Fig. 1.
Schematic representation of EAEC virulence factors.
Most EAEC virulence factors are regulated by the AggR transcriptional activator encoded on the plasmid of aggregative adherence (pAA). EAEC strains adhere in a “brick stacking” pattern and spread in intestinal epithelial cells via aggregative adherence fimbria (AAF). This AAF presents at least five antigenic variants regulated by the AggR master regulator. The AggR transcription factor also activates the genes that encode the anti-aggregation protein (Aap, dispersin) and its anti-aggregation transporter (Aat), and the type VI secretion system (T6SS). EAEC strains can form robust biofilms, which promote high resistance to desiccation, starvation, and host immune response. EAEC secretes at least three toxins: E. coli heat-stable enterotoxin (EAST-1), plasmid-encoded toxin, (Pet), and protein involved in colonization (Pic, with mucinase activity), which are not controlled by the AggR regulator, causing an increase in chloride secretion that correlates with secretory diarrhea.
Fig. 2.
Regulatory model of AggR and Aar on the EAEC virulence genes.
AggR master regulator activates the virulence regulon that includes: Aar regulatory protein, aggregative adherence fimbriae II (AAF/II), Type VI secretion system (T6SS), anti-aggregation protein (Aap, dispersin), and anti-aggregation transporter (Aat). Aar directly binds AggR, blocking its transcription activity. In addition, Aar forms multiprotein complexes together with H-NS, altering the repressor function of nucleoid protein on its promoter.
Table I
Virulence genes regulated by AggR*.
| Location | Virulence factor | Regulated genes | Description |
|---|---|---|---|
| pAA2 plasmid | AAF/II | aafA, aafB, aafC, aafD | major subunit, minor subunit, usher protein, chaperone of AAF/II |
| dispersin | aap | dispersin (antiaggregation protein) | |
| dispersin export apparatus | aatA, aatB, aatC, aatD, aatP | TolC-like outer membrane protein, hypothetic protein, ABC transporter, N-acyltransferase, permease protein | |
| AggR | aggR | AraC/XylS-type transcriptional regulator | |
| Aar | aar | ANR-family regulator | |
| ORF3 | EC042_RS26240 (pAA003) | isoprenyl diphosphate synthase | |
| Idi (ORF4) | idi | isopentenyl-diphosphate delta-isomerase | |
| Shf | shf | polysaccharide deacetylase | |
| EC042_RS30880 (pAA005A), EC042_RS26330 (pAA0020), (pAA0047), (pAA0056) | hypothetical proteins | ||
| Chromosome | Type VI secretion system | aaiA-U (EC042_RS24360–EC042_RS24465) | T6SS putative proteins |
| EC042_RS16995 (EC042_3181) | putative transcriptional regulator | ||
| EC042_RS17000 (EC042_3182) | ParB-type nuclease | ||
| EC042_RS17030 (EC042_3187) | putative helicase | ||
| EC042_RS17005, EC042_RS17010, EC042_RS21290 (EC042_3183, EC042_3184, EC042_4006) | hypothetic proteins |