Roles of iron acquisition systems in virulence of extraintestinal pathogenic Escherichia coli: salmochelin and aerobactin contribute more to virulence than heme in a chicken infection model

Abstract

BackgroundAvian pathogenic Escherichia coli (APEC) and uropathogenic E. coli (UPEC) are the two main subsets of extraintestinal pathogenic E. coli (ExPEC). Both types have multiple iron acquisition systems, including heme and siderophores. Although iron transport systems involved in the pathogenesis of APEC or UPEC have been documented individually in corresponding animal models, the contribution of these systems during simultaneous APEC and UPEC infection is not well described. To determine the contribution of each individual iron acquisition system to the virulence of APEC and UPEC, isogenic mutants affecting iron uptake in APEC E058 and UPEC U17 were constructed and compared in a chicken challenge model.ResultsSalmochelin-defective mutants E058ΔiroD and U17ΔiroD showed significantly decreased pathogenicity compared to the wild-type strains. Aerobactin defective mutants E058ΔiucD and U17ΔiucD demonstrated reduced colonization in several internal organs, whereas the heme defective mutants E058ΔchuT and U17ΔchuT colonized internal organs to the same extent as their wild-type strains. The triple mutant ΔchuTΔiroDΔiucD in both E058 and U17 showed decreased pathogenicity compared to each of the single mutants. The histopathological lesions in visceral organs of birds challenged with the wild-type strains were more severe than those from birds challenged with ΔiroD, ΔiucD or the triple mutants. Conversely, chickens inoculated with the ΔchuT mutants had lesions comparable to those in chickens inoculated with the wild-type strains. However, no significant differences were observed between the mutants and the wild-type strains in resistance to serum, cellular invasion and intracellular survival in HD-11, and growth in iron-rich or iron-restricted medium.ConclusionsResults indicated that APEC and UPEC utilize similar iron acquisition mechanisms in chickens. Both salmochelin and aerobactin systems appeared to be important in APEC and UPEC virulence, while salmochelin contributed more to the virulence. Heme bounded by ChuT in the periplasm appeared to be redundant in this model, indicating that other periplasmic binding proteins likely contributed to the observed no phenotype for the heme uptake mutant. No differences were observed between the mutants and their wild-type parents in other phenotypic traits, suggesting that other virulence mechanisms compensate for the effect of the mutations.

Zoonotic Potential of Escherichia coli Isolates from Retail Chicken Meat Products and Eggs

“…However, the larger haloes around some colonies, particularly the ExPEC isolates, are consistent with the known ability of ExPEC to produce other siderophores, such as aerobactin, salmochelin, and yersiniabactin (48,49), and this is supported here by the positive correlation between CAS agar halo diameter and the siderophore receptor genes iutA and iroN. The role of siderophores in the virulence of ExPEC is well established, as exemplified by a recent study that showed the importance of aerobactin and salmochelin in the virulence of both APEC and UPEC in a chicken model (50). Future studies should assess whether these ExPEC-associated iron uptake systems also promote bacterial persistence on poultry products, especially meat.…”

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

“…The role of aerobactin in the virulence of ExPEC is well documented for UPEC and avian-pathogenic E. coli (APEC) strains. Indeed, aerobactin is involved in the virulence of APEC strains 7122 and E058, as different iuc mutants presented decreased colonization of several organs during systemic infection of poultry (45,46,50,51). An iucD mutant of the UPEC strain U17 was also attenuated in a chicken model of colibacillosis (45).…”

“…Indeed, aerobactin is involved in the virulence of APEC strains 7122 and E058, as different iuc mutants presented decreased colonization of several organs during systemic infection of poultry (45,46,50,51). An iucD mutant of the UPEC strain U17 was also attenuated in a chicken model of colibacillosis (45). In a murine model of infection, a mutant of the UPEC strain CFT073 deficient in enterobactin and aerobactin production was also attenuated in the colonization of bladders and kidneys (48).…”

“…Salmochelins are glycosylated molecules of enterobactin that are synthesized by the iroBCDE gene products, while aerobactin is synthesized by the iucABCD gene products (39)(40)(41)(42). Interestingly, it has been reported that salmochelins and aerobactin are often associated with ExPEC strains and contribute to their virulence (38,(43)(44)(45)(46)(47)(48)(49)(50)(51).…”

The Transfer-Messenger RNA-Small Protein B System Plays a Role in Avian Pathogenic Escherichia coli Pathogenicity

“…coli has developed complex mechanisms to survive and proliferate inside the host (47)(48)(49)(50). APEC must escape a multitude of host defense mechanisms in order to cause septicemia.…”