Abstract
The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream; however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and systemic infection (peritonitis) murine models. According to the transcriptome analysis of the dual-species culture, virulence factors of S. aureus were significantly upregulated. Surprisingly, the beta-lactams and vancomycin-resistant genes in S. aureus as well as azole-resistant genes in C. albicans were also significantly increased. The synergistic effects on drug resistance to both antibacterial and antifungal agents were further proved both in vitro and in cutaneous abscess and peritonitis murine models treated by methicillin, vancomycin and fluconazole. The synergistic interactions between S. aureus and C. albicans on pathogenesis and drug resistance highlight the importance of targeting the microbial interactions in polyspecies-associated infections.
Highlights
The interactions between microbial species can impact pathogenic behaviors such as proliferation, virulence, and antibiotic tolerance during polyspecies-related infections [1,2,3,4]
C. albicans can increase the resistance of S. aureus to vancomycin about 100-fold [24], while C. albicans and S. aureus dual-species infection was shown to be concomitantly desensitized to miconazole treatment in a Galleria mellonella model [29]
A green fluorescent protein (GFP) expressing S. aureus strain was employed for assessing the effect of C. albicans on the proliferation of S. aureus
Summary
The interactions between microbial species can impact pathogenic behaviors such as proliferation, virulence, and antibiotic tolerance during polyspecies-related infections [1,2,3,4]. The increase of virulence of polyspecies-related infections caused by interspecies interactions can lead to poor prognosis of patients [8,9]. In a Galleria mellonella larvae testing model, co-infection by S. aureus and C. albicans significantly reduced the larval survival rate, with a higher density of S. aureus [28]. C. albicans can increase the resistance of S. aureus to vancomycin about 100-fold [24], while C. albicans and S. aureus dual-species infection was shown to be concomitantly desensitized to miconazole treatment in a Galleria mellonella model [29]
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