Extraintestinal pathogenic Escherichia coli (ExPEC) refers to a group of strains capable of causing diseases outside the intestinal tract, including uropathogenic E. coli (UPEC), sepsis-associated E. coli, and neonatal meningitis-associated E. coli. Among ExPEC strains, UPEC is the most common cause of human urinary tract infections (UTIs)
[2, 3]. Avian pathogenic E. coli (APEC) is the main cause of avian colibacillosis, which refers to any localized or systemic infections such as acute fatal septicemia or subacute pericarditis and airsacculitis. APEC and UPEC possess similar virulence factors for colonizing and invading the host, including adhesins, toxins, polysaccharide coatings, protectins, invasins, and iron acquisition systems
Iron is an essential element for survival of E. coli. It facilitates numerous cellular activities, such as peroxide reduction, electron transport, and nucleotide biosynthesis
[6–9]. As iron exists at low concentrations in extraintestinal sites of infection, the ExPEC strains have evolved multiple strategies for sequestering iron from the host.
The direct way is to take up iron from either free heme or from heme-containing proteins, such as hemoglobin or hemopexin. Heme is the most abundant iron source in vivo, and the presence of a heme system in ExPEC strains may be important for the acquisition of iron from heme or hemoglobin. Specific outer membrane receptors Hma and ChuA bind host hemoproteins and transfer the coordinated heme molecule into the periplasm, where an ABC transport system delivers it to the cytoplasm. Once taken up by ChuA and transported across the outer membrane, heme is internalized into the periplasm and then bound by heme-specific periplasmic transport protein ChuT, which mediates heme transfer to the cytoplasm through an ATP-binding cassette (ABC) transporter
The indirect strategy for iron acquisition is based on a shuttle mechanism, which uses small-molecule compounds called siderophores as high-affinity ferric iron chelators
, including the catecholates enterobactin, salmochelin, the hydroxamate aerobactin, and yersiniabactin
. Salmochelin molecules were first discovered in Salmonella enterica. The iroA locus responsible for salmochelin production was also first identified in Salmonella spp.
. Salmochelins are C-glucosylated derivatives of enterobactin, encoded by the iroBCDEN gene cluster
. Among E. coli isolates, iro sequences have been described in ExPEC strains isolated from patients with neonatal meningitis
, UTIs, and prostatitis in humans
[17, 18], as well as from APEC isolates from poultry. Compared to enterobactins, salmochelins are superior siderophores in the presence of serum albumin, which may suggest that salmochelins are considerably more important in the pathogenesis of certain E. coli and Salmonella infections than enterobactins
. In ExPEC strains, the gene cluster responsible for salmochelin biosynthesis and transport is generally found on ColV or ColBM virulence plasmids, and has also been identified on chromosomal pathogenicity-associated islands (PAI) in some strains
. The salmochelin gene cluster contains a gene encoding a cytoplasmic esterase, IroD. IroD can hydrolyze the ester bonds of both enterobactin and salmochelin molecules, which is required for subsequent iron release from salmochelin
Aerobactin is a hydroxamate siderophore produced by most APEC strains and other pathogenic E. coli. It is synthesized by the iucABCD-encoded gene products and taken up by the iutA-encoded receptor protein
[23–25]. Despite the chemical differences among these distinct siderophores, each system is comprised of components mediating the specific steps required for ferric iron uptake, including siderophore synthesis in the cytoplasm, secretion, reception of the ferri-siderophore at the outer membrane surface, internalization, and iron release in the cytoplasm
While both APEC and UPEC strains have multiple iron acquisition systems, the role of distinct iron uptake systems in the pathogenesis of both APEC and UPEC has not been illustrated in the same chicken challenge model. In this study, the genes chuT, iroD and iucD were chosen to assert the roles of heme, salmochelin and aerobactin in the virulence of APEC E058 and UPEC U17.