LAUSR

The vertebrate lung is the organ with the largest surface area presented to the external environment. The combined alveolar surface area of both adult human lungs is about 100 m [1], and typically 10,000 to 20,000 liters of air are inhaled per day [2]. Coupled with the fact that fungal spore densities of 10 to 50 spores per liter of air are common [3, 4], the average person inhales up to 100,000 or more fungal spores daily. Lung surface areas and inhalation volumes for small mammals are comparable to those of humans when scaled for size. Moreover, many small mammals live in microenvironments (notably burrows and understories) where they are exposed to high densities of airborne spores derived from the growth of fungi on substrates in soil and litter. While lung tissues have physical and immunological defenses against infection, it is also the case that the air and blood-vessel interface is by necessity fragile. Taken together, these factors make it unsurprising that many fungi have adaptations that permit commensal, pathogenic, and perhaps, yet to be discovered, mutualistic relationships with lungs. The title of this article references the fact that the study of interactions between lungs and certain fungi began in the first half of the 20th century. As we discuss here, modern molecular methods combined with culture-based approaches are revealing that lung mycobiomics is a field rich in opportunities for studying interactions of fungi across the vertebrate tree of life. Moreover, next-generation sequencing efforts now provide important new contexts for the study of lung-inhabiting fungi that began more than seven decades ago. Here, we briefly cover the historical context of the lung mycobiome, discuss future directions and questions, and propose that the lung mycobiome may form a reservoir for opportunistic fungal mycoses caused by commensal lung-adapted fungi. We discuss the following points: (1) Human lungs have a mycobiome. (2) Lungs of nonhuman mammals commonly possess a diversity of fungi. (3) Studies of fungi associated with lungs have implications for the ecology, distribution, and pathogenicity of specific fungi, especially members of the Onygenales and species of Pneumocystis. (4) A framework is needed to distinguish among lung-adapted fungi (some of which can be opportunistic pathogens), members of the general mammalian mycobiome, and fungi that are present in lungs because of incidental inhalation. (5) Museum research collections provide an important resource for addressing these issues. PLOS PATHOGENS