A complex relationship: the interaction among symbiotic microbes, invading pathogens, and their mammalian host

Abstract

Symbiosis between microbes and their mammalian host is vital to maintaining homeostasis. Symbiotic microbes within the gastrointestinal tract provide an array of benefits to the host, including promotion of host immunity. A coordinated effort of the host and symbiotic microbes deters the colonization and survival of many invading pathogens. However, pathogens have devised strategies to overcome these mechanisms. Furthermore, some pathogens can hijack host hormones and bacterial autoinducers to induce virulence traits. Intra- and inter-species (bacteria/bacteria) and interkingdom (bacteria/host) communication orchestrates the complex relationship among symbiotic microbes, invading pathogens, and their mammalian host. Insight into this communication will provide a foundation for the development of targeted antimicrobial therapies.

Figure 1

The LasI/LasR quorum sensing system in P. aeruginosa. (A) LasI synthesizes 3-oxo-C12 HSL, an AHL that freely diffuses across the bacterial membrane at low cell density; (B) At high cell density, 3-oxo-C12 HSL diffuses back into the cell, binds to the transcriptional activator LasR, and induces the expression of virulence genes.

Figure 2

The epinephrine/norepinephrine/AI-3 inter-kingdom signaling system. (A) The histidine sensor kinase QseC senses the mammalian hormones epinephrine and norepinephrine and the bacterial autoinducer AI-3. Activation of QseC stimulates an intrinsic autophosphorylation activity, allowing QseC to then transfer its phosphate group to one of three response regulators: QseB, QseF, and KdpE. The response regulators differentially regulate gene expression. (B) Epinephrine and norepinephrine bind to mammalian adrenergic receptors and play a role in smooth muscle control, submucosal blood flow, and chloride and potassium secretion. It remains unknown if AI-3 can bind to mammalian adrenergic receptors and alter mammalian function.