Department of Pharmacy Practice and Translational Research, University of Houston, Houston, TX 77204, USA.
Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, The 6th Affiliated Hospital of Shenzhen University Health Center, Shenzhen, Guangdong 518052, China.
Lett Appl Microbiol. 2023 Feb 16;76(2). doi: 10.1093/lambio/ovad019.
Acinetobacter baumannii (AB) has become multidrug-resistant (MDR) in recent years, and, currently, there are limited effective treatment options. Nutrient metals (e.g. iron) are essential to the metabolic functions of AB. This study examined the impact of iron chelation on the growth of AB in vitro and in vivo. Susceptible and MDR-AB bloodstream isolates (n = 9) were recovered from different patients between 2011 and 2018. Clonal diversity was ascertained by Fourier-transform infrared spectroscopy. In vitro bacterial densities were measured over 20 h to determine growth profiles. Variable amounts of a chelating agent [deferiprone (DFP)] were added to create a concentration gradient. Galleria mellonella larvae were inoculated with an isolate, with and without DFP. Quantitative culture was used to ascertain the bacterial burden of aggregate larvae immediately and 4 h post-infection. Increasing concentrations of DFP caused a transient and concentration-dependent hindrance to in vitro growth, compared to the no-treatment group. In vivo bacterial burden immediately post-infection in both groups was comparable. After 4 h, the burden was much higher in the control group comparatively (8.7 and 6.7 log CFU g-1). These results support that micro-nutrient limitation has the potential of being a novel approach for treating high-risk infections due to MDR-AB.
近年来,鲍曼不动杆菌(AB)已变得对多种药物耐药(MDR),目前有效的治疗选择有限。营养金属(例如铁)对 AB 的代谢功能至关重要。本研究探讨了铁螯合作用对 AB 体外和体内生长的影响。从 2011 年至 2018 年,从不同患者中回收了易感性和 MDR-AB 血流分离株(n=9)。傅里叶变换红外光谱法确定了克隆多样性。在 20 小时内测量细菌密度以确定生长曲线。添加不同量的螯合剂[去铁酮(DFP)]以形成浓度梯度。用分离株感染金蝇幼虫,有无 DFP。定量培养用于确定感染后立即和 4 小时时聚集幼虫的细菌负荷。与未处理组相比,DFP 浓度越高,体外生长的暂时性和浓度依赖性抑制作用越明显。两组感染后立即的体内细菌负荷相当。4 小时后,对照组的负荷明显更高(8.7 和 6.7 log CFU g-1)。这些结果表明,微量营养素限制有可能成为治疗由于 MDR-AB 引起的高危感染的新方法。