The metal cofactors are essential for the function of many enzymes. The host restricts the metal acquisition of pathogens for
their immunity and the pathogens have evolved many ways to obtain metal ions for their survival and growth. Salmonella
enterica serovar Typhimurium also needs several metal cofactors for its survival, and manganese has been found to contribute
to Salmonella pathogenesis. Manganese helps Salmonella withstand oxidative and nitrosative stresses. In addition,
manganese affects glycolysis and the reductive TCA, which leads to the inhibition of energetic and biosynthetic metabolism.
Therefore, manganese homeostasis is crucial for full virulence of Salmonella. Here, we summarize the current information
about three importers and two exporters of manganese that have been identified in Salmonella. MntH, SitABCD, and ZupT
have been shown to participate in manganese uptake. mntH and sitABCD are upregulated by low manganese concentration,
oxidative stress, and host NRAMP1 level. mntH also contains a Mn2+-
dependent riboswitch in its 5′ UTR. Regulation of
zupT expression requires further investigation. MntP and YiiP have been identified as manganese efflux proteins. mntP is
transcr!ptionally activated by MntR at high manganese levels and repressed its activity by MntS at low manganese levels.
Regulation of yiiP requires further analysis, but it has been shown that yiiP expression is not dependent on MntS. Besides
these five transporters, there might be additional transporters that need to be identified.
Escherichia coli (E. coli) infection is very common among
young growing animals, and zinc supplementation is often
used to alleviate inflammation induced by this disease. Therefore,
the objective of this study was to evaluate whether chitosan-
chelated zinc (CS-Zn) supplementation could attenuate
gut injury induced by E. coli challenge and to explore how CSZn
modulates cecal microbiota and alleviates intestinal inflammation
in weaned rats challenged with E. coli. 36 weaned
rats (55.65 ± 2.18 g of BW, n = 12) were divided into three
treatment groups consisting of unchallenged rats fed a basal
diet (Control) and two groups of rats challenged with E. coli
and fed a basal diet or a diet containing 640 mg/kg CS-Zn
(E. coli + CS-Zn, containing 50 mg/kg Zn) for a 14-day experiment.
On days 10 to 12, each rat was given 4 ml of E. coli
solution with a total bacteria count of 1010 CFU by oral gavage
daily or normal saline of equal dosage. CS-Zn supplementation
mitigated intestinal morphology impairment (e.g.
higher crypt depth and lower macroscopic damage index)
induced by E. coli challenge (P < 0.05), and alleviated the increase
of Myeloperoxidase (MPO) activity after E. coli challenge
(P < 0.05). 16S rRNA sequencing analyses revealed that
E. coli challenge significantly increased the abundance of Verrucomicrobia
and E. coli (P < 0.05). However, CS-Zn supplementation
increased the abundance of Lactobacillus and decreased
the relative abundance of Proteobacteria, Desulfovibrio
and E. coli (P < 0.05). The concentrations of butyrate in
the cecal digesta, which decreased due to the challenge, were
higher in the E. coli + CS-Zn group (P < 0.05). In addition,
CS-Zn supplementation significantly prevented the elevation
of pro-inflammatory cytokines IL-6 concentration and upregulated
the level of anti-inflammatory cytokines IL-10 in
cecal mucosa induced by E. coli infection (P < 0.05). In conclusion,
these results indicate that CS-Zn produces beneficial
effects in alleviating gut mucosal injury of E. coli challenged
rats by enhancing the intestinal morphology and modulating
cecal bacterial composition, as well as attenuating inflammatory
response.