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Publication Abstract from PubMed

Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. Acute infection can be antecedent to highly debilitating long-term sequelae. Expression of iron acquisition systems is vital for C. jejuni to survive the low iron availability within the human gut. The C. jejuni fetMP-fetABCDEF gene cluster is known to be upregulated during human infection and under iron limitation. While FetM and FetP have been functionally linked to iron transport in prior work, here we assess the contribution by each of the downstream genes ( fetABCDEF ) to C. jejuni growth during both iron-depleted and iron-replete conditions. Significant growth impairment was observed upon disruption of fetA , fetB, fetC , and fetD , suggesting a role in iron acquisition for each encoded protein. FetA expression was modulated by iron-availability but not dependent on the presence of FetB, FetC, FetD, FetE or FetF. Functions of the putative thioredoxins FetE and FetF were redundant in iron scavenging, requiring a double deletion (Delta fetEF ) to exhibit a growth defect. C. jejuni FetE was expressed and the structure solved to 1.50 A, revealing structural similarity to thiol-disulfide oxidases. Functional characterization in biochemical assays showed that FetE reduced insulin at a slower rate than E. coli Trx and that together, FetEF promoted substrate oxidation in cell extracts, suggesting that FetE (and presumably FetF) are oxidoreductases that can mediate oxidation in vivo . This study advances our understanding of the contributions by the fetMP-fetABCDEF gene cluster to virulence at a genetic and functional level, providing foundational knowledge towards mitigating C. jejuni -related morbidity and mortality.

Dissecting components of the Campylobacter jejuni fetMP-fetABCDEF gene cluster in iron scavenging.,Richardson-Sanchez T, Chan ACK, Sabatino B, Lin H, Gaynor EC, Murphy MEP bioRxiv [Preprint]. 2023 Jul 5:2023.07.05.547857. doi: 10.1101/2023.07.05.547857. PMID:37461706^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.