Medically important bacterial–fungal interactions

Key Points This Review focuses on the mechanisms and clinical importance of the bacterial–fungal interactions that occur on or in the human body. Bacteria and fungi can interact in several ways, including physical interactions by direct cell–cell contact, chemical interaction through the secretion of small molecules that are often involved in quorum sensing, environmental modifications such as pH changes, use of metabolic by-products and alterations in host responses. A range of mammalian and non-mammalian models of infection are now available for the study of mixed bacterial–fungal infections. Several Gram-negative pathogens are capable of killing Candida albicans and inhibiting filament formation, including Pseudomonas aeruginosa , Acinetobacter baumannii , Burkholderia cepacia and Salmonella enterica subsp. enterica serovar Typhimurium. This is predominantly mediated through the secretion of small molecules, such as quorum-sensing molecules and other known secretory virulence factors (namely, phospholipase C and phenazines for P. aeruginosa ). Oral streptococci have adapted to adhere to C. albicans in the human mouth, and this seems to be mediated through polysaccharide receptors on the bacterial surface. Such co-aggregation is important in the pathogenesis of many oral diseases. C. albicans mounts a defence against these bacterial predators through the secretion of its quorum-sensing molecule farnesol. This molecule can affect bacterial production of virulence factors, viability and susceptibility to antibacterials. Limited study has been dedicated to understanding the host responses to polymicrobial infections. Recent work in mice suggests that immune responses to a bacterial–fungal infection may be directed preferentially towards a bacterial-type response mediated by T helper 1 cells. The human body plays host to interactions between a diverse range of microorganisms, including bacteria and fungi. In this Review, Mylonakis and colleagues describe the characteristics of medically important bacterial–fungal interactions and highlight how imbalances in these interactions can contribute to human disease. Whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. The interactions between these taxonomically diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. Human disease can develop from an imbalance between c