Sass Gabriele, Kethineni Satya, Stevens David A
California Institute for Medical Research, San Jose, CA 95128, USA.
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pathogens. 2024 Oct 7;13(10):875. doi: 10.3390/pathogens13100875.
(Af) and (Pa) are pathogens inhabiting the lungs of persons with cystic fibrosis (CF), or immune-compromised patients, causing or aggravating disease. We previously investigated their microbial interaction as well as susceptibility to anti-fungal drugs using RPMI medium (contains undetectable iron concentrations), as is standard for susceptibility testing. Here we investigated microbial interaction in synthetic sputum medium (SSPM), a complex mixture designed to mimic the milieu in CF lungs. SSPM contains Fe. Pa laboratory strain PA14 or PA14 siderophore mutant planktonic culture filtrate, prepared in RPMI or SSPM, were compared for inhibition of Af biofilm formation. SSPM enhanced bacterial and fungal growth and the production of the Pa molecules pyoverdine, phenazines, and rhamnolipids. Af was more susceptible to these molecules in SSPM (with the exception of pyoverdine). SSPM interfered with fungal susceptibility to pyoverdine. Studies with the mutant helped to reveal that the reduced anti-fungal activity of pyoverdine in SSPM appears to be compensated by higher production of other anti-fungal molecules, e.g., rhamnolipids, phenazines, and PQS, and higher Af sensitivity to these molecules. In summary, SSPM better defines Pa-Af intermicrobial competition in the milieu of CF lungs.
烟曲霉（Af）和铜绿假单胞菌（Pa）是寄居于囊性纤维化（CF）患者或免疫功能低下患者肺部的病原体，可引发疾病或使病情加重。我们之前使用RPMI培养基（铁浓度检测不到，这是药敏试验的标准培养基）研究了它们之间的微生物相互作用以及对抗真菌药物的敏感性。在此，我们在合成痰液培养基（SSPM）中研究了微生物相互作用，SSPM是一种旨在模拟CF肺部环境的复杂混合物，含有铁元素。比较了在RPMI或SSPM中制备的Pa实验室菌株PA14或PA14铁载体突变体的浮游培养滤液对Af生物膜形成的抑制作用。SSPM促进了细菌和真菌的生长以及Pa分子绿脓菌素、吩嗪和鼠李糖脂的产生。在SSPM中，Af对这些分子（绿脓菌素除外）更敏感。SSPM干扰了真菌对绿脓菌素的敏感性。对突变体的研究有助于揭示，SSPM中绿脓菌素抗真菌活性的降低似乎被其他抗真菌分子（如鼠李糖脂、吩嗪和2-庚基-3-羟基-4（1H）-喹诺酮（PQS））的更高产量以及Af对这些分子的更高敏感性所补偿。总之，SSPM能更好地界定CF肺部环境中Pa-Af之间的微生物竞争。
