Phenazines and toxoflavin act as interspecies modulators of resilience to diverse antibiotics,Molecular Microbiology

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Phenazines and toxoflavin act as interspecies modulators of resilience to diverse antibiotics
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-05-05 , DOI: 10.1111/mmi.14915
Lucas A Meirelles ₁ , Dianne K Newman _{1,

2}

Affiliation

Bacterial opportunistic pathogens make diverse secondary metabolites both in the natural environment and when causing infections, yet how these molecules mediate microbial interactions and their consequences for antibiotic treatment are still poorly understood. Here, we explore the role of three redox-active secondary metabolites, pyocyanin, phenazine-1-carboxylic acid, and toxoflavin, as interspecies modulators of antibiotic resilience. We find that these molecules dramatically change susceptibility levels of diverse bacteria to clinical antibiotics. Pyocyanin and phenazine-1-carboxylic acid are made by Pseudomonas aeruginosa, while toxoflavin is made by Burkholderia gladioli, organisms that infect cystic fibrosis and other immunocompromised patients. All molecules alter the susceptibility profile of pathogenic species within the “Burkholderia cepacia complex” to different antibiotics, either antagonizing or potentiating their effects, depending on the drug’s class. Defense responses regulated by the redox-sensitive transcription factor SoxR potentiate the antagonistic effects these metabolites have against fluoroquinolones, and the presence of genes encoding SoxR and the efflux systems it regulates can be used to predict how these metabolites will affect antibiotic susceptibility of different bacteria. Finally, we demonstrate that inclusion of secondary metabolites in standard protocols used to assess antibiotic resistance can dramatically alter the results, motivating the development of new tests for more accurate clinical assessment.

中文翻译：

吩嗪和毒黄素作为种间调节剂对多种抗生素具有恢复力

细菌性机会病原体在自然环境中和引起感染时都会产生多种次级代谢产物，但这些分子如何介导微生物相互作用及其对抗生素治疗的影响仍知之甚少。在这里，我们探讨了三种具有氧化还原活性的次级代谢产物绿脓素、吩嗪-1-羧酸和毒黄素作为抗生素耐受性的种间调节剂的作用。我们发现这些分子显着改变了不同细菌对临床抗生素的敏感性水平。绿脓素和吩嗪-1-羧酸是由铜绿假单胞菌制造的，而毒黄素是由剑兰伯克氏菌制造的，感染囊性纤维化和其他免疫功能低下患者的生物体。所有分子都会改变“洋葱伯克霍尔德菌”中致病菌种的易感性复杂”到不同的抗生素，拮抗或加强它们的作用，这取决于药物的类别。由氧化还原敏感转录因子 SoxR 调节的防御反应增强了这些代谢物对氟喹诺酮类药物的拮抗作用，编码 SoxR 的基因及其调节的外排系统的存在可用于预测这些代谢物将如何影响不同细菌的抗生素敏感性。最后，我们证明在用于评估抗生素耐药性的标准方案中包含次级代谢物可以显着改变结果，从而推动开发新测试以进行更准确的临床评估。

更新日期：2022-05-05

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