Utilization of Fe3+-acinetoferrin analogs as an iron source by Mycobacterium tuberculosis.
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.
Rodriguez
G Marcela
GM
The Public Health Research Institute at the International Center for Public Health, University of Medicine and Dentistry of New Jersey, 225 Warren Street, Newark, NJ 07103-3535, USA. marcela@phri.org
Gardner
Richard
R
Kaur
Navneet
N
Phanstiel
Otto
O
D002951:Citrates / Q000737:chemistry / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism
D002951:Citrates; D005290:Ferric Compounds; D006877:Hydroxamic Acids; D017262:Siderophores; C086668:acinetoferrin; D007501:Iron