High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections.
High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections.
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源自囊性纤维化肺部感染的铜绿假单胞菌群体中脂多糖突变体和 R2-Pyocin 敏感变异体的患病率很高。
DOI：
10.1101/2023.04.26.538445
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Diggle,StephenP
中科院分区：
文献类型：
--
作者：
Mei,Madeline;Pheng,Preston;Kurzeja-Edwards,Detriana;Diggle,StephenP
囊性纤维化（CF）肺部的慢性、高度耐药感染导致发病率和死亡率增加。铜绿假单胞菌是一种常见的CF病原体，对多种抗生素表现出耐药性，导致抗菌药物耐药性（AMR）。这些细菌群体显示出遗传和表型多样性，但目前还不清楚这种多样性如何影响对细菌素的敏感性。R-绿脓菌素，即，产细菌素。铜绿假单胞菌是噬菌体尾样抗微生物剂。R-绿脓菌素具有潜在的抗菌活性，然而，最近的研究表明，P. CF肺部感染内的嗜氧菌变异体导致对R-绿脓菌素的不同易感性。这种变化可能与充当R-绿脓菌素受体的脂多糖（LPS）的变化有关。目前，尚不清楚R-绿脓菌素敏感菌株在慢性CF肺部感染中的频率，特别是考虑到这些菌株内的异质性时。在这项研究中，我们测试了R2-绿脓菌素的敏感性139铜绿假单胞菌变种从7 CF患者的17个痰液样本，并分析了LPS表型。我们发现，83%的痰液样本没有R2-绿脓菌素耐药变体，而几乎所有样本都含有敏感变体。LPS表型和R2-绿脓菌素敏感性之间没有相关性，但我们估计约76%的大肠杆菌衍生的变体缺乏O-特异性抗原，40%缺乏共同抗原，24%改变了LPS核心。LPS表型和R-绿脓菌素敏感性之间不存在相关性表明LPS堆积密度可能在CF变体中的R-绿脓菌素敏感性中起重要作用。我们的研究支持R-绿脓菌素作为治疗剂的潜力，因为许多感染性CF变体对R2-绿脓菌素敏感，即使在不同的细菌种群中也是如此。重要的是，囊性纤维化（CF）患者经常经历由耐药铜绿假单胞菌引起的慢性、使人衰弱的肺部感染，从而导致抗菌素耐药性（AMR）。研究表明，中国对虾的遗传多样性和表型多样性均高于日本对虾。CF肺中的需氧菌群引起了关于其对非传统抗菌剂（如细菌素）的易感性的问题。在这项研究中，我们专注于R-绿脓菌素，一种具有高效力和窄杀伤谱的细菌素。我们的研究结果表明，大量的感染性CF变体对R2-绿脓菌素敏感，即使在不同的细菌群体中，也支持它们作为治疗剂的潜在用途。脂多糖（LPS）表型和R-绿脓菌素敏感性之间没有明确的相关性表明，LPS堆积密度可能在CF变体中的R-绿脓菌素敏感性中起重要作用。了解LPS表型和R-绿脓菌素敏感性之间的关系对于开发这些慢性感染的有效治疗至关重要。
Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality.Pseudomonas aeruginosa, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e., bacteriocins produced byP. aeruginosa, are phage-tail-like antimicrobials. R-pyocins have potential as antimicrobials, however, recent research suggests the diversity ofP. aeruginosavariants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested the R2-pyocin susceptibility of 139P.aeruginosavariants from 17 sputum samples of 7 CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. There was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations.IMPORTANCECystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistantPseudomonas aeruginosa, contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity ofP. aeruginosapopulations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum. Our findings indicate that a large number of infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations, supporting their potential use as therapeutic agents. The absence of a clear correlation between lipopolysaccharide (LPS) phenotypes and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Understanding the relationship between LPS phenotypes and R-pyocin susceptibility is crucial for developing effective treatments for these chronic infections.
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