Biocontrol of Aspergillus niger in 3D-lung cell tissues by oxalotrophic bacteria

Aspergillus fungi are opportunistic pathogens that affect a large number of people worldwide. Many aspects of Aspergillus spp. pathogenesis toward humans are known, but their ability to enhance their infectious potential by manipulating the environmental pH of its host has not been considered yet. In this study, we tested the hypothesis that by producing oxalic acid, Aspergillus niger can manipulate pH during lung infection and thus, interfering with this process could limit pathogenicity. To test this hypothesis, we co-cultured A. niger with oxalotrophic bacteria in increasingly complex testing systems (Petri dishes and 3D-cell cultures systems). In in vitro tests, oxalotrophic bacteria limit oxalic acid production and suppressed the pH shift induced by A. niger. In 3D-cell cultures (Transwells(R) and Bronchioles-on-a-chip), A. niger also modified pH, Ca2+ and oxalic acid concentrations. Co-inoculation with as little as 10 cells of the oxalatrophic bacterium strongly inhibited the germination and development of A. niger and returned each of the three parameters to the baseline physiological values of uninfected cells. This biocontrol interaction between oxalotrophic bacteria and oxalate-producing A. niger could represent a paradigm shift in the fight against opportunistic fungal pathogens, where the host environment is rendered less permissive to fungal development.