Candida albicans and Staphylococcus aureus Pathogenicity and Polymicrobial Interactions: Lessons beyond Koch’s Postulates

Abstract

While Koch’s Postulates have established rules for microbial pathogenesis that have been extremely beneficial for monomicrobial infections, new studies regarding polymicrobial pathogenesis defy these standards. The explosion of phylogenetic sequence data has revolutionized concepts of microbial interactions on and within the host. However, there remains a paucity of functional follow-up studies to delineate mechanisms driven by such interactions and how they shape health or disease. That said, one particular microbial pairing, the fungal opportunist Candida albicans and the bacterial pathogen Staphylococcus aureus, has received much attention over the last decade. Therefore, the objective of this review is to discuss the multi-faceted mechanisms employed by these two ubiquitous human pathogens during polymicrobial growth, including how they: establish and persist in inter-Kingdom biofilms, tolerate antimicrobial therapy, co-invade host tissue, exacerbate quorum sensing and staphylococcal toxin production, and elicit infectious synergism. Commentary regarding new challenges and remaining questions related to future discovery of this fascinating fungal–bacterial interaction is also provided.

Inhibition of Mixed Biofilms of Candida albicans and Methicillin-Resistant Staphylococcus aureus by Positively Charged Silver Nanoparticles and Functionalized Silicone Elastomers

“…Together, C. albicans and S. aureus are responsible for a majority of opportunistic nosocomial infections [ 9 , 15 ], and they are often co-isolated from a host [ 13 ]. Frequently, these polymicrobial infections are associated with the formation of mixed biofilms in catheters and other indwelling devices, where C. albicans and S. aureus display a symbiotic relationship [ 16 , 30 ]. For example, MRSA resistance is enhanced within the mixed biofilm due to the protection by the fungal extracellular matrix, more specifically the secreted β-1,3-glucan component [ 9 ], and the invasive behavior of MRSA is facilitated by C. albicans leading to invasive infection in co-colonized patients.…”

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy

“…It is estimated that more than 80% of microbial infections are caused by microbes growing as biofilms (Romling and Balsalobre, 2012 ), and therefore their determination of their susceptibility to antimicrobial agents, including AMP, is of paramount importance when developing novel antimicrobial agents. An increasing understanding of biofilm infections has led to the appreciation that many infections are polymicrobial in nature and may contain diverse species of bacteria, fungi and viruses (Peters et al, 2012 ; Wolcott et al, 2013 ; Mihai et al, 2015 ; Todd and Peters, 2019 ) and a number of models of polymicrobial biofilms have recently been developed (Gabrilska and Rumbaugh, 2015 ). Polymicrobial biofilms are of relevance in many infections, including chronic wound infections (Clinton and Carter, 2015 ), CF lung infections (Lopes et al, 2015 ), bacterial vaginosis (Jung et al, 2017 ) and medical device-associated infections (Wi and Patel, 2018 ).…”

Quorum Sensing and Toxin Production in Staphylococcus aureus Osteomyelitis: Pathogenesis and Paradox

“…In other disease models, co-infecting bacterial species, including Pseudomonas aeruginosa, augment S. aureus agr expression [106]. Cross-kingdom Agr interactions were also identified in polymicrobial infections with S. aureus and fungal species, Candida albicans [107]. However, further studies are necessary to elucidate the polymicrobial interactions that occur specifically during osteomyelitis and to determine how these interactions impact disease pathogenesis.…”