Post Savannah J, Shapiro Justin A, Wuest William M
Department of Chemistry , Emory University , Atlanta , GA 30322 , USA . Email:
Antibiotic Resistance Center , Emory University School of Medicine , Atlanta , GA 30322 , USA.
Medchemcomm. 2019 Mar 21;10(4):505-512. doi: 10.1039/c9md00032a. eCollection 2019 Apr 1.
The rise of antibiotic resistant bacteria has become a problem of global concern. Of particular interest are the ESKAPE pathogens, species with high rates of multi-drug resistant infections. Novel antibiotic mechanisms of action are necessary to compliment traditional therapeutics. Recent research has focused on targeting virulence factors as a method of combatting infection without creating selective pressure for resistance or damaging the host commensal microbiome. Some investigations into one such virulence behavior, iron acquisition, have displayed additional effects on another virulence behavior, biofilm formation. The use of exogenous iron-chelators, gallium as an iron mimic, and inhibition of siderophore-mediated iron acquisition are all strategies for disturbing iron-homeostasis that have implicated effects on biofilms. However, the exact nature of this connection remains ambiguous. Herein we summarize these findings and identify opportunities for further investigation.
抗生素耐药细菌的出现已成为一个全球关注的问题。特别值得关注的是ESKAPE病原体,即具有高多重耐药感染率的物种。新型抗生素作用机制对于补充传统治疗方法是必要的。最近的研究集中在靶向毒力因子,作为一种对抗感染的方法,而不会产生耐药性的选择压力或损害宿主共生微生物群。对一种这样的毒力行为,即铁获取的一些研究,显示出对另一种毒力行为,即生物膜形成的额外影响。使用外源性铁螯合剂、镓作为铁模拟物以及抑制铁载体介导的铁获取,都是扰乱铁稳态的策略,这些策略对生物膜有牵连效应。然而,这种联系的确切性质仍然不明确。在此,我们总结这些发现并确定进一步研究的机会。