The Export of Coat Protein from Enteroaggregative Escherichia coli by a Specific ATP-binding Cassette Transporter System

Abstract

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen characterized by aggregative adherence (AA) to cultured human mucosal epithelium cells. We have recently characterized a 10.2-kDa protein, called dispersin, which is exported from the bacteria and which promotes dispersal of EAEC across the intestinal mucosa. Here, we present evidence that dispersin is exported by a putative ABC transporter complex, which is encoded by a genetic locus of the EAEC virulence plasmid pAA2. We demonstrate that the locus comprises a cluster of five genes (designated aat-PABCD), including homologs of an inner-membrane permease (AatP), an ATP-binding cassette protein (AatC) and the outer membrane protein TolC (AatA). We show that, like TolC, AatA localizes to the outer membrane independently of its ABC partner. Dispersin appears to require the Aat complex for outer membrane translocation but not for secretion across the inner membrane. We also show that, like the dispersin gene, transcription of the aat cluster is dependent on AggR, a regulator of virulence genes in EAEC. We propose that the aat cluster encodes a specialized ABC transporter, which plays a role in the pathogenesis of EAEC by transporting dispersin out of the bacterial cell.

Mecanismos de virulencia de Escherichia coli enteropatógena

“…En la colonización bacteriana actúa un complejo denominado Aat que se requiere para el transporte de una dispersina codificada por el gen aap, juntos regulados por AggR y codificados en el plásmi-do pAA. Aat media la secreción de la dispersina desde la membrana externa de la bacteria para promover la colonización de la mucosa intestinal (Figura 4a) 94,95 .…”

Seroprevalence of the enteroaggregative Escherichia coli virulence factor dispersin among USA travellers to Cuernavaca, Mexico: a pilot study

“…This gene lies immediately upstream of aggR, the gene encoding a master regulator of a myriad of plasmid genes, including aap and chromosomal genes that express virulence factors. Dispersin requires an ATP-binding cassette complex transporter, encoded by the gene aatA, for outer-membrane translocation where it non-covalently attaches to the surface of the bacterium (Sheikh et al, 2002;Nishi et al, 2003).…”

“…Dispersin is a 10.2 kDa protein that is responsible for dispersing EAEC along intestinal epithelium and facilitating penetration of mucus along the intestinal mucosa (Sheikh et al, 2002;Nishi et al, 2003;Nataro, 2005). In one laboratory, 80 % of EAEC isolates were identified as carrying the aap gene encoding dispersin (Sheikh et al, 2002).…”

Detection of enteroaggregative Escherichia coli in faecal samples from patients in the community with diarrhoea

“…Certain strains carry a high-molecular-weight plasmid (pAA) associated with AA (Vial et al, 1988;Law & Chart, 1998), on which a number of virulence genes are located, including an antiaggregation protein transporter gene (aat; previously referred to as CVD432 or the AA probe) (Baudry et al, 1990;Nishi et al, 2003) and an enteroaggregative heat stable toxin (EAST) gene (astA) (Savarino et al, 1991;Menard & Dubreuril 2002). Located on the chromosome, on the pheU pathogenicity island, are the gene clusters SciI and SciII.…”