The hiuABC Operon Mediates Xenosiderophore Utilization in Caulobacter crescentus

Area of Science:

• Microbiology
• Bacterial Physiology
• Iron Metabolism

Background:

• Caulobacter species inhabit iron-limited environments, necessitating efficient iron acquisition strategies.
• Diderm bacteria like Caulobacter crescentus utilize outer-membrane TonB-dependent transporters (TBDTs) for ferric siderophore complex uptake.
• C. crescentus lacks known siderophore synthesis but possesses multiple TBDTs regulated by ferric uptake repressor (Fur), suggesting xenosiderophore scavenging.

Purpose of the Study:

• To identify genes in C. crescentus essential for utilizing external siderophores (xenosiderophores) for iron acquisition.
• To characterize the function of the identified HiuABC system in iron uptake from hydroxamate-family siderophores.

Main Methods:

• A barcoded transposon screen was employed using ferrioxamine B (FXB) as a model hydroxamate siderophore.
• Genetic analysis was performed to determine the roles of HiuA, HiuB, and HiuC in iron acquisition.
• Substrate specificity was assessed for ferrioxamines and ferrichrome (FC).

Main Results:

• The conserved, Fur-regulated hiuABC operon was identified as crucial for ferrioxamine B (FXB) iron acquisition.
• HiuA functions as the primary TBDT for ferrioxamines and ferrichrome (FC).
• HiuB and HiuC form a complex required for FXB and ferrioxamine E (FXE) utilization, while HiuC is dispensable for FC uptake, indicating substrate-specific roles.

Conclusions:

• The hiuABC operon enables C. crescentus to acquire iron from structurally diverse hydroxamate-family siderophores.
• This system is vital for bacterial survival and iron homeostasis in iron-scarce ecosystems.
• The findings reveal a conserved mechanism for xenosiderophore utilization in bacteria.