Calling all hosts: Bacterial communication in situ.

Bacteria are cosmopolitan organisms that in recent years have demonstrated many roles in maintaining host equilibrium. In this review, we discuss three roles bacteria can occupy in a host: pathogenic, symbiotic, and transient, with a specific focus on how bacterial small molecules contribute to homeostasis or dysbiosis. First, we will dissect how small molecules produced by pathogenic bacteria can be used as a source for communication during colonization and as protection against host immune responses. The ability to achieve a higher level of organization through small molecule communication gives pathogenic bacteria an opportunity for increased virulence and fitness. Conversely, in symbiotic relationships with hosts, small molecules are used in the initial acquisition, colonization, and maintenance of this beneficial population. Chemical signals can come from both the host and symbiont, and it is often observed that these interKingdom symbioses result in coevolution of both species involved. Furthermore, the transition from transient to commensal or opportunistic likely relies on molecular mechanisms. The small molecules utilized and produced by transient bacteria are desirable for both the immune and nutritional benefits they provide to the host. Finally, the advantages and disadvantages of modern analytical techniques that are available to researchers in order to study small molecules in situ is an important aspect of this review. It is our opinion that small molecules produced by bacteria are central to many biological processes and a larger focus on uncovering the function and identity of these small molecules is required to gain a deeper understanding of host-microbe associations.