Tejeda-Garibay Susana, Zhao Lihong, Hum Nicholas R, Pimentel Maria, Diep Anh L, Amiri Beheshta, Sindi Suzanne S, Weilhammer Dina R, Loots Gabriela G, Hoyer Katrina K
Quantitative and Systems Biology, Graduate Program, University of California Merced, CA.
Biosciences and Biotechnology Division, Lawrence Livermore National Laboratories, Livermore CA.
bioRxiv. 2023 Oct 23:2023.10.23.563655. doi: 10.1101/2023.10.23.563655.
Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen . Unfortunately, patients are often misdiagnosed with bacterial pneumonia leading to inappropriate antibiotic treatment. Soil bacteria -like species exhibits antagonistic properties against ; however, the antagonistic capabilities of host microbiota against are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of . We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of while partial depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2xGYE (GYE) and CNA w/ 5% sheep's blood agar (5%SB-CNA) inhibited the growth of , but that grown on chocolate agar does not. Partial depletion of the microbiota through antibiotic disk diffusion revealed that microbiota depletion leads to diminished inhibition and comparable growth of growth to controls. To characterize the bacteria grown and narrow down potential candidates contributing to the inhibition of , 16s rRNA sequencing of tracheal and intestinal agar cultures and murine lung extracts was performed. The identity of host bacteria that may be responsible for this inhibition was revealed. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth .
球孢子菌病,也称为谷热,是一种由真菌病原体引起的疾病。不幸的是,患者常常被误诊为细菌性肺炎,从而导致不恰当的抗生素治疗。土壤中类似细菌的物种对该真菌病原体具有拮抗特性;然而,宿主微生物群对该真菌病原体的拮抗能力尚未得到探索。我们试图研究气管和肠道微生物群抑制该真菌病原体生长的潜力。我们假设,从无抗生素小鼠获得的连续微生物菌苔会抑制该真菌病原体的生长,而通过抗生素纸片扩散法部分清除微生物群将为真菌生长留出空间。我们观察到,在2xGYE(葡萄糖酵母提取物培养基)和含5%羊血琼脂的哥伦比亚琼脂培养基(5%SB-CNA)上生长的微生物群抑制了该真菌病原体的生长,但在巧克力琼脂上生长的微生物群则没有。通过抗生素纸片扩散法部分清除微生物群后发现,微生物群的清除导致抑制作用减弱,该真菌病原体的生长与对照组相当。为了鉴定生长的细菌并缩小可能导致抑制该真菌病原体生长的潜在候选菌范围,我们对气管和肠道琼脂培养物以及小鼠肺提取物进行了16s rRNA测序。揭示了可能负责这种抑制作用的宿主细菌的身份。这项研究的结果证明了宿主微生物群抑制该真菌病原体生长的潜力,并表明通过抗生素治疗改变微生物群可能会对有效的真菌清除产生负面影响,并为真菌生长留出空间。