Antagonistic Interaction of Staphylococcus aureus and Staphylococcus epidermidis with Rhizopus arrhizus Mediated by Phenol Soluble Modulins and Organic Acids.

Rhizopus arrhizus ( R. arrhizus ) is a common causative agent of mucormycosis that usually enters the human body through the respiratory tract and skin. Both these sites harbor staphylococci as a part of the normal microflora, indicating the possibility of interspecies interactions. We aimed to elucidate this interaction and identify the molecular mechanisms involved. Both Staphylococcus aureus ( S. aureus ) and Staphylococcus epidermidis ( S. epidermidis ) substantially hindered R. arrhizus radial growth, spore germination, and liquid culture biomass. Secreted components in the stationary-phase supernatant were responsible for this activity. The active components, based on molecular weight-based fractionation, mass spectrometry, and ion exclusion chromatography, were identified as a truncated version of phenol soluble modulin α2 (Δ1Δ2PSMα2) and PSMα3 in S. aureus , PSMδ in S. epidermidis , and organic acids in both the species. Exposure to the phenol soluble modulins (PSMs) extensively damaged the fungal spores and pre-existing hyphae, leading to bleb formation, shriveling, hyphal shrinkage, and cell distortion.