Abstract.
Streptococcus mutans is a bacterial cause of dental caries that is resistant to bacitracin. The aim of this study was to elucidate the mbrABCD-related bacitracin resistance mechanism of S. mutans. Transcriptome data demonstrated that the expression levels of 33 genes were induced more than twofold by bacitracin. Fourteen genes were selected from the upregulated genes, and defective mutants of these genes were constructed for measurement of their sensitivity to bacitracin. Among the mutants, only the mbrA- or mbrB-deficient mutants exhibited 100- to 121-fold greater sensitivity to bacitracin when compared with the wild-type strain. Moreover, knockout of the mbrC and mbrD genes abolished the bacitracin-induced mbrAB upregulation. These results suggest that both mbrC and mbrD are required for mbrAB upregulation that confers the bacitracin-resistant phenotype on S. mutans.
[Supplementary Table: available only at http://dx.doi.org/10.1254/jphs.11052SC]
Keywords: Streptococcus mutans, bacitracin, bacitracin resistance
References
- 1.Anker HS, Johnson BA, Goldberg J, Meleney FL. Bacitracin: methods of production, concentration, and partial purification, with a summary of the chemical properties of crude bacitracin. J Bacteriol. 1948;55:249–255. [PMC free article] [PubMed] [Google Scholar]
- 2.Azevedo EC, Rios EM, Fukushima K, Campos-Takaki GM. Bacitracin production by a new strain of Bacillus subtilis. Extraction, purification, and characterization. Appl Biochem Biotechnol. 1993;42:1–7. doi: 10.1007/BF02788897. [DOI] [PubMed] [Google Scholar]
- 3.Chapnick EK, Gradon JD, Kreiswirth B, Lutwick LI, Schaffer BC, Schiano TD. Comparative killing kinetics of methicillin-resistant Staphylococcus aureus by bacitracin or mupirocin. Infect Control Hosp Epidemiol. 1996;17:178–180. doi: 10.1086/647270. [DOI] [PubMed] [Google Scholar]
- 4.Vinodhkumaradithyaa A, Uma A, Shirivasan M, Ananthalakshmi I, Nallasivam P, Thirumalaikolundusubramanian P. Nasal carriage of methicillin-resistant Staphylococcus aureus among surgical unit staff. Jpn J Infect Dis. 2009;62:228–229. [PubMed] [Google Scholar]
- 5.Gold OG, Jordan HV, Van Houte J. A selective medium for Streptococcus mutans. Arch Oral Biol. 1973;18:357–364. doi: 10.1016/0003-9969(73)90109-x. [DOI] [PubMed] [Google Scholar]
- 6.Tsuda H, Yamashita Y, Shibata Y, Nakano Y, Koga T. Genes involved in bacitracin resistance in Streptococcus mutans. Antimicrob Agents Chemother. 2002;46:3756–3764. doi: 10.1128/AAC.46.12.3756-3764.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Tsukioka Y, Yamashita Y, Nakano Y, Oho T, Koga T. Identification of a fourth gene involved in dTDP-rhamnose synthesis in Streptococcus mutans. J Bacteriol. 1997;179:4411–4414. doi: 10.1128/jb.179.13.4411-4414.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tsukioka Y, Yamashita Y, Oho T, Nakano Y, Koga T. Biological function of the dTDP-rhamnose synthesis pathway in Streptococcus mutans. J Bacteriol. 1997;179:1126–1134. doi: 10.1128/jb.179.4.1126-1134.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Shibata Y, Yamashita Y, Ozaki K, Nakano Y, Koga T. Expression and characterization of streptococcal rgp genes required for rhamnan synthesis in Escherichia coli. Infect Immun. 2002;70:2891–2898. doi: 10.1128/IAI.70.6.2891-2898.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lau PC, Sung CK, Lee JH, Morrison DA, Cvitkovitch DG. PCR ligation mutagenesis in transformable streptococci: application and efficiency. J Microbiol Methods. 2002;49:193–205. doi: 10.1016/s0167-7012(01)00369-4. [DOI] [PubMed] [Google Scholar]
- 11.Kitagawa N, Shiota S, Shibata Y, Takeshita T, Yamashita Y. Characterization of MbrC involved in bacitracin resistance in Streptococcus mutans. FEMS Microbiol Lett. 2011;318:61–67. doi: 10.1111/j.1574-6968.2011.02238.x. [DOI] [PubMed] [Google Scholar]
- 12.Chang C, Stewart CR. The two-component system1 regulation of diverse signaling pathways in prokaryotes and eukaryotes. Plant Physiol. 1998;117:723–731. doi: 10.1104/pp.117.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
