What’s metal got to do with it? Transition metals in Clostridioides difficile infection

Gomez, Suzanna Y; Patel, Jay; Lopez, Christopher A.

doi:10.1016/j.mib.2021.11.004

Cited by 2 publications

(2 citation statements)

References 60 publications

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Section: Discussionmentioning

confidence: 99%

“…C. difficile modulates internal and surrounding metal pools using a variety of mechanisms including the Feo transporters, a heme efflux pump (HatT), a heme sequestering protein (HsmA), and transporters for other metals (ZupT -zinc, OppA -nickel) (44). Herein, we present an additional mechanism using the transporter FhuDBGC to acquire the siderophore Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) analysis of the intergenic regions of fhuDBGC + MATE was performed using primer sets (1-6) described in Table S2 to detect mRNA at the regions indicated.…”

Section: Discussionmentioning

confidence: 99%

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Clostridioides difficileutilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

Hastie,

Carmichael,

Werner

et al. 2023

Preprint

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Clostridioides difficileremains a public health threat commonly observed following antibiotic use. Due to the importance of iron in many cell processes, most bacteria, includingC. difficile, have multiple mechanisms of acquiring iron. Previous studies have examined ferrous iron uptake inC. difficile, here we focus on the role of siderophores. In a growth assay, we show thatC. difficilecan use a variety of siderophores as the sole iron source. InC. difficile,two ABC transporters induced under low iron conditions are predicted siderophore importers: FhuDBGC and YclNOPQ. We hypothesized that these transporters are responsible for the uptake of the siderophores we tested. To investigate the specificity of these transporters, we purified the substrate binding proteins and examined siderophore binding using thermal shift. We demonstrate increased stability between one siderophore binding protein, FhuD, and the siderophore ferrichrome, suggesting a binding interaction. This specificity correlates with the inability of anΔfhuDBGCmutant to grow efficiently under iron limiting conditions in the presence of ferrichrome. WhileC. difficileused additional siderophores in our growth experiments, we did not observe increased thermal stability between the receptor proteins and any of the other siderophores tested, suggesting these siderophores do not bind these receptors and other siderophore import mechanisms remain to be elucidated. Redundancy in iron acquisition is a microbial survival adaptation to cope with the constant battle for iron within a host. Greater knowledge about howC. difficileacquires iron will provide insight about howC. difficilecolonizes and persists in the colon.IMPORTANCEThis study is the first example ofC. difficilegrowing with siderophores as the sole iron source and describes the characterization of the ferric hydroxamate uptake ABC transporter (FhuDBGC). This transporter shows specificity to the siderophore ferrichrome. While not required for pathogenesis, this transporter highlights the redundancy in iron acquisition mechanisms whichC. difficileuses to compete for iron during an infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clostridioides difficileutilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

Hastie,

Carmichael,

Werner

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Clostridioides difficile utilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

Hastie,

Carmichael,

Werner

et al. 2023

J Bacteriol

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Clostridioides difficile remains a public health threat commonly observed following antibiotic use. Due to the importance of iron in many cell processes, most bacteria, including C. difficile , have multiple mechanisms of acquiring iron. Previous studies have examined ferrous iron uptake in C. difficile ; here we focus on the role of siderophores. In a growth assay, we show that C. difficile can use a variety of siderophores as the sole iron source. In C. difficile, two ABC transporters induced under low iron conditions are predicted siderophore importers: FhuDBGC and YclNOPQ. We hypothesized that these transporters are responsible for the uptake of the siderophores we tested. To investigate the specificity of these transporters, we purified the substrate binding proteins and examined siderophore binding using thermal shift. We demonstrate increased stability between one siderophore binding protein, FhuD, and the siderophore ferrichrome, suggesting a binding interaction. This specificity correlates with the inability of an ΔfhuDBGC mutant to grow efficiently under iron limiting conditions in the presence of ferrichrome. While C. difficile used additional siderophores in our growth experiments, we did not observe increased thermal stability between the receptor proteins and any of the other siderophores tested, suggesting these siderophores do not bind these receptors and other siderophore import mechanisms remain to be elucidated. Redundancy in iron acquisition is a microbial survival adaptation to cope with the constant battle for iron within a host. Greater knowledge about how C. difficile acquires iron will provide insight about how C. difficile colonizes and persists in the colon. IMPORTANCE This study is the first example of C. difficile growing with siderophores as the sole iron source and describes the characterization of the ferric hydroxamate uptake ABC transporter (FhuDBGC). This transporter shows specificity to the siderophore ferrichrome. While not required for pathogenesis, this transporter highlights the redundancy in iron acquisition mechanisms that C. difficile uses to compete for iron during an infection.

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What’s metal got to do with it? Transition metals in Clostridioides difficile infection

Cited by 2 publications

References 60 publications

Clostridioides difficileutilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

Clostridioides difficileutilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

Clostridioides difficile utilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake

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