Acinetobactin Isomerization Enables Adaptive Iron Acquisition in Acinetobacter baumannii through pH-Triggered Siderophore Swapping.
Pathogenic strains of Acinetobacter baumannii excrete multiple siderophores that enhance iron scavenging from host sources. The oxazoline siderophore pre-acinetobactin undergoes an unusual non-enzymatic isomerization, producing the isoxazolidinone acinetobactin. In this study, we explored the kinetics, mechanism, and biological consequence of this siderophore swapping. Pre-acinetobactin is excreted to the extracellular space where the isomerization to acinetobactin occurs with a pH-rate profile consistent with 5-exo-tet cyclization at C5' with clean stereochemical inversion. Pre-acinetobactin persists at pH <6, and acinetobactin is rapidly formed at pH >7, matching each siderophore's pH preference for iron(III) chelation and A. baumannii growth promotion. Acinetobactin isomerization provides two siderophores for the price of one, enabling A. baumannii to sequester iron over a broad pH range likely to be encountered during the course of an infection.
Department of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
Justin A
JA
Shapiro
Department of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
Timothy A
TA
Wencewicz
D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007536:Isomerism; D005810:Multigene Family; D010080:Oxazoles / Q000737:chemistry* / Q000378:metabolism; D017262:Siderophores / Q000378:metabolism*
D007093:Imidazoles; D010080:Oxazoles; D017262:Siderophores; C091186:acinetobactin; D007501:Iron
Acinetobacter baumannii; acinetobactin; antibiotic resistance; antivirulence; siderophore