Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates of Achromobacter Species and Correlate with Modifications of the Lipid A Moiety of Lipopolysaccharide.
Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates of Achromobacter Species and Correlate with Modifications of the Lipid A Moiety of Lipopolysaccharide.
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DOI：
10.1128/spectrum.03729-22
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发表时间：
2023-02-14
影响因子：
3.7
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中科院分区：
文献类型：
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Achromobacter属包括可导致免疫受损患者慢性感染的机会性病原体，特别是囊性纤维化(CF)患者。无色杆菌感染的治疗因抗菌素耐药性而变得复杂。在这项研究中，收集了来自CF源和非CF源的Achromobacter临床分离株，对多粘菌素B(PMB)的耐药性进行了调查。此外，还检测了PMB挑战对部分分离株的影响，并描述了分离株中存在耐PMB的亚群。此外，对Achromobacter临床分离株的脂类A的化学和质谱分析能够确定最常见的结构，并表明PMB的挑战与脂类A的修饰有关，包括添加氨基葡萄糖和棕榈酰化，以及伴随而来的C-1位游离磷酸盐的损失。这项研究表明，与PMB耐药性相关的脂质A修饰在Achromobacter中普遍存在，并且可以从PMB敏感的Achromobacter临床分离株中选择和分离出具有正电荷残基和附加的酰基链的亚耐药群体。重要性无色杆菌可导致免疫功能低下患者的慢性和潜在严重感染，特别是囊性纤维化患者。由于Achromobacter固有的多重耐药性，细菌无法被根除。我们报告了对多粘菌素B(PMB)的内在耐药性，多粘菌素B是一种用于治疗多重耐药细菌感染的最后抗菌肽，在Achromobacter临床分离株中普遍存在；许多菌株在PMB挑战时也表现出更高的耐药性。对几种脱色杆菌的脂多糖脂A的分析表明，在耐PMB的菌株中有一种五酰化的类脂A，在耐PMB的菌株中，它被氨基葡萄糖残基、一个额外的酰链、磷酸盐的损失和酰链的羟基化所修饰，所有这些都可以增强其他细菌对PMB的抗性。我们得出结论，对PMB的耐药性，特别是在慢性呼吸道感染的Achromobacter分离株中，是一种常见的现象，并且Achromobacter lide A显示了可能增加对多粘菌素和潜在的其他抗菌肽的耐药性的修饰。
The Achromobacter genus includes opportunistic pathogens that can cause chronic infections in immunocompromised patients, especially in people with cystic fibrosis (CF). Treatment of Achromobacter infections is complicated by antimicrobial resistance. In this study, a collection of Achromobacter clinical isolates, from CF and non-CF sources, was investigated for polymyxin B (PmB) resistance. Additionally, the effect of PmB challenge in a subset of isolates was examined and the presence of PmB-resistant subpopulations within the isolates was described. Further, chemical and mass spectrometry analyses of the lipid A of Achromobacter clinical isolates enabled the determination of the most common structures and showed that PmB challenge was associated with lipid A modifications that included the addition of glucosamine and palmitoylation and the concomitant loss of the free phosphate at the C-1 position. This study demonstrates that lipid A modifications associated with PmB resistance are prevalent in Achromobacter and that subresistant populations displaying the addition of positively charged residues and additional acyl chains to lipid A can be selected for and isolated from PmB-sensitive Achromobacter clinical isolates. IMPORTANCE Achromobacter species can cause chronic and potentially severe infections in immunocompromised patients, especially in those with cystic fibrosis. Bacteria cannot be eradicated due to Achromobacter's intrinsic multidrug resistance. We report that intrinsic resistance to polymyxin B (PmB), a last-resort antimicrobial peptide used to treat infections by multiresistant bacteria, is prevalent in Achromobacter clinical isolates; many isolates also display increased resistance upon PmB challenge. Analysis of the lipopolysaccharide lipid A moiety of several Achromobacter species reveals a penta-acylated lipid A, which in the PmB-resistant isolates was modified by the incorporation of glucosamine residues, an additional acyl chain, loss of phosphates, and hydroxylation of acyl chains, all of which can enhance PmB resistance in other bacteria. We conclude that PmB resistance, particularly in Achromobacter isolates from chronic respiratory infections, is a common phenomenon, and that Achromobacter lipid A displays modifications that may confer increased resistance to polymyxins and potentially other antimicrobial peptides.