Pramanik Avijit, Stroeher Uwe H, Krejci Juliane, Standish Alistair J, Bohn Erwin, Paton James C, Autenrieth Ingo B, Braun Volkmar
Microbiology/Membrane Physiology, University of Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
Int J Med Microbiol. 2007 Oct;297(6):459-69. doi: 10.1016/j.ijmm.2007.03.002. Epub 2007 Apr 24.
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.
白霉素属于铁载体霉素类，这类化合物由与抗生素部分相连的铁载体组成。已发现白霉素对具有功能性高铁羟肟酸盐转运系统的细菌具有活性，这意味着细菌会主动转运白霉素直至死亡。我们研究了白霉素对细菌病原体的活性谱，发现除变形杆菌属和摩根菌属外的肠杆菌科细菌均敏感。这两个属的耐药性是由于缺乏高铁羟肟酸盐转运系统。在革兰氏阳性菌中，金黄色葡萄球菌和肺炎链球菌高度敏感，而无乳链球菌、化脓性链球菌和表皮葡萄球菌则耐药。在感染肺炎链球菌或小肠结肠炎耶尔森菌的小鼠中检测了白霉素的体内疗效。单剂量10mg白霉素/千克体重可使小肠结肠炎耶尔森菌的菌落形成单位减少三到四个数量级。单剂量1mg白霉素/千克体重足以清除小鼠体内的肺炎链球菌感染。在与野生型肺炎链球菌及其白霉素耐药突变体的直接竞争实验中，突变体的回收率低于野生型，这表明该突变体在小鼠模型中的适应性降低。我们得出结论，在小鼠模型中，白霉素对清除革兰氏阳性菌和革兰氏阴性菌引起的感染有效。白霉素治疗可降低细菌载量，使免疫系统能够清除残留的白霉素耐药菌，因此白霉素类抗生素可作为治疗的辅助药物。铁载体转运系统充当特洛伊木马，将白霉素带入细菌。
