full understanding of how the genes encoding these additional virulence factors are controlled is important, because, without this knowledge, we are unlikely to understand the overall pathogenic properties of AEEC strains. Thus, our objective is to determine how the Long Polar (LP) fimbriae in AEEC strains contribute to pathogenesis and to use these fimbrial-encoding genes as markers to detect virulent strains. The central hypothesis is that, in addition to the already characterized colonization factors (e.g., intimin-mediated adhesion), AEEC strains possess a highly regulated LP fimbriae, that plays a role in the colonization process, and although the genes encoding these fimbriae are widely distributed in pathogenic E. coli strains, some LP fimbriae types are found exclusively in specific AEEC strains. We will test this hypothesis through three specific aims, which are to: 1) Define whether Ler and H-NS act as a selective silencing/anti-silencing defense system that controls LP fimbriae expression in AEEC strains;2) Identify the regulatory protein(s) controlling LP fimbriae expression in atypical EPEC and determine in a rabbit model the function of LP fimbriae during colonization;and 3) Characterize the distribution of the LP fimbrial gene clusters among AEEC strains and determine whether certain LP fimbrial subunit types are reliable markers of different pathogenic AEEC strains. To accomplish our aims, we will fully characterize the functions of Ler, H-NS, and atypical enteropathogenic E. coli-encoded regulators under in vitro and in vivo (infant rabbit colonization model) conditions and perform a detailed study of prevalence of the lpf genes in specific subsets of pathogenic AEEC strains. Our research work is innovative because it capitalizes on our findings regarding novel colonization factors in AEEC strains and their potential application in therapeutics and diagnostics. The results from studies of the regulatory networks controlling LP fimbriae expression have significance, because we will be able to identify fundamental differences to explain the tissue tropism of different AEEC strains and to determine whether silencing of LP fimbriae is an example of a defense system that AEEC strains have against horizontally acquired genes. In addition, the use of the rabbit model will give us new insight into the pathogenesis and colonization properties of AEEC strains. An understanding of the mechanisms underlying AEEC colonization to the gastrointestinal tract will not only further our knowledge of the pathogenesis of these organisms but also provide opportunities for reducing infection rates and improving treatment options against these biological agents classified as category B pathogens due t their potential use as a food safety threat. PUBLIC HEALTH RELEVANCE: Attaching and effacing Escherichia coli (AEEC) represent a diverse group of isolates implicated in diarrhea in humans in several countries. Most AEEC strains possess highly regulated Long Polar (LP) fimbriae, which contribute to the intestinal colonization process of some of the AEEC isolates. Their full characterization will provide new and deeper insights into the process of AEEC colonization, and a better understanding of their regulatory mechanisms controlling expression, which will be a basis for developing novel therapeutics and simplified diagnostic tests
Funding Period: ----------------2009 - ---------------2014-
more information: NIH RePORT
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Centre for Agricultural Research, Institute for Veterinary Medical Research, Hungarian Academy of Sciences, Budapest, Hungary
Pathog Dis 68:1-7. 2013..Our data indicate that lpf2 loci are highly conserved in E. coli isolates; however, its role in adherence might be masked by other uncharacterized adhesins...
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Centro de Estudios Moleculares, Departamento de Pediatria, Facultad de Medicina, Universidad de Chile, Hospital Dr Luis Calvo Mackenna, Santiago, Chile
Vet Immunol Immunopathol 152:126-31. 2013..The analysis indicated that the NF-κB pathway is activated in response to Lpf-expressing STEC. Therefore, our study supports the role of Lpf as a STEC factor mediating intestinal inflammation...
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Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA
Front Cell Infect Microbiol 2:8. 2012..In conclusion, our mPCR methodology permitted differentiation of EPEC, STEC and EHEC strains from other pathogenic E. coli; therefore, the assay becomes an additional tool for rapid diagnosis of these organisms...
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Posgrado en Microbiología, Centro de Investigaciones en Ciencias Microbiológicas, B Universidad Autonoma de Puebla, Puebla, Mexico
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Departamento de Biologia, Facultad de Quimica y Biologia, Universidad de Santiago de Chile, Santiago, Chile
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Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
Gut Microbes 3:272-6. 2012..In this addendum article, we provide a continued perspective on the predicted roles of Lpf and curli, both in vivo and in vitro...
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Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
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Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
Infect Immun 80:914-20. 2012..In addition to suggesting that Lpf can contribute to EHEC intestinal colonization, our observations indicate that the regulatory pathways governing the expression of Lpf and curli are interdependent...
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Centro de Estudios Moleculares, Departamento de Pediatria, Hospital Dr Luis Calvo Mackenna, Facultad de Medicina, Universidad de Chile, Santiago, Chile
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Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
J Clin Microbiol 49:3334-7. 2011..coli (EPEC) strains of various serotypes. Although the most prevalent gene was lpfA in both groups, paa was the only potential diarrhea-associated gene in atypical EPEC...
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Centro de Estudios Moleculares, Departamento de Pediatria, Hospital Dr Luis Calvo Mackenna, Santiago, Chile
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Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 1070, USA
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Servicio Fisiopatogenia, Departamento de Bacteriologia, Instituto Nacional de Enfermedades Infecciosas ANLIS Dr Carlos G Malbran, Buenos Aires, Argentina
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