Heat-Resistant Agglutinin 1 Is an Accessory Enteroaggregative<i>Escherichia coli</i>Colonization Factor

Diarrhea is a leading cause of illness and death, particularly in developing countries. Enteropathogenic Escherichia coli, enterotoxigenic E. coli (ETEC), enteroinvasive E. coli, enterohemorrhaghic E. coli (EHEC), enteroaggregative E. coli (EAEC) and diffusely adherent E. coli (DAEC) have been associated with diarrheal disease in different parts of Africa, particularly among young children, HIV-positive individuals, and visitors from abroad. Each of these E. coli pathotypes uses distinct mechanisms, which are only partially understood, to colonize infected hosts and produce diarrhea. All known diarrheagenic E. coli pathotypes have been reported from diverse locations within Africa but the true burden from these pathogens is unknown because very few studies seeking these organisms with discriminatory methodology have been performed. Recent reports implicate ETEC and EAEC in a considerable proportion of childhood and travellers' diarrheas and suggest that some sub-types of these categories may have greater epidemiological significance than others. The significant contribution of EHEC to bloody diarrhea and hemolytic uremic syndrome is underappreciated because diagnostic capacity for this pathotype is generally inferior to that for confounders such as Shigella and Entamoeba. Recent studies in Africa have revealed the worrisome emergence of antimicrobial resistance and high asymptomatic carriage rates for diarrheagenic E. coli but bacterial and host factors that predispose to disease, as well as non-human reservoirs, are largely unknown. Future diarrheal disease research needs to focus on broadening the repertoire of pathogens sought in epidemiological surveys to include multiple categories of diarrheagenic E. coli while building capacity to detect these pathogens in local reference laboratories.

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“…Recent research is beginning to uncover chromosomal loci with promise as epidemiological and virulence markers [217][218][219][220][221].…”

Section: Enteroaggregative E Colimentioning

confidence: 99%

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

Okeke

2009

J Infect Dev Ctries

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125

103

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“…To date, most studies of EAEC adherence have focused on structural adhesins known as aggregative adherence fimbriae. However, recent research has shown that EAEC strains also harbor an expanding repertoire of nonstructural outer membrane proteins that contribute to colonization (1,4,14,28).One such outer membrane protein is heat-resistant agglutinin 1 (Hra1), an accessory adhesin that we recently characterized in EAEC strain 042 (1). The hra1 gene (along with its 90% identical allelic variant hek, reported from uropathogenic E. coli and neonatal meningitic E. coli [11,39]) is predicted to encode a 29-kDa precursor, which is processed to a 25-kDa outer membrane protein.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…One such outer membrane protein is heat-resistant agglutinin 1 (Hra1), an accessory adhesin that we recently characterized in EAEC strain 042 (1). The hra1 gene (along with its 90% identical allelic variant hek, reported from uropathogenic E. coli and neonatal meningitic E. coli [11,39]) is predicted to encode a 29-kDa precursor, which is processed to a 25-kDa outer membrane protein.…”

mentioning

confidence: 99%

“…The hra1 gene (along with its 90% identical allelic variant hek, reported from uropathogenic E. coli and neonatal meningitic E. coli [11,39]) is predicted to encode a 29-kDa precursor, which is processed to a 25-kDa outer membrane protein. The 792-bp hra1 gene is sufficient to confer agglutination of human erythrocytes, bacterial autoaggregation, enhanced biofilm formation, and aggregative adherence to cultured HEp-2 cells (1,25). Hra1 shares 67% identity with the previously characterized outer membrane invasin and adhesin Tia (12,13).…”

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confidence: 99%

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The Heat-Resistant Agglutinin Family Includes a Novel Adhesin from Enteroaggregative Escherichia coli Strain 60A

et al. 2011

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Heat-resistant agglutinin 1 (Hra1) is an accessory colonization factor of enteroaggregative Escherichia coli (EAEC) strain 042. Tia, a close homolog of Hra1, is an invasin and adhesin that has been described in enterotoxigenic E. coli. We devised a PCR-restriction fragment length polymorphism screen for the associated genes and found that they occur among 55 (36.7%) of the enteroaggregative E. coli isolates screened, as well as lower proportions of enterotoxigenic, enteropathogenic, enterohemorrhagic, and commensal E. coli isolates. Overall, 25%, 8%, and 3% of 150 EAEC strains harbored hra1 alone, tia alone, or both genes, respectively. One EAEC isolate, 60A, produced an amplicon with a unique restriction profile, distinct from those of hra1 and tia. We cloned and sequenced the full-length agglutinin gene from strain 60A and have designated it hra2. The hra2 gene was not detected in any of 257 diarrheagenic E. coli isolates in our collection but is present in the genome of Salmonella enterica serovar Heidelberg strain SL476. The cloned hra2 gene from strain 60A, which encodes a predicted amino acid sequence that is 64% identical to that of Hra1 and 68% identical to that of Tia, was sufficient to confer adherence on E. coli K-12. We constructed an hra2 deletion mutant of EAEC strain 60A. The mutant was deficient in adherence but not autoaggregation or invasion, pointing to a functional distinction from the autoagglutinin Hra1 and the Tia invasin. Hra1, Tia, and the novel accessory adhesin Hra2 are members of a family of integral outer membrane proteins that confer different colonization-associated phenotypes.Enteroaggregative Escherichia coli (EAEC) strains are increasingly implicated in human diarrhea, especially among children living in developing countries (18,33). EAEC strains are exceptional colonizers and are defined by a characteristic stacked-brick adherence pattern (43). This aggregative pattern of adherence is a convergent phenotype produced in different lineages by a variety of adhesins, only some of which have been described (35). To date, most studies of EAEC adherence have focused on structural adhesins known as aggregative adherence fimbriae. However, recent research has shown that EAEC strains also harbor an expanding repertoire of nonstructural outer membrane proteins that contribute to colonization (1,4,14,28).One such outer membrane protein is heat-resistant agglutinin 1 (Hra1), an accessory adhesin that we recently characterized in EAEC strain 042 (1). The hra1 gene (along with its 90% identical allelic variant hek, reported from uropathogenic E. coli and neonatal meningitic E. coli [11,39]) is predicted to encode a 29-kDa precursor, which is processed to a 25-kDa outer membrane protein. The 792-bp hra1 gene is sufficient to confer agglutination of human erythrocytes, bacterial autoaggregation, enhanced biofilm formation, and aggregative adherence to cultured HEp-2 cells (1, 25). Hra1 shares 67% identity with the previously characterized outer membrane invasin and adhesin Tia (12, 13). The tia...

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Enteroaggregative Escherichia coli (EAEC)

Elias

Navarro-Garcı́a

2016

Escherichia Coli in the Americas

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Heat-Resistant Agglutinin 1 Is an Accessory EnteroaggregativeEscherichia coliColonization Factor

Cited by 39 publications

References 55 publications

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

The Heat-Resistant Agglutinin Family Includes a Novel Adhesin from Enteroaggregative Escherichia coli Strain 60A

Enteroaggregative Escherichia coli (EAEC)

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