Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.
Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.
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宿主气管和肠道微生物组在体外抑制球孢子菌生长。
DOI：
10.1101/2023.10.23.563655
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hoyer,KatrinaK
中科院分区：
文献类型：
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作者：
Tejeda-Garibay,Susana;Zhao,Lihong;Hum,NicholasR;Pimentel,Maria;Diep,AnhL;Amiri,Beheshta;Sindi,SuzanneS;Weilhammer,DinaR;Loots,GabrielaG;Hoyer,KatrinaK
球孢子菌病，也被称为山谷热，是一种由真菌病原球孢子菌引起的疾病。不幸的是，患者经常被误诊为细菌性肺炎，导致不适当的抗生素治疗。土壤中的枯草芽孢杆菌样菌在体外对球孢子菌具有拮抗作用，但宿主菌群对球孢子菌的拮抗能力尚未得到研究。我们试图研究气管和肠道微生物组在体外抑制球孢子菌生长的潜力。我们假设，从无菌小鼠中获得的不间断菌苔会抑制球孢子菌的生长，而通过抗生素纸片扩散试验进行的部分体外耗竭将为真菌生长提供一个利基。我们观察到生长在2×GYE（GYE）和哥伦比亚粘杆菌素和萘啶酸与5%羊血琼脂上的微生物群抑制球孢子菌的生长，而生长在巧克力琼脂上的微生物群则不抑制。通过抗生素盘扩散部分消耗微生物群，显示抑制作用减弱，并且球孢子菌的生长与对照相当。为了表征生长的细菌并鉴定有助于抑制球孢子菌的潜在候选物，对气管和肠琼脂培养物以及小鼠肺提取物进行了16 S rRNA测序。我们发现，可能负责这种抑制的宿主细菌主要包括乳酸杆菌和葡萄球菌。这项研究的结果表明，宿主菌群有可能抑制球孢子菌在体外的生长，并表明通过抗生素治疗改变的微生物组可能会对有效的真菌清除产生负面影响，并为真菌在体内的生长提供一个小生境。重要的是，球孢子菌病是由真菌病原体侵入宿主肺部引起的，导致呼吸窘迫。2019年，CDC报告了20，003例谷热病例。然而，这一数字可能大大低估了山谷热病例的真实数量，因为许多病例由于检测策略不佳和缺乏诊断模型而未被发现。山谷热也经常被误诊为细菌性肺炎，导致60%-80%的患者在准确诊断之前接受抗生素治疗。误诊导致抗生素耐药性和抗生素诱导的微生物群失调问题日益严重;对疾病结局的影响目前尚不清楚。大约5%-10%有症状的山谷热患者发展为慢性肺病。山谷热会造成严重的经济负担和生活质量下降。关于什么因素导致慢性感染的发展知之甚少，并且对该疾病的治疗有限。
Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogenCoccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soilBacillus subtilis-like species exhibits antagonistic properties againstCoccidioides in vitro; however, the antagonistic capabilities of host microbiota againstCoccidioidesare unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth ofCoccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth ofCoccidioides,while partialin vitrodepletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheep’s blood agar inhibited the growth ofCoccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth ofCoccidioidesto controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition ofCoccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily includedLactobacillusandStaphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth ofCoccidioides in vitroand suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growthin vivo.IMPORTANCECoccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%–80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%–10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.