Affiliation:
1. Department of Bacteriology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
2. Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
3. Project Research Centre for Oral Infectious Diseases, Hiroshima University, Hiroshima, Japan
4. Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan
Abstract
ABSTRACT
Streptococcus mutans
is a cariogenic bacterium that produces a variety of bacteriocins and retains resistance to these bacteriocins. In this study, we investigated the susceptibility of 127
S
.
mutans
strains to nukacins produced by
Staphylococcus
spp., which are commensal bacteria in humans. We detected diverse susceptibilities among strains. Nineteen strains had a disrupted LctF (type I), which is responsible for nukacin susceptibility, whereas the remaining 108 strains had an intact LctF (type II) and displayed resistance to nukacins. However, the type I strains still showed resistance to nukacins to some extent. Interestingly, 18/19 (94.7%) type I strains carried a
mukA-T
locus, which is related to the synthesis of mutacin K8, and
mukFEG
, an ABC transporter. In contrast, among type II strains, only 6/108 strains (5.6%) had both the
mukA-T
locus and
mukFEG
, 19/108 strains (17.6%) carried only
mukFEG
, and 83/108 strains (76.9%) harbored neither
mukA-T
nor
mukFEG
. We also found that MukF had two variants: 305 amino acids (type α) and 302 amino acids (type β). All type I strains showed a type α (MukFα), whereas most type II strains with
mukFEG
(22/25 strains) had a type β (MukFβ). Then, we constructed a
mukFEG
-deletion mutant complemented with MukFαEG or MukFβEG and found that only MukFαEG was involved in nukacin resistance. The nukacin resistance capability of type II-LctFEG was stronger than that of MukFαEG. In conclusion, we identified a novel nukacin resistance factor, MukFEG, and either LctFEG or MukFEG was active in most strains via genetic polymorphisms depending on
mukA-T
genes.
IMPORTANCE
Streptococcus mutans
is an important pathogenic bacterium not only for dental caries but also for systemic diseases.
S. mutans
is known to produce a variety of bacteriocins and to retain resistance these bacteriocins. In this study, two ABC transporters, LctFEG and MukFEG, were implicated in nukacin resistance and each ABC transporter has two subtypes, active and inactive. Of the two ABC transporters, only one ABC transporter was always resistant, while the other ABC transporter was inactivated by genetic mutation. Interestingly, this phenomenon was defined by the presence or absence of the mutacin K8 synthesis gene region, one of the bacteriocins of
S. mutans
. This suggests that the resistance acquisition is tightly controlled in each strain. This study provides important evidence that the insertion of bacteriocin synthesis genes is involved in the induction of genetic polymorphisms and suggests that bacteriocin synthesis genes may play an important role in bacterial evolution.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Publisher
American Society for Microbiology