Quaternary ammonium-induced multidrug tolerant Streptococcus mutans persisters elevate cariogenic virulence in vitro

Abstract

Investigation of bacterial cells that can evade treatment for tooth decay has suggested a novel approach that could improve treatment. Streptococcus mutans, the main bacteria involved in tooth decay, are targeted with antibiotics called quaternary ammoniums, but some bacterial cells, known as persisters, can evade these drugs by becoming dormant, reducing the effectiveness of treatment. Lei Cheng from Suchuan University, China, and colleagues have now investigated the development of persisters when the usually highly effective quaternary ammonium dimethylaminododecyl methacrylate was used against cultures of S. mutans. Persisters were present after treatment, and exhibited tolerance to six other antibiotics. However, increasing the amount of glucose in the cultures to stimulate metabolism in the persisters reduced their numbers, suggesting that such a novel approach may improve antibacterial treatment for tooth decay.

Keywords

antibacterial quaternary ammoniums / dental caries / persistence / multidrug tolerance / Streptococcus mutans biofilms

References

[1] Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet, 2007, 369(9555): 51-59.

[2] Kuramitsu HK, He X, Lux R. Interspecies interactions within oral microbial communities. Microbiol Mol Biol Rev, 2008, 71(4): 653-670.

[3] Xu J, Li Y, Cao X. The effect of eugenol on the cariogenic properties of Streptococcus mutans and dental caries development in rats. Exp Ther Med, 2013, 5(6): 1667-1670.

[4] Yamashita Y, Bowen WH, Burne RA. Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. Infect Immun, 1993, 61(9): 3811-3817.

[5] Ge Y, Wang S, Zhou X. The use of quaternary ammonium to combat dental caries. Materials(Basel), 2015, 8(6): 3532-3549.

[6] Eckert R, Sullivan R, Shi W. Targeted antimicrobial treatment to re-establish a healthy microbial flora for long-term protection. Adv Dent Res, 2012, 24(2): 94-97.

[7] Zaltsman N, Keslershvero D, Weiss EI. Synthesis variants of quaternary ammonium polyethyleneimine nanoparticles and their antibacterial efficacy in dental materials. J Appl Biomater Funct Mater, 2016, 14(2): e205-e211.

[8] Zubris DL, Minbiole KP, Wuest WM. Polymeric quaternary ammonium compounds: versatile antimicrobial materials. Curr Top Med Chem, 2017, 17(3): 305-318.

[9] Beyth N, Yudovinfarber I, Bahir R. Antibacterial activity of dental composites containing quaternary ammonium polyethylenimine nanoparticles against Streptococcus mutans. Biomaterials, 2006, 27(21): 3995-4002.

[10] Mei L, Ren Y, Loontjens TJ. Contact-killing of adhering streptococci by a quaternary ammonium compound incorporated in an acrylic resin. Int J Artif Organs, 2012, 35(10): 854-863.

[11] He J, Söderling E, Vallittu PK. Investigation of double bond conversion, mechanical properties, and antibacterial activity of dental resins with different alkyl chain length quaternary ammonium methacrylate monomers (QAM). J Biomater Sci Polym Ed, 2013, 24(5): 565-573.

[12] Li F, Weir MD, Xu HH. Effects of quaternary ammonium chain length on antibacterial bonding agents. J Dent Res, 2013, 92(10): 932-938.

[13] Cheng L, Weir MD, Zhang K. Dental primer and adhesive containing a new antibacterial quaternary ammonium monomer dimethylaminododecyl methacrylate. J Dent, 2013, 41(4): 345-355.

[14] Wang S, Zhang K, Zhou X. Antibacterial effect of dental adhesive containing dimethylaminododecyl methacrylate on the development of Streptococcus mutans biofilm. Int J Mol Sci, 2014, 15(7): 12791-12806.

[15] Zhang K, Wang S, Zhou X. Effect of antibacterial dental adhesive on multispecies biofilms formation. J Dent Res, 2015, 94(4): 622-629.

[16] Wang S, Ge Y, Zhou X. Effect of anti-biofilm glass-ionomer cement on Streptococcus mutans biofilms. Int J Oral Sci, 2016, 8(2): 76-83.

[17] Hede K. Antibiotic resistance: An infectious arms race. Nature, 2014, 509(7498): S2-S3.

[18] Yoneyama H, Katsumata R. Antibiotic resistance in bacteria and its future for novel antibiotic development. Biosci Biotechnol Biochem, 2006, 70(5): 1060-1075.

[19] O'Brien TF, Stelling J. Integrated multilevel surveillance of the world's infecting microbes and their resistance to antimicrobial agents. Clin Microbiol Rev, 2011, 24(2): 281-295.

[20] Dominey-Howes D, Bajorek B, Michael CA. Applying the emergency risk management process to tackle the crisis of antibiotic resistance. Front Microbiol, 2015, 6: 927.

[21] Kitagawa H, Izutani N, Kitagawa R. Evolution of resistance to cationic biocides in Streptococcus mutans and Enterococcus faecalis. J Dent, 2016, 47: 18-22.

[22] Wang S, Wang H, Ren B. Do quaternary ammonium monomers induce drug resistance in cariogenic, endodontic and periodontal bacterial species?. Dent Mater, 2017, 33: 1127-1138.

[23] Gefen O, Balaban NQ. The importance of being persistent: heterogeneity of bacterial populations under antibiotic stress. FEMS Microbiol Rev, 2009, 33(4): 704-717.

[24] Lewis K. Persister cells. Annu Rev. Microbiol, 2010, 64(64): 357-372.

[25] Bigger JW. The bactericidal action of penicillin on Staphylococcus pyogenes. Ir J Med Sci, 1944, 19(12): 585-595.

[26] Jayaraman R. Bacterial persistence: some new insights into an old phenomenon. J Biosci, 2008, 33(5): 795-805.

[27] Levin BR, Rozen DE. Non-inherited antibiotic resistance. Nat Rev Microbiol, 2006, 4(7): 556-562.

[28] Fauvart M, De Groote VN, Michiels J. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol, 2011, 60(6): 699-709.

[29] Lafleur MD, Qi Q, Lewis K. Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother, 2010, 54(1): 39-44.

[30] Mulcahy LR, Burns JL, Lory S. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol, 2010, 192(23): 6191-6199.

[31] Levin-reisman I, Ronin I, Gefen O. Antibiotic tolerance facilitates the evolution of resistance. Science, 2017, 355(6327): 826-830.

[32] Lewis K, Shan Y. Why tolerance invites resistance. Science, 2017, 355(6327): 796.

[33] Page R, Peti W. Toxin-antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol, 2016, 12(4): 208-214.

[34] Wen Y, Behiels E, Devreese B. Toxin-Antitoxin systems: their role in persistence, biofilm formation, and pathogenicity. Pathog Dis, 2014, 70(3): 240-249.

[35] Leung V, Ajdic D, Koyanagi S. The formation of Streptococcus mutans persisters induced by the quorum-sensing peptide pheromone is affected by the LexA regulator. J Bacteriol, 2015, 197(6): 1083-1094.

[36] Haraszthy VI, Reynolds HS, Sreenivasan PK. Media- and method-dependent variations in minimal inhibitory concentrations of antiplaque agents on oral bacteria. Lett Appl Microbiol, 2006, 43(3): 256-261.

[37] Zheng X, Zhang K, Zhou X. Involvement of gshAB in the interspecies competition within oral biofilm. J Dent Res, 2013, 92(9): 819-824.

[38] Klein MI, Duarte S, Xiao J. Structural and molecular basis of the role of starch and sucrose in Streptococcus mutans biofilm development. Appl Environ Microbiol, 2009, 75(3): 837-841.

[39] Li M, Huang R, Zhou X. Effect of nicotine on dual-species biofilms of Streptococcus mutans and Streptococcus sanguinis. FEMS Microbiol Lett, 2014, 350(2): 125-132.

[40] Zhang K, Ren B, Zhou X. Effect of antimicrobial denture base resin on multi-species biofilm formation. Int J Mol Sci, 2016, 17(7): 1033.

[41] Orman MA, Brynildsen MP. Establishment of a method to rapidly assay bacterial persister metabolism. Antimicrob Agents Chemother, 2013, 57(9): 4398-4409.

[42] Cohen NR, Lobritz MA, Collins JJ. Microbial persistence and the road to drug resistance. Cell Host Microbe, 2013, 13(6): 632-642.

[43] Conlon BP. Staphylococcus aureus chronic and relapsing infections: evidence of a role for persister cells: an investigation of persister cells, their formation and their role in S. aureus disease. Bioessays, 2014, 36(10): 991-996.

[44] Keren I, Kaldalu N, Spoering A. Persister cells and tolerance to antimicrobials. Fems Microbiol Lett, 2004, 230(1): 13-18.

[45] Lechner S, Lewis K, Bertram R. Staphylococcus aureus persisters tolerant to bactericidal antibiotics. J Mol Microbiol Biotechnol, 2012, 22(4): 235-244.

[46] Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol, 2010, 8(6): 423-435.

[47] Lambert PA. Bacterial resistance to antibiotics: modified target sites. Adv Drug Deliv Rev, 2005, 57(57): 1471-1485.

[48] Pu Y, Ke Y, Bai F. Active efflux in dormant bacterial cells-new insights into antibiotic persistence. Drug Resist Updat, 2017, 30: 7-14.

[49] Pu Y, Zhao Z, Li Y. Enhanced efflux activity facilitates drug tolerance in dormant bacterial cells. Mol Cell, 2016, 62(2): 284-294.

[50] Butler MS, Hansford KA, Blaskovich MA. Glycopeptide antibiotics: back to the future. J Antibiot, 2014, 67(9): 631-644.

[51] Pertel PE, Eisenstein BI, Link AS. The efficacy and safety of daptomycin vs. vancomycin for the treatment of cellulitis and erysipelas. Int J Clin Pract, 2009, 63(3): 368-375.

[52] Beikler T, Flemmig TF. Oral biofilm-associated diseases: trends and implications for quality of life, systemic health and expenditures. Periodontol, 2011, 55(1): 87-103.

[53] Gün I, EkiNci FY. Biofilms: microbial life on surfaces. Emerg Infect Dis, 2009, 8(9): 881-890.

[54] Mihai MM, Holban AM, Giurcaneanu C. Microbial biofilms: impact on the pathogenesis of periodontitis, cystic fibrosis, chronic wounds and medical device-related infections. Curr Top Med Chem, 2015, 15(16): 1552-1576.

[55] Flemming HC, Neu TR, Wozniak DJ. The EPS matrix: the "house of biofilm cells". J Bacteriol, 2007, 189(22): 7945-7947.

[56] Xiao J, Klein MI, Falsetta ML. The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm. PLoS Pathog, 2012, 8(4): e1002623.

[57] Falsetta ML, Koo H. Beyond mucosal infection: a role for C. albicans-Streptococcal interactions in the pathogenesis of dental caries. Curr Oral Health Rep, 2014, 1(1): 86-93.

[58] Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature, 2011, 473(7346): 216-220.

[59] Amato SM, Orman MA, Brynildsen MP. Metabolic control of persister formation in Escherichia coli. Mol Cell, 2013, 50(4): 475-487.

[60] Allison KR, Brynildsen MP, Collins JJ. Heterogeneous bacterial persisters and engineering approaches to eliminate them. Curr Opin Microbiol, 2011, 14(5): 593-598.