Evaluating the in vitro inhibition potential of host microbiota and plant extracts against Valley fever
Abstract
Coccidioidomycosis, also known as Valley fever, is primarily a respiratory disease caused by the fungal pathogen Coccidioides. The fungus predominantly inhabits the soil of the Southwestern United States, but the area of endemicity is expected to expand with global warming. Inhalation of the fungal spores leads 40% of patients to experience flu-like symptoms. Similarities in symptomology and fibrosis in chest x-ray often lead to misdiagnosis of Valley fever as bacterial pneumonia. Patients undergo several rounds of antibiotic treatment prior to accurate diagnosis, resulting in a perturbed microbiome and contributing to antibiotic resistance. The effect that a perturbed microbiota has on Coccidioides is unexplored; however, a soil B. subtilis-like species inhibits the growth of Coccidioides. We show that, in vitro, the intestinal and tracheal microbiomes can inhibit Coccidioides growth on select agar. Results also indicate that perturbing an established microbiome with an antibiotic disk cocktail eliminates the inhibitory effects of the microbiome and creates a niche for Coccidioides growth. Sequencing data revealed that the predominant genus responsible for the inhibition may belong to the Lactobacillus and Staphylococcus genus; with the addition of Bifidobacterium and Achromobacter found in the whole lung extracts. These bacteria with inhibitory potential could serve therapeutic purposes for this infection. Currently, fluconazole and amphotericin B are the primary antifungals used to treat coccidioidomycosis; however, these treatments have adverse side effects. Although most patients recover, 1% can develop disseminated disease leading to lifelong treatment as these antifungals are suppressive, not lethal to the fungus. In addition to these potential probiotic therapies, through our compound screens, we have found that avocado tree extracts could also have antifungal properties against Coccidioides. Together, probiotics and avocado compound extracts could potentially serve as supplemental therapies to the current antifungal drugs.