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Background:  Infections caused by  Candida  species and  Staphylococcus aureus  are associated with biofilm formation.  C. albicans–S. aureus  interactions are synergistic due to the significant increase in mixed biofilms and improved resistance to vancomycin of  S. aureus .  C. glabrata  and  S. aureus  both are nosocomial pathogens that cause opportunistic infections in similar host niches. However, there is scarce information concerning the interaction between these last microorganisms.   Results:  The relationship between  C. glabrata  and  S. aureus  was evaluated by estimating the viability of both microorganisms in co-culture of planktonic cells and in single and mixed biofilms. An antagonistic behavior of  S. aureus  and their cell-free bacterial supernatant (CFBS) toward  C. glabrata , both in planktonic form and in biofilms, was demonstrated. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM) images showed yeast cells surrounded by bacteria, alterations in intracytoplasmic membranes, and non-viable blastoconidia with intact cell walls. Concomitantly,  S. aureus  cells remained viable and unaltered. The antagonistic activity of  S. aureus  toward  C. glabrata  was not due to cell-to-cell contact but the presence of CFBS, which causes a significant decrement in yeast viability and the formation of numerous lipid droplets (LDs), reactive oxygen species (ROS) accumulation, as well as nuclear alterations, and DNA fragmentation indicating the induction of an apoptotic mechanism.   Conclusion:  Our results demonstrate that the  S. aureus  CFBS causes cell death in  C. glabrata  by an apoptotic mechanism.

Antagonistic Interaction of Staphylococcus aureus Toward Candida glabrata During in vitro Biofilm Formation Is Caused by an Apoptotic Mechanism