A biofilm is a surface-associated population of microbes that is embedded in a cement of extracellular compounds. This cement is known as matrix. The two main functions of matrix are to protect cells from their surrounding environment, preventing drugs and other stresses from penetrating the biofilm, and to maintain the architectural stability of the biofilm, acting as a glue to hold the cells together. The presence of matrix is a contributing factor to the high degree of resistance to antimicrobial drugs observed in biofilms. Because biofilms have a major impact on human health, and because matrix is such a pivotal component of biofilms, it is important to understand how the production of matrix is regulated.
A group of researchers has identified a novel regulatory gene network that plays an important role in the spread of common, and sometimes deadly, fungus infections. The new findings establish the role of Zap1 protein in the activation of genes that regulate the synthesis of biofilm matrix. Candida albicans is a fungus, more specifically a yeast, which approximately 80 percent of people have in their gastrointestinal and genitourinary tract with no ill effects. However, at elevated levels it can cause non-life threatening conditions like thrush and yeast infections. C. albicans infection becomes much more serious, and can be lethal in those with compromised immune systems who have an implantable medical device such as a pacemaker or artificial joint, or who use broad-spectrum antibiotics. Central to such infections is the biofilm – a population of microbes, in this case C. albicans cells, joined together to form a sheet of cells. The cells in the biofilm produce extracellular components such as proteins and sugars, which form a cement-like matrix. This matrix serves to protect the cells of the biofilm, preventing drugs and other stressors from attacking the cells while acting as a glue that holds the cells together. By doing this, the matrix provides an environment in which yeast cells in the biofilm can thrive, promoting infection and drug resistance.
Biofilms have a major impact on human health and matrix is such a pivotal component of biofilms. It is important to understand how the production of matrix is regulated. In the study, the scientists found that the zinc-responsive regulatory protein Zap1 prevents the production of soluble beta-1,3 glucan, a sugar that is a major component of matrix. They also identified other genes whose expression is controlled by Zap1, called Zap1 target genes. They found that these genes encode two types of enzymes, glucoamylases and alcohol dehydrogenases, which both govern the production and maturation of matrix components. Understanding this novel regulatory gene network gives us insight into the metabolic processes that contribute to biofilm formation, and the role the network plays in infection. By better understanding the mechanisms by which biofilms develop and grow, we can start to look at targets for combating infection.
Biofilm Matrix Regulation by Candida albicans Zap1. 2009 PLoS Biol 7(6): e1000133 doi:10.1371/journal.pbio.1000133
A biofilm is a surface-associated population of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms are a major natural growth form of microorganisms and the cause of pervasive device-associated infection. This report focuses on the biofilm matrix of Candida albicans, the major fungal pathogen of humans. We report here that the C. albicans zinc-response transcription factor Zap1 is a negative regulator of a major matrix component, soluble b-1,3 glucan, in both in vitro and in vivo biofilm models. To understand the mechanistic relationship between Zap1 and matrix, we identified Zap1 target genes through expression profiling and full genome chromatin immunoprecipitation. On the basis of these results, we designed additional experiments showing that two glucoamylases, Gca1 and Gca2, have positive roles in matrix production and may function through hydrolysis of insoluble b-1,3 glucan chains. We also show that a group of alcohol dehydrogenases Adh5, Csh1, and Ifd6 have roles in matrix production: Adh5 acts positively, and Csh1 and Ifd6, negatively. We propose that these alcohol dehydrogenases generate quorum-sensing aryl and acyl alcohols that in turn govern multiple events in biofilm maturation. Our findings define a novel regulatory circuit and its mechanism of control of a process central to infection.
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Gathering and sharing of information is extremely important in human society. Especially in times of war, the difference between victory and defeat can depend on the ability to obtain, encrypt, and share information, and sophisticated systems have been developed for exactly this purpose. Similarly, in their constant battles with competitors and the host immune system, (opportunistic) microbial pathogens have developed sophisticated cell–cell communication systems termed quorum sensing (QS) that allow exchange of critical information. In return, competing microbes, as well as the host immune system, have developed means to intercept and decode these messages. The information obtained by this molecular espionage is used for their benefit, either to win the war (microbe against microbe), or to prepare for an upcoming battle (microbe against immune system).
