Listening to microbial conversations

The microbial world contains a vast and untapped reservoir of genetic diversity that could be used for the production of novel, biologically active molecules or to develop new strategies to manipulate the activities of microbial consortia. However, we need to understand how microbial species interact and communicate with each other in order to manipulate their interactions. With pyrosequencing and other technological breakthroughs, we are beginning to understand ‘who is there’ and ‘what they are capable of doing’. What we need to do is to get better at understanding ‘what they are doing’ to exploit fully the diversity of the microbial world. We have made great strides in computational approaches that allow us to assign putative functions to many of the genes present in microbial genomes; but, even with these tools, many coding regions lack functional assignments. Many genomes contain ‘cryptic’ or ‘orphan’ gene clusters with the potential to produce novel and structurally complex chemicals (Challis, 2008; Fischbach et al., 2008). These chemicals do not have ‘housekeeping’ functions, but probably function as signals mediating interactions among microorganisms and between microorganisms and eukaryotes (Straight et al., 2006; Dietrich et al., 2008; Fischbach et al., 2008). These studies suggest that microbes are carrying on a conversation with each other. We must listen to and translate this conversation to understand how microbial species interact with each other. Once we understand what microbes are saying and why, then we can manipulate the conversations. We should not be surprised that microbes converse because we know that microbial species work in teams or guilds. These interspecies interactions must be coordinated, which means that there must be specific signals. In the future, we will have a variety of high‐throughput tools to identify how microbial populations respond to each other and what molecules are used. Such approaches may be analogous to microarray technologies such as GeoChip (He et al., 2007). Computational approaches will be available to identify the key regulatory components that receive, translate and transmit the signal to action. As the regulatory networks are defined, we will be able to identify the input chemical stimulus, its receptor and how the signal is transmitted within the cell. Bioengineers can then construct multi‐component systems from libraries of standard interchangeable parts engineered from the components identified during the ecological screening process. Professor Endy and his colleagues (Canton et al., 2008) have developed BioBrick (http://partsregistry.org/), a standard biological parts inventory, which includes protein coding sequences and regulatory elements for gene expression and signalling and have defined quantitative measures of performance that will allow bioengineers to use these parts reliably. Future efforts will certainly expand on the parts and chassis (organisms) available for manipulation. By understanding how biosynthetic genes change, move about and recombine, we can understand the processes that generate small‐molecule diversity. Once we understand the microbial conversations, we will have the ability to manipulate the response of a specific microbe or of microbial communities. We will be able to identify signals to turn on gene systems to produce new biologically active molecules that could be used as antibiotics or anticancer drugs. Additionally, we may identify signals to turn on specific functions in complex communities. Understanding why microorganisms make biosurfactants may provide an approach to turn biosurfactant production on in oil wells to enhance oil recovery (Youssef et al., 2007). Alternatively, we should be able to disrupt the microbial conversation to prevent unwanted interactions involved in disease or corrosion.