Dataset Information

Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections.

ABSTRACT: Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and an infection threat and orchestrate a series of host-protective responses. Several studies have investigated the antimicrobial role of hepcidin, but the results have been controversial. Here, we aimed to examine the role of hepcidin in bacterial adherence and invasion in vitro We found that porcine hepcidin could decrease the amount of the extracellular pathogen enterotoxigenic Escherichia coli (ETEC) K88 that adhered to cells because it caused the aggregation of the bacteria. However, addition of hepcidin to macrophages infected with the intracellular pathogen Salmonella enterica serovar Typhimurium enhanced the intracellular growth of the pathogen through the degradation of ferroportin, an iron export protein, and then the sequestration of intracellular iron. Intracellular iron was unavailable by use of the iron chelator deferiprone (DFO), which reduced intracellular bacterial growth. These results demonstrate that hepcidin exhibits different functions in extracellular and intracellular bacterial infections, which suggests that different defense strategies should be taken to prevent bacterial infection.

SUBMITTER: Liu D

PROVIDER: S-EPMC5610511 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections.

Liu Dan D Gan Zhen-Shun ZS Ma Wan W Xiong Hai-Tao HT Li Yun-Qing YQ Wang Yi-Zhen YZ Du Hua-Hua HH

Antimicrobial agents and chemotherapy 20170922 10

Hepcidin, an antimicrobial peptide, was discovered to integrate diverse signals from iron status and an infection threat and orchestrate a series of host-protective responses. Several studies have investigated the antimicrobial role of hepcidin, but the results have been controversial. Here, we aimed to examine the role of hepcidin in bacterial adherence and invasion <i>in vitro</i> We found that porcine hepcidin could decrease the amount of the extracellular pathogen enterotoxigenic <i>Escheric ...[more]

PMID: 28760901

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Project description:Salmonella and Escherichia coli mannose-binding type 1 fimbriae exhibit highly similar receptor specificities, morphologies, and mechanisms of assembly but are nonorthologous in nature, i.e., not closely related evolutionarily. Their operons differ in chromosomal location, gene arrangement, and regulatory components. In the current study, we performed a comparative genetic and structural analysis of the major structural subunit, FimA, from Salmonella and E. coli and found that FimA pilins undergo diverse evolutionary adaptation in the different species. Whereas the E. coli fimA locus is characterized by high allelic diversity, frequent intragenic recombination, and horizontal movement, Salmonella fimA shows structural diversity that is more than 5-fold lower without strong evidence of gene shuffling or homologous recombination. In contrast to Salmonella FimA, the amino acid substitutions in the E. coli pilin heavily target the protein regions that are predicted to be exposed on the external surface of fimbriae. Altogether, our results suggest that E. coli, but not Salmonella, type 1 fimbriae display a high level of structural diversity consistent with a strong selection for antigenic variation under immune pressure. Thus, type 1 fimbriae in these closely related bacterial species appear to function in distinctly different physiological environments. E. coli and Salmonella are enteric bacteria that are closely related from an evolutionary perspective. They are both notorious human pathogens, though with somewhat distinct ecologies and virulence mechanisms. Type 1 fimbriae are rod-shaped surface appendages found in most E. coli and Salmonella isolates. In both species, they mediate bacterial adhesion to mannose receptors on host cells and share essentially the same morphology and assembly mechanisms. Here we show that despite the strong resemblances in function and structure, they are exposed to very different natural selection environments. Sequence analysis indicates that E. coli, but not Salmonella, fimbriae are subjected to strong immune pressure, resulting in a high level of major fimbrial protein gene shuffling and interbacterial transfer. Thus, evolutionary analysis tools can provide evidence of divergent physiological roles of functionally similar traits in different bacterial species.

Dataset Information

Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections.

Publications

Synthetic Porcine Hepcidin Exhibits Different Roles in Escherichia coli and Salmonella Infections.

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