Utilization of Fe³⁺-acinetoferrin analogs as an iron source by Mycobacterium tuberculosis

• Published in: Biometals Vol. 21; no. 1; pp. 93 - 103
• Main Authors: Rodriguez, G. Marcela, Gardner, Richard, Kaur, Navneet, Phanstiel, Otto IV
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01-02-2008; Springer Netherlands; Springer Nature B.V
• Subjects: Acinetoferrin; Biochemistry; Biomedical and Life Sciences; Cell Biology; Citrates - chemistry; Citrates - metabolism; Exosiderophores; Ferric Compounds - chemistry; Ferric Compounds - metabolism; Gallium; Hydroxamic Acids - chemistry; Hydroxamic Acids - metabolism; Iron; Iron - chemistry; Iron - metabolism; Life Sciences; Medicine/Public Health; Microbiology; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - metabolism; Mycobactin; Pathogens; Pathology; Pharmacology/Toxicology; Plant Physiology; Proteins; siderophores; Siderophores - metabolism; Tuberculosis; Siderophores; Iron; Exosiderophores; Mycobacterium tuberculosis; Mycobactin; Acinetoferrin
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-007-9096-5

Mycobacterium tuberculosis, the causative agent of human tuberculosis, synthesizes and secretes siderophores in order to compete for iron (an essential micronutrient). Successful iron acquisition allows M. tuberculosis to survive and proliferate under the iron-deficient conditions encountered in the host. To examine structural determinants important for iron siderophore transport in this pathogen, the citrate-based siderophores petrobactin, acinetoferrin and various acinetoferrin homologs were synthesized and used as iron transport probes. Mutant strains of M. tuberculosis deficient in native siderophore synthesis or transport were utilized to better understand the mechanisms involved in iron delivery via the synthetic siderophores. Acinetoferrin and its derivatives, especially those containing a cyclic imide group, were able to deliver iron or gallium into M. tuberculosis which promoted or inhibited, respectively, the growth of this pathogen.