The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol.
The Iron Content of Human Serum Albumin Modulates the Susceptibility of Acinetobacter baumannii to Cefiderocol.
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DOI：
10.3390/biomedicines11020639
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发表时间：
2023-02-20
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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感染鲍曼不动杆菌的患者接受头孢地罗可（CFDC）治疗的死亡率不如接受肺部和血液感染最佳治疗的患者。先前的研究表明，生长培养基中人血清白蛋白（HSA）或含HSA的液体（如人血清（HS）或人胸膜液（HPF））的存在与高亲和力铁载体介导的铁摄取系统相关基因表达的降低相关。这些观察结果可以解释CFDC在肺部和血流感染中观察到的临床表现的复杂性，因为铁铁载体转运蛋白增强CFDC渗透到细菌细胞中。从HS或HPF中去除HSA导致CFDC的最小抑菌浓度（MIC）降低。伴随着这些结果，增强的TonB依赖性转运蛋白的表达，已知在运输铁中发挥关键作用进行了观察。除了诱导铁摄取基因表达的改变外，去除HSA还降低了β-内酰胺酶基因的表达。总而言之，这些观察结果表明环境HSA对选择A的表达水平具有作用。鲍曼不动杆菌基因此外，从HSA中去除铁与去除HSA对与铁摄取系统相关的基因的表达具有相同的效果，这也表明HSA调节某些基因表达的机制中的至少一种是通过充当铁源。
The mortality rates of patients infected with Acinetobacter baumannii who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with high-affinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell. The removal of HSA from HS or HPF resulted in a reduction in the minimal inhibitory concentration (MIC) of CFDC. Concomitant with these results, an enhancement in the expression of TonB-dependent transporters known to play a crucial role in transporting iron was observed. In addition to inducing modifications in iron-uptake gene expression, the removal of HSA also decreased the expression of β-lactamases genes. Taken together, these observations suggest that environmental HSA has a role in the expression levels of select A. baumannii genes. Furthermore, the removal of iron from HSA had the same effect as the removal of HSA upon the expression of genes associated with iron uptake systems, also suggesting that at least one of the mechanisms by which HSA regulates the expression of certain genes is through acting as an iron source.
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