Abstract
Streptococcus mutans activates multiple cellular processes in response to the formation of a complex between comX-inducing peptide (XIP) and the ComR transcriptional regulator. Bulk phase and microfluidic experiments previously revealed that ComR-dependent activation of comX is altered by pH and by carbohydrate source. Biofilm formation is a major factor in bacterial survival and virulence in the oral cavity. Here, we sought to determine the response of S. mutans biofilm cells to XIP during different stages of biofilm maturation. Using flow cytometry and confocal microscopy, we showed that exogenous addition of XIP to early biofilms resulted in robust comX activation. However, as the biofilms matured, increasing amounts of XIP were required to activate comX expression. Single-cell analysis demonstrated that the entire population was responding to XIP with activation of comX in early biofilms, but only a sub-population was responding in mature biofilms. The sub-population response of mature biofilms was retained when the cells were dispersed and then treated with XIP. The proportion and intensity of the bi-modal response of mature biofilm cells was altered in mutants lacking the Type II toxins MazF and RelE, or in a strain lacking the (p)ppGpp synthase/hydrolase RelA. Thus, competence signaling is markedly altered in cells growing in mature biofilms, and pathways that control cell death and growth/survival decisions modulate activation of comX expression in these sessile populations.
Highlights
Streptococcus mutans is a principal microorganism contributing to the ubiquitous oral infectious disease dental caries (Loesche, 1986)
We further investigated the origins of phenotypic heterogeneity in biofilms by exploring whether gene products that govern programmed cell death (PCD) and/or growth and survival decisions influence XIP signaling
green fluorescent protein (GFP) expression from the PcomXgfp promoter fusion was observable within 1 h after induction with 200 nM XIP, whereas GFP fluorescence was only detected after 3 h when 50 nM XIP was added to the growth medium
Summary
Streptococcus mutans is a principal microorganism contributing to the ubiquitous oral infectious disease dental caries (Loesche, 1986). Perturbations of the environment by the diet, host factors, and endogenous activities of oral biofilms induce changes in microbial composition and behaviors that foster the development of oral infectious diseases. The initiation and progression of dental caries in particular is associated with increases in the proportions of acid tolerant, acidproducing bacteria that rapidly metabolize carbohydrates, leading to repeated acidification of oral biofilms. The acidic environment created demineralizes the tooth while concurrently selecting for organisms that are better adapted to growth at low pH. Biofilm formation, growth and metabolism of carbohydrates at low pH, and the ability to respond rapidly to fluctuations in carbohydrate source and availability are attributes of S. mutans that are essential for its contributions to the initiation and progression of dental caries (Lemos et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
