Evolution and Sequence Diversity of FhuA in Salmonella and Escherichia

• Published in: Infection and immunity 2018-11, Vol.86 (11)
• Main Authors: Wang, Yejun, Chen, Xiongbin, Hu, Yueming, Zhu, Guoqiang, White, Aaron P, Köster, Wolfgang
• Format: Article
• Language: English
• Subjects: Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - genetics; Cluster Analysis; Escherichia - genetics; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Evolution, Molecular; Genetic Variation; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - genetics; Models, Molecular; Molecular Genomics; Phylogeny; Receptors, Virus - chemistry; Receptors, Virus - genetics; Salmonella - genetics; Sequence Analysis, DNA; Sequence Homology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00573-18

The operon, present in a number of , encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as a transporter for physiologically important chelated ferric iron but also as a receptor for various bacteriophages, toxins, and antibiotics, which are pathogenic to bacterial cells. In this research, gene distribution and sequence diversity were investigated in , especially and Comparative sequence analysis resulted in a phylogenetic tree that did not match the expected phylogeny of species or trees of the genes. The sequences showed a unique mosaic clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins in and , among which typical peptide fragment variations could be defined. Six fragmental insertions/deletions and two substitution fragments were discovered, for which the combination of polymorphism patterns could well classify the different clusters. Structural modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops present as part of the FhuA external pocket. These frequently mutated regions are likely under high selection pressure, with bacterial strains balancing escape from phage infection or toxin/antibiotics attack via gene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusual clustering suggests that high-frequency exchange of genes has occurred between enterobacterial strains after distinctive species were established.