Staphylococcus aureus Synergized with Candida albicans to Increase the Pathogenesis and Drug Resistance in Cutaneous Abscess and Peritonitis Murine Models

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.

Enhanced Virulence of Candida albicans by Staphylococcus aureus: Evidence in Clinical Bloodstream Infections and Infected Zebrafish Embryos

“…Our embryo infection result suggested C. albicans cobiofilm protects S. aureus against antimicrobials, and the major toxin genes of S. aureus are significantly upregulated, including hla and hlgB, resulting in high mortality for C. albicans SC5314-infected embryos. An upregulation of virulence factors in S. aureus, including hla, hlgB, enterotoxin family protein, staphylocoagulase, staphylococcal protein A, nucleases, intercellular adhesion proteins, fibronectin-binding proteins, drug-resistant genes glmU, murC, and murD, and penicillin-binding proteins, was demonstrated by Hu et al using cutaneous abscess and peritonitis murine models [25]. The increase in toxin production, especially exterotoxins, damages tissues and induces severe inflammation, which can cause multi-organ failure.…”

“…S. aureus toxin genes were augmented by C. albicans in murine infection models, including hla (alpha hemolysin) and hlgB (gamma hemolysin) [25]. If S. aureus formed cobiofilms with C. albicans on a filter membrane after 24-h maturation, there was a significant increase in expression of hla (7.06 ± 2.19 fold increase) and hlgB (8.12 ± 2.64 fold increase) in SC5314 group but not in hyphae-defective HLC54 group (hla: 1.54 ± 0.30 and hlgB: 2.09 ± 0.81) (Figure 5).…”

The Arginine Biosynthesis Pathway of Candida albicans Regulates Its Cross-Kingdom Interaction with Actinomyces viscosus to Promote Root Caries

“… Streptococcus gordonii could also promote C. albicans biofilm formation and hyphal development ( 17 ). C. albicans and Staphylococcus aureus synergistically interacted to promote pathogenic potential, increase resistance to antibiotics and help Candida circumvent the host immune system ( 27 , 28 ). However, the key pathways by which C. albicans regulates its interactions with oral bacteria are still unclear.…”

The immature gut : Microbes and nutrition orchestrate maturation of the preterm gastrointestinal tract

“…Most mutualistic interactions have been observed in the oral and vaginal environments between C. albicans and various Streptococcus species in mixed biofilms 61,[193][194][195] . Bacteria and fungi co-occur in mixed biofilms providing extra protection against host immune responses compared to monoculture biofilms [195][196][197][198][199] . On the one hand, bacteria are protected by a fungal polysaccharide matrix and become more resistant to antibacterial compounds [195][196][197]200 .…”

“…Archaea and viruses additionally need to be accounted for to obtain a holistic ecological perspective of the human intestine. Researching such interkingdom interactions in the (infant) intestine would be especially relevant in a clinical setting, as bacteria and fungi may interact synergistically in mixed biofilms to increase antimicrobial recalcitrance and protection against host immune responses [195][196][197][198][199] . Subsequent formation of mixed biofilms on indwelling medical devices-such as nasogastric enteral feeding tubes-could become a reservoir of microbes and antibiotic resistance genes that are introduced into the preterm gastrointestinal tract upon feeding, thereby forming a risk of microbial dysbiosis and infections [463][464][465] .…”