Characteristics of Streptococcus mutans strains lacking the MazEF and RelBE toxin–antitoxin modules
José A.C. Lemos
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorThomas A. Brown Jr.
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorJacqueline Abranches
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorCorresponding Author
Robert A. Burne
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
*Corresponding author. Tel.: +1 352 3924370/8462521; fax: +1 352 3927357., E-mail address: [email protected]Search for more papers by this authorJosé A.C. Lemos
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorThomas A. Brown Jr.
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorJacqueline Abranches
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
Search for more papers by this authorCorresponding Author
Robert A. Burne
Department of Oral Biology, University of Florida College of Dentistry, 1600 SW Archer Road, Gainesville, FL 32610-0424, United States
*Corresponding author. Tel.: +1 352 3924370/8462521; fax: +1 352 3927357., E-mail address: [email protected]Search for more papers by this authorEdited by T. Mitchell
Abstract
Two pairs of genes were identified in Streptococcus mutans with similarity to relBE and mazEF toxin–antitoxin (TA) modules of Escherichia coli. Transcription of mazEF and relBE was repressed by amino acid starvation, and relBE expression was repressed by low pH. Mutants lacking MazF, RelE, or both toxins (MRT1) grew in broth media and formed biofilms as well as the parent. Biofilm populations of MRT1 were more resistant to acid killing than the parent or single mutants. MRT1 also exhibited a longer diauxie during growth on glucose and inulin and displayed decreased phosphoenolpyruvate:sugar phosphotransferase activity. This is the first report that demonstrates a physiological role for TA modules in Gram-positive bacteria.
References
- [1] Lehnherr, H., Maguin, E., Jafri, S., Yarmolinsky, M.B. (1993) Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J. Mol. Biol. 233, 414–428.
- [2] Christensen, S.K., Gerdes, K. (2003) RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol. Microbiol. 48, 1389–1400.
- [3] Aizenman, E., Engelberg-Kulka, H., Glaser, G. (1996) An Escherichia coli chromosomal “addiction module” regulated by guanosine [corrected] 3′,5′-bispyrophosphate: a model for programmed bacterial cell death. Proc. Natl. Acad. Sci. USA 93, 6059–6063.
- [4] Christensen, S.K., Mikkelsen, M., Pedersen, K., Gerdes, K. (2001) RelE, a global inhibitor of translation, is activated during nutritional stress. Proc. Natl. Acad. Sci. USA 98, 14328–14333.
- [5] Pedersen, K., Christensen, S.K., Gerdes, K. (2002) Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol. Microbiol. 45, 501–510.
- [6] Zhang, Y., Zhang, J., Hoeflich, K.P., Ikura, M., Qing, G., Inouye, M. (2003) MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli. Mol. Cell. 12, 913–923.
- [7] Metzger, S., Dror, I.B., Aizenman, E., Schreiber, G., Toone, M., Friesen, J.D., Cashel, M., Glaser, G. (1988) The nucleotide sequence and characterization of the relA gene of Escherichia coli. J. Biol. Chem. 263, 15699–15704.
- [8] Hazan, R., Sat, B., Engelberg-Kulka, H. (2004) Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J. Bacteriol. 186, 3663–3669.
- [9] Sat, B., Hazan, R., Fisher, T., Khaner, H., Glaser, G., Engelberg-Kulka, H. (2001) Programmed cell death in Escherichia coli: some antibiotics can trigger mazEF lethality. J. Bacteriol. 183, 2041–2045.
- [10] Sat, B., Reches, M., Engelberg-Kulka, H. (2003) The Escherichia coli mazEF suicide module mediates thymineless death. J. Bacteriol. 185, 1803–1807.
- [11] Pedersen, K., Zavialov, A.V., Pavlov, M.Y., Elf, J., Gerdes, K., Ehrenberg, M. (2003) The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112, 131–140.
- [12] Gerdes, K. (2000) Toxin–antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J. Bacteriol. 182, 561–572.
- [13] Engelberg-Kulka, H., Sat, B., Reches, M., Amitai, S., Hazan, R. (2004) Bacterial programmed cell death systems as targets for antibiotics. Trends Microbiol. 12, 66–71.
- [14] Amitai, S., Yassin, Y., Engelberg-Kulka, H. (2004) MazF-mediated cell death in Escherichia coli: a point of no return. J. Bacteriol. 186, 8295–8300.
- [15] Pandey, D.P., Gerdes, K. (2005) Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucl. Acids Res. 33, 966–976.
- [16] Burne, R.A., Wen, Z.T., Chen, Y.Y., Penders, J.E. (1999) Regulation of expression of the fructan hydrolase gene of Streptococcus mutans GS-5 by induction and carbon catabolite repression. J. Bacteriol. 181, 2863–2871.
- [17] Terleckyj, B., Willett, N.P., Shockman, G.D. (1975) Growth of several cariogenic strains of oral streptococci in a chemically defined medium. Infect. Immun. 11, 649–655.
- [18] Lemos, J.A., Brown Jr., T.A., Burne, R.A. (2004) Effects of RelA on key virulence properties of planktonic and biofilm populations of Streptococcus mutans. Infect. Immun. 72, 1431–1440.
- [19] Loo, C.Y., Corliss, D.A., Ganeshkumar, N. (2000) Streptococcus gordonii biofilm formation: identification of genes that code for biofilm phenotypes. J. Bacteriol. 182, 1374–1382.
- [20] Burne, R.A., Schilling, K., Bowen, W.H., Yasbin, R.E. (1987) Expression, purification, and characterization of an exo-β-d-fructosidase of Streptococcus mutans. J. Bacteriol. 169, 4507–4517.
- [21] Sambrook, J., Fritsch, E.F., Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cols Spring Harbor, NY.
- [22] Ahn, S.J., Lemos, J.A., Burne, R.A. (2005) Role of HtrA in growth and competence of Streptococcus mutans UA159. J. Bacteriol. 187, 3028–3038.
- [23] LeBlanc, D.J., Crow, V.L., Lee, L.N., Garon, C.F. (1979) Influence of the lactose plasmid on the metabolism of galactose by Streptococcus lactis. J. Bacteriol. 137, 878–884.
- [24] Ajdic, D., McShan, W.M., McLaughlin, R.E., Savic, G., Chang, J., Carson, M.B., Primeaux, C., Tian, R., Kenton, S., Jia, H., Lin, S., Qian, Y., Li, S., Zhu, H., Najar, F., Lai, H., White, J., Roe, B.A., Ferretti, J.J. (2002) Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl. Acad. Sci. USA 99, 14434–14439.
- [25] Strauch, M.A., Perego, M., Burbulys, D., Hoch, J.A. (1989) The transition state transcription regulator AbrB of Bacillus subtilis is autoregulated during vegetative growth. Mol. Microbiol. 3, 1203–1209.
- [26] Tyndall, C., Meister, J., Bickle, T.A. (1994) The Escherichia coli prr region encodes a functional type IC DNA restriction system closely integrated with an anticodon nuclease gene. J. Mol. Biol. 237, 266–274.
- [27] Lemos, J.A., Abranches, J., Burne, R.A. (2005) Responses of cariogenic streptococci to environmental stresses. Curr. Issues Mol. Biol. 7, 95–107.
- [28] Yarmolinsky, M.B. (1995) Programmed cell death in bacterial populations. Science 267, 836–837.
- [29] Hayes, F. (2003) Toxins–antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301, 1496–1499.
- [30] Nystrom, T. (2003) Conditional senescence in bacteria: death of the immortals. Mol. Microbiol. 48, 17–23.
- [31] Rice, K.C., Bayles, K.W. (2003) Death's toolbox: examining the molecular components of bacterial programmed cell death. Mol. Microbiol. 50, 729–738.
- [32] Marquis, R.E. (1995) Oxygen metabolism, oxidative stress and acid–base physiology of dental plaque biofilms. J. Ind. Microbiol. 15, 198–207.
- [33] Dashper, S.G., Reynolds, E.C. (1992) pH regulation by Streptococcus mutans. J. Dent. Res. 71, 1159–1165.
- [34] Abranches, J., Chen, Y.Y., Burne, R.A. (2003) Characterization of Streptococcus mutans strains deficient in EIIAB Man of the sugar phosphotransferase system. Appl. Environ. Microbiol. 69, 4760–4769.
- [35] Wen, Z.T., Browngardt, C., Burne, R.A. (2001) Characterization of two operons that encode components of fructose-specific enzyme II of the sugar:phosphotransferase system of Streptococcus mutans. FEMS Microbiol. Lett. 205, 337–342.
