Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica and Streptococcus pneumoniae.
Albomycin belongs to the class of sideromycins, compounds composed of iron carriers linked to antibiotic moieties. Albomycin was found to be active against bacteria that have a functional ferric hydroxamate transport system meaning that bacteria will actively transport albomycin until they die. We examined the activity spectrum of albomycin for bacterial pathogens and found that Enterobacteriaceae except species of Proteus and Morganella were sensitive. Resistance in the two genera was due to the lack of the ferric hydroxamate transport system. Among Gram-positive bacteria, Staphylococcus aureus and Streptococcus pneumoniae were highly sensitive, whereas Streptococcus agalactiae, Streptococcus pyogenes, and Staphylococcus epidermidis were resistant. The in vivo efficacy of albomycin was examined in mice infected with S. pneumoniae or Yersinia enterocolitica. A single dose of 10mg albomycin/kg body weight reduced the colony-forming units of Y. enterocolitica by three to four orders of magnitude. A single dose of 1mg albomycin/kg body weight was sufficient to clear S. pneumoniae infections in mice. In direct competition experiments with wild-type S. pneumoniae and its albomycin-resistant mutant, the recovery rate of the mutant was lower than for the wild-type indicating that the mutant had reduced fitness in the mouse model. We conclude that albomycin is effective in clearing infections caused by both Gram-positive and Gram-negative bacteria in a mouse model. Albomycin treatment reduces the bacterial load allowing the immune system to remove residual albomycin-resistant bacteria, and as such would make albomycin-based antibiotics an adjunct to treatment. The ferrichrome transport system serves as a Trojan horse to get albomycin into bacteria.
Pramanik
Avijit
A
Microbiology/Membrane Physiology, University of Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
Stroeher
Uwe H
UH
Krejci
Juliane
J
Standish
Alistair J
AJ
Bohn
Erwin
E
Paton
James C
JC
Autenrieth
Ingo B
IB
Braun
Volkmar
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005291:Ferrichrome / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology; D015009:Yersinia Infections / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D005291:Ferrichrome; C015657:albomycin