Iron is an essential nutrient for bacterial growth. Therefore, bacteria have evolved chelation mechanisms to acquire
iron for their survival.
Enterobactin, a
chelator with high affinity for ferric
iron, is secreted by Escherichia coli and contributes to its improved bacterial fitness. In this preliminary study, we evaluated
enterobactin deficiency both in vitro and in vivo in the context of E. coli
mastitis. Firstly, we showed that expression of
lipocalin 2, a
protein produced by the host that is able to both bind and deplete
enterobactin, is increased upon E. coli
infection in the cow's mastitic mammary gland. Secondly, we demonstrated in vitro that
enterobactin deficiency does not alter
interleukin (IL)-8 expression in bovine mammary epithelial cells and its associated neutrophil recruitment. However, a significantly increased
reactive oxygen species production of these neutrophils was observed. Thirdly, we showed there was no significant difference in bacterial in vitro growth between the
enterobactin-deficient mutant and its wild-type counterpart. However, when further explored in a murine model for
bovine mastitis, the
enterobactin-deficient mutant vs. the wild-type strain revealed a significant reduction of the bacterial load and, consequently, a decrease in pro-inflammatory
cytokines (IL-1α,-1β,-4,-6, and-8). A reduced neutrophilic influx was also observed immunohistochemically. These findings therefore identify interference of the
enterobactin iron-scavenging mechanism as a potential measure to decrease the fitness of E. coli in the mastitic mammary gland.