Talking to Themselves: Autoregulation and Quorum Sensing in Fungi

Abstract

Extracellular autoinducing compounds in the supernatants of microbial cultures were first recognized for their roles in the induction of genetic competence in gram-positive bacteria (17,94) and in the regulation of light production in marine vibrios (60). In 1994, this form of population-level regulation in microbes was dubbed "quorum sensing" since it enabled bacterial cells to chemically measure the density of the surrounding population (18). Subsequently, many examples of cell densitydependent regulation by extracellular factors have been found in diverse microorganisms. The widespread incidence of diverse quorum-sensing systems strongly suggests that regulation in accordance with cell density is important for the success of microbes in many environments (see references 25 and 95 for reviews).Cell density-dependent regulatory networks in microorganisms generally control processes that involve cell-cell interactions, such as group motility (10, 37) and the formation of multicellular structures (67,93,95). In a wide array of environmental and medically relevant bacteria, the development, maintenance, and dispersion of multicellular, surface-associated biofilms are in part controlled by quorum-sensing regulatory pathways (for reviews, see references 67 and 93). The uptake of extracellular DNA is often regulated in accordance with cell density presumably to enhance the chances of taking up DNA from closely related strains. For some bacteria, a link between the competence and biofilm formation has been established (69, 93). Both pathogens and symbionts that live in association with plant or animal hosts often use quorum sensing to regulate factors involved in microbe-host interactions (20,86,96). Quorum-sensing regulation may allow host-associated microbes to delay detection until an effective population has formed in the appropriate niche within the host.Recently, it has become apparent that fungi, like bacteria, also use quorum regulation to affect population-level behaviors such as biofilm formation and pathogenesis. Considering the extent to which quorum-sensing regulation controls important processes in many distantly related bacterial genera, it is not surprising that cell density-dependent regulation also appears to be prevalent in diverse fungal species. Because fungal quorum sensing has been most extensively studied in Candida albicans, a dimorphic opportunistic pathogen, the majority of this review focuses on the details of quorum-sensing regulation in this fungus. A discussion of other fungi that appear to use quorum-sensing regulation and the identities of other known fungal signaling molecules are presented, and potential connections between mating in fungi and cell density-dependent regulation are explored. The review will conclude with points relating to the ecology of quorum sensing and a discussion of quorum-sensing networks as potential targets for antifungal therapies.

Saprophytic growth of the alder rust fungus Melampsoridium hiratsukanum on artificial media

“…Such a cell-density regulatory pathway is thought to be mediated by small, diffusible signal molecules (exo-factors) secreted by the rust propagules, and they were among the first cases of cell-to-cell communication in fungi to be reported (Epstein et al 1985;Moricca & Ragazzi 2001). This type of cooperative behaviour is now widely known as 'quorum sensing' (Hogan 2006). We hypothesise that the collective production of quorum-signalling compounds benefits surrounding cells in the local spore population, causing greater spore germination, which later leads first to hyphal aggregations and then to the growth of visible mycelial initials in the agar medium.…”

Pathogenesis of Polymicrobial Biofilms

“…Although much of what we understand today came from the study of single species biofilm, it is now clear that in the natural and clinical environments, most biofilms are likely to consist of consortia of species that influence each other in synergistic and antagonistic manners [4,8,20]. However, limited studies have specifically addressed interactions within multi species biofilms and particularly interactions between bacteria and fungi, which are often found together in a myriad of environments [16,[21][22][23]. Although the area of research exploring interkingdom interactions in biofilm is still in its infancy, there is increasing awareness of their clinical implications in the host particularly between the fungal pathogen Candida albicans and various bacterial species (for detailed description of some of these interactions within the context of human disease, the reader is referred to two recent reviews) [22,23].…”

“…In a biofilm environment, microbial species are highly interactive and employ a range of cell-to-cell communication or 'quorum sensing' systems [16][17][18]. This phenomenon for promoting collective behavior with in a population is important in ensuring survival and propagation by enhancing access to nutrients and niches, as well as providing protection [4,5,19].…”

Microsatellite Typing of Catheter-Associated Candida albicans Strains

“…In their natural habitat microorganisms including yeasts are mostly organized in biofilm ecosystems which are often ´multicultural´, made not only of yeasts but also of bacteria (El-Aziz et al, 2004;López-Ribot, 2005;Ramage et al, 2005;Nobile et al, 2006). The possibility to adhere to a surface is a very important factor for the development of fungal (Hogan, 2006;Verstrepen & Klis, 2006) and bacterial biofilms (Dolan, 2001). …”