Polybacterial human disease: the ills of social networking

Abstract

Polybacterial diseases involve multiple organisms that act collectively to facilitate disease progression. Although this phenomenon was highlighted early in the 20th century, recent technological advances in diagnostics have led to the appreciation that many infections are far more complex than originally believed. Furthermore, it is apparent that although most treatments focus on the dominant bacterial species in an infection, other microbes, including commensals, can have a profound impact on both the response to therapy and virulence. Very little is known about the molecular mechanisms that underpin interactions between bacteria during such infections. Here, we discuss recent studies identifying and characterizing mechanisms of bacterial interaction and the biological processes they govern during certain diseases. We also highlight how possible strategies for targeting these interbacterial interactions may afford a route towards development of new therapies, with consequences for disease control.

Keywords: cell–cell signaling; infection; metatranscriptomics; polybacterial disease; polymicrobial infection; synergy.

Figure 1

Schematic illustrating potential bacterial interspecies interactions. Bacteria can influence other cells in a community through both chemical (top) and physical interactions (bottom). Chemical interactions include the production and perception of specific signal molecules such as diffusible signal factor (DSF) and autoinducer-2 (AI-2), which benefit both the producer and the receiver strain. The cross-feeding of metabolites between members of a community allows growth on complex carbon sources, and can also elicit responses distinct from metabolism, as a means of surveying the bacterial community. H₂O₂ and peptidoglycan are two examples of interspecies cues that elicit beneficial responses in the receiving species. Physical interactions between cells include those involved in formation of biofilms, which protect cells from stresses such as antibiotics and host immunity. Formation of mixed-species biofilms involves receptor and adhesin-mediated co-aggregation, interaction of other surface appendages such as pili and fimbriae, and the regulated secretion of an extracellular matrix in which surface structures become embedded. Contact-dependent interactions can also be antagonistic, as seen with type VI secretion in which toxins are translocated into neighboring cells.