Hi Neighbor - Have some of my glycerol

Metabolic exchange between microbes is important for community development. One of the newly identified interactions between oral commensals involves glycerol, leading to relevant phenotypes that might support oral health.
Published in Microbiology
Hi Neighbor - Have some of my glycerol

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"Biofilm, city of microbes" (1) was one of the defining reviews for me as a new post-doc, quite a while ago. It made me realize that my path forward as a microbiologist has to be in the context of microbial ecology. Microbes do not dwell alone, quite the contrary, they thrive when others are around, like to chat, share, work together and sometimes fight with neighboring species co-inhabiting the biofilm. My group is interested in these interspecies interactions that are ultimately responsible for species distribution in the developing biofilm and determine overall biofilm architecture. The species distribution inside the biofilm is also intimately linked to the ability of a biofilm to cause disease or as even more important, but vastly understudied, support health. Our area of research is the oral biofilm.

 We previously reported that two abundant and oral health associated species, Streptococcus sanguinis and Corynebacterium durum have a close relationship through the production of membrane vesicle and fatty acids leading to S. sanguinis chain elongation and overall increased fitness supporting their commensal state (2) and Fig 1.  

Fig. 1: Mixed species cultures of S. sanguinis and C. durum lead to a striking chain elongation phenotype of S. sanguinis. The phenotype can also be induced by supplying C. durum membrane vesicles (MV's) to S. sanguinis cultures. MVs are visible on biofilm grown C. durum and can be easily purified (2).

To further understand the relationship and define the molecular mechanisms that lead to the observed chain elongation phenotype, we performed global transcriptome analysis of the co-cultures to identify differentially expressed genes in S. sanguinis. Two operons caught our interest, the glp-operon encoding important genes for glycerol metabolism and the pil-operon responsible for type IV pilus formation on the surface of S. sanguinis.

In a series of experiments, we demonstrate that C. durum is secreting glycerol, which can subsequently  be utilized by S. sanguinis for growth and fitness. and S. sanguinis can utilize the secreted glycerol from C. durum supernatants for growth. The metabolism of glycerol requires functional expression of S. sanguinis glp-operon genes, and deletion of the glycerol kinase GlpK, a central enzyme involved in glycerol metabolism, affects chain elongation. Glycerol and glycerol containing compounds, such as lipids, are among the most abundant organic compounds that can be utilized as alternative carbon/energy sources for many host adapted bacteria, including many other oral bacteria. The questions that comes to mind is how does C. durum ensure that its secreted glycerol would benefit S. sanguinis the most, and how can complex, large molecules e.g. glycerol and lipids be properly secreted and utilizedso that both can form the synergistic commensal entity that might support oral health? This is where the pil-operon enters the stage. The pil-operon is down regulated during co-culture resulting decreased surface display of pili (Fig. 2).  

Fig. 2: (Left) The involvement of glycerol in inducing S. sanguinis chain elongation, and a requirement of S. sanguinis GlpK for bacterial glycerol metabolism. (Right) Different capability of type IV pilus formation in both S. sanguinis SK36 and SK408 strains, and the down-regulatory effect of C. durum on S. sanguinis type IV pili. 

Bacterial type IV pili are known to be essential for various functions influencing microbial ecology, including adhesion, bacterial-bacterial and bacterial-host interactions. Surprisingly, in S. sanguinis (at least in some strains) type IV pili are also responsible for twitching/gliding motility. Thus, a C. durum dependent repression of pilus gene expression seems to favor the commensal state of S. sanguinis since it would abolish its ability to move away. It might also decrease its ability to adhere to other species thus aiding in the close interaction of both providing the ideal commensal relationship.

Why is research into commensals and "molecular commensalism" important?

Polymicrobial diseases affecting mucosal surfaces do not strictly adhere to Koch’s postulates, as no single invading species can be identified as a causative agent. Consequently, eliminating a single organism from the body is a largely ineffective strategy to resolve such complex diseases these types of diseases. A holistic approach may be useful for identifying mechanisms to support or strengthen molecular commensalism (3) of our microbiomes in order to avert sickness or at least understand these organisms’ roles in supporting health and homeostasis.


(1) Watnick P, Kolter R. Biofilm, city of microbes. J Bacteriol. 2000 May;182(10):2675-9. doi: 10.1128/JB.182.10.2675-2679.2000. PMID: 10781532; PMCID: PMC101960.

(2) Treerat P, Redanz U, Redanz S, Giacaman RA, Merritt J, Kreth J. Synergism between Corynebacterium and Streptococcus sanguinis reveals new interactions between oral commensals. ISME J. 2020 May;14(5):1154-1169. doi: 10.1038/s41396-020-0598-2. Epub 2020 Feb 4. PMID: 32020052; PMCID: PMC7174362.

(3) Kreth J, Giacaman RA, Raghavan R, Merritt J. The road less traveled - defining molecular commensalism with Streptococcus sanguinis. Mol Oral Microbiol. 2017 Jun;32(3):181-196. doi: 10.1111/omi.12170. Epub 2016 Sep 20. PMID: 27476770; PMCID: PMC5288394.

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  • The ISME Journal The ISME Journal

    This journal covers the diverse and integrated areas of microbial ecology and encourages contributions that represent major advances for the study of microbial ecosystems, communities, and interactions of microorganisms in the environment.