Abstract
Despite their clinical significance and substantial human health burden, fungal infections remain relatively under-appreciated. The widespread overuse of antibiotics and the increasing requirement for indwelling medical devices provides an opportunistic potential for the overgrowth and colonization of pathogenic Candida species on both biological and inert substrates. Indeed, it is now widely recognized that biofilms are a highly important part of their virulence repertoire. Candida albicans is regarded as the primary fungal biofilm forming species, yet there is also increasing interest and growing body of evidence for non-Candida albicans species (NCAS) biofilms, and interkingdom biofilm interactions. C. albicans biofilms are heterogeneous structures by definition, existing as three-dimensional populations of yeast, pseudo-hyphae, and hyphae, embedded within a self-produced extracellular matrix. Classical molecular approaches, driven by extensive studies of laboratory strains and mutants, have enhanced our knowledge and understanding of how these complex communities develop, thrive, and cause host-mediated damage. Yet our clinical observations tell a different story, with differential patient responses potentially due to inherent biological heterogeneity from specific clinical isolates associated with their infections. This review explores some of the recent advances made in an attempt to explore the importance of working with clinical isolates, and what this has taught us.
Highlights
Despite their clinical significance and substantial human health burden, fungal infections remain relatively under-appreciated
When this was subsequently assessed at Candida species level, survival analysis demonstrated significantly higher survival rates for patients with C. albicans associated line removal compared to no removal, with no differences observed in non-Candida albicans species (NCAS) [51]
Despite C. albicans being regarded as the principal biofilm forming pathogen of the genus, there has been a steady flow of research looking at non-albicans biofilms over the last decade
Summary
Classical molecular microbiological approaches suggest that deletion or over expression of particular genes enables us to definitively deduce their function. Reinforced by structural biology studies, these tactics allow us to deduce the structure/function of particular proteins within the context of a microbes pathogenic ability. This assumes that molecular manipulations do not have any pleiotropic effects, nor does this take into account inherent biological heterogeneity that bears itself amongst a range of clinical isolates (Figure 1). Environmental stressors stressors can can alsostimulate stimulatebiofilm biofilmformation, formation,and andthese these include availability include thethe availability of of nutrients, temperature, Dashed arrows represent different that associate with nutrients, temperature, and and pH. Dashed arrows represent different factorsfactors that associate with biofilm biofilm formation
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