Affiliation:
1. Dental Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1G6
2. Department of Oral Microbiology, Malmö University, S-21421 Malmö, Sweden
Abstract
ABSTRACT
The abilities of
Streptococcus mutans
to form biofilms and to survive acidic pH are regarded as two important virulence determinants in the pathogenesis of dental caries. Environmental stimuli are thought to regulate the expression of several genes associated with virulence factors through the activity of two-component signal transduction systems. Yet, little is known of the involvement of these systems in the physiology and pathogenicity of
S. mutans
. In this study, we describe a two-component regulatory system and its involvement in biofilm formation and acid resistance in
S. mutans
. By searching the
S. mutans
genome database with tblastn with the HK03 and RR03 protein sequences from
S. pneumoniae
as queries, we identified two genes, designated
hk11
and
rr11
, that encode a putative histidine kinase and its cognate response regulator. To gain insight into their function, a PCR-mediated allelic-exchange mutagenesis strategy was used to create the
hk11
(Em
r
) and
rr11
(Em
r
) deletion mutants from
S. mutans
wild-type NG8 named SMHK11 and SMRR11, respectively. The mutants were examined for their growth rates, genetic competence, ability to form biofilms, and resistance to low-pH challenge. The results showed that deletion of
hk11
or
rr11
resulted in defects in biofilm formation and resistance to acidic pH. Both mutants formed biofilms with reduced biomass (50 to 70% of the density of the parent strain). Scanning electron microscopy revealed that the biofilms formed by the mutants had sponge-like architecture with what appeared to be large gaps that resembled water channel-like structures. The mutant biofilms were composed of longer chains of cells than those of the parent biofilm. Deletion of
hk11
also resulted in greatly diminished resistance to low pH, although we did not observe the same effect when
rr11
was deleted. Genetic competence was not affected in either mutant. The results suggested that the gene product of
hk11
in
S. mutans
might act as a pH sensor that could cross talk with one or more response regulators. We conclude that the two-component signal transduction system encoded by
hk11
and
rr11
represents a new regulatory system involved in biofilm formation and acid resistance in
S. mutans
.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
187 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献