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Streptococcal bacteriocins and the case for Streptococcus salivarius as model oral probiotics

    Philip A Wescombe

    BLIS Technologies Ltd, Centre for Innovation, University of Otago, PO Box 56, Dunedin 9016, New Zealand.

    ,
    Nicholas CK Heng

    Department of Oral Sciences, Faculty of Dentistry, University of Otago, PO Box 647, Dunedin 9054, New Zealand.

    ,
    Jeremy P Burton

    BLIS Technologies Ltd, Centre for Innovation, University of Otago, PO Box 56, Dunedin 9016, New Zealand.

    ,
    Chris N Chilcott

    BLIS Technologies Ltd, Centre for Innovation, University of Otago, PO Box 56, Dunedin 9016, New Zealand.

    &
    John R Tagg

    † Author for correspondence

    Department of Microbiology & Immunology, University of Otago, PO Box 56, Dunedin 9016, New Zealand.

    Published Online:https://doi.org/10.2217/fmb.09.61

    Members of the Gram-positive bacterial genus Streptococcus are a diverse collection of species inhabiting many body sites and range from benign, nonpathogenic species to those causing life-threatening infections. The streptococci are also prolific producers of bacteriocins, which are ribosomally synthesized proteinaceous antibiotics that kill or inhibit species closely related to the producer bacterium. With the emergence of bacterial resistance to conventional antibiotics, there is an impetus to discover, and implement, new and preferably ‘natural’ antibiotics to treat or prevent bacterial infections, a niche that bacterial interference therapy mediated by bacteriocins could easily fill. This review focuses on describing the diversity of bacteriocins produced by streptococci and also puts forth a case for Streptococcus salivarius, a nonpathogenic and numerically predominant oral species, as an ideal candidate for development as the model probiotic for the oral cavity. S. salivarius is a safe species that not only produces broad-spectrum bacteriocins but harbors bacteriocin-encoding (and bacteriocin-inducing) transmissible DNA entities (megaplasmids).

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    Bibliography

    • Facklam R: What happened to the streptococci: overview of taxonomic and nomenclature changes. Clin. Microbiol. Rev.15,613–630 (2002).
    • Pasteur L, Joubert JF: Charbon et septicémie. C. R. Soc. Biol. Paris85,101–115 (1877).
    • Tagg JR, Bannister LV: “Fingerprinting” β-haemolytic streptococci by their production of and sensitivity to bacteriocine-like inhibitors. J. Med. Microbiol.12,397–411 (1979).▪▪ Original description of the deferred antagonism method, which has subsequently been used as the reference for the production (P)-typing of streptococcal bacteriocin-producing strains and is a useful first screen for novel bacteriocin producers.
    • Tagg JR: Streptococcal bacteriocin-like inhibitory substances: some personal insights into the bacteriocin-like activities produced by streptococci good and bad. Probiotics Antimicro. Prot.1,60–66 (2009).
    • Qi F, Chen P, Caufield PW: The group I strain of Streptococcus mutans, UA140, produces both the lantibiotic mutacin I and a nonlantibiotic bacteriocin, mutacin IV. Appl. Environ. Microbiol.67,15–21 (2001).
    • Wirawan RE, Swanson KM, Kleffmann T, Jack RW, Tagg JR: Uberolysin: a novel cyclic bacteriocin produced by Streptococcus uberis. Microbiology153,1619–1630 (2007).▪ First report of a cyclic bacteriocin produced by a streptococcal species.
    • Tagg JR, Dajani AS, Wannamaker LW: Bacteriocins of Gram-positive bacteria. Bacteriol. Rev.40,722–756 (1976).▪▪ Predicts the huge surge in interest in bacteriocins from Gram-positive bacteria and gives a useful overview of the characteristics of these bacteriocins.
    • Jack RW, Tagg JR, Ray B: Bacteriocins of Gram-positive bacteria. Microbiol. Rev.59,171–200 (1995).▪ Describes advances in bacteriocin biology in the decades since the Tagg et al. review [7].
    • Heng NCK, Wescombe PA, Burton JP, Jack RW, Tagg JR: The diversity of bacteriocins produced by Gram-positive bacteria. In: Bacteriocins – Ecology and Evolution. Riley MA, Chavan MA (Eds). Springer-Verlag, Berlin, Germany, 45–92 (2007).▪ Most recent review of the diversity of bacteriocins produced by Gram-positive bacteria. The division of all bacteriocins into the four distinct classes (outlined in this review) was first proposed here.
    • 10  Wescombe PA, Heng NCK, Jack RW, Tagg JR: Bacteriocins associated with cytotoxicity for eukaryotic cells. In: Microbial Toxins Molecular and Cellular Biology. 399–448 (2005).
    • 11  Jung G: Lantibiotics: a survey. In: Nisin and Novel Lantibiotics. Jung G, Sahl H-G (Eds). Escom Publishers, Leiden, The Netherlands, 1–34 (1991).
    • 12  McAuliffe O, Ross RP, Hill C: Lantibiotics: structure, biosynthesis and mode of action. FEMS Microbiol. Rev.25,285–308 (2001).
    • 13  Chatterjee C, Paul M, Xie L, van der Donk WA: Biosynthesis and mode of action of lantibiotics. Chem. Rev.105,633–684 (2005).▪ Extremely comprehensive review of lantibiotics that covers nearly every aspect of these interesting and relevant molecules. Especially useful for researchers who want in-depth knowledge about the different groups of lantibiotics and their relatedness.
    • 14  Wescombe PA, Upton M, Dierksen KP et al.: Production of the lantibiotic salivaricin A and its variants by oral streptococci and use of a specific induction assay to detect their presence in human saliva. Appl. Environ. Microbiol.72,1459–1466 (2006).
    • 15  Simpson WJ, Ragland NL, Ronson CW, Tagg JR: A lantibiotic gene family widely distributed in Streptococcus salivarius and Streptococcus pyogenes. Dev. Biol. Stand.85,639–643 (1995).
    • 16  Phelps HA, Neely MN: SalY of the Streptococcus pyogenes lantibiotic locus is required for full virulence and intracellular survival in macrophages. Infect. Immun.75,4541–4551 (2007).▪▪ First description of a second function of a gene product from a lantibiotic locus. This paper describes the importance of the salivaricin A immunity protein for intracellular survival of Streptococcus pyogenes in phagocytes.
    • 17  Kizy AE, Neely MN: First Streptococcus pyogenes signature-tagged mutagenesis screen identifies novel virulence determinants. Infect. Immun.77,1854–1865 (2009).
    • 18  Tagg JR, Pybus V, Phillips LV, Fiddes TM: Application of inhibitor typing in a study of the transmission and retention in the human mouth of the bacterium Streptococcus salivarius. Arch. Oral Biol.28,911–915 (1983).
    • 19  Upton M, Tagg JR, Wescombe P, Jenkinson HF: Intra- and interspecies signaling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides. J. Bacteriol.183,3931–3938 (2001).
    • 20  Dierksen KP, Moore CJ, Inglis M, Wescombe PA, Tagg JR: The effect of ingestion of milk supplemented with salivaricin A-producing Streptococcus salivarius on the bacteriocin-like inhibitory activity of streptococcal populations on the tongue. FEMS Microbiol. Ecol.59,584–591 (2007).
    • 21  Hyink O, Wescombe PA, Upton M, Ragland N, Burton JP, Tagg JR: Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12. Appl. Environ. Microbiol.73,1107–1113 (2007).
    • 22  Wescombe PA, Burton JP, Cadieux PA et al.: Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius. Antonie Van Leeuwenhoek90,269–280 (2006).▪▪ First report of the existence of megaplasmids in streptococci.
    • 23  Wescombe PA: Characterisation of lantibiotics produced by Streptococcus salivarius and Streptococcus pyogenes. PhD thesis, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand (2002).
    • 24  Georgalaki MD, Van Den Berghe E, Kritikos D et al.: Macedocin, a food-grade lantibiotic produced by Streptococcus macedonicus ACA-DC 198. Appl. Environ. Microbiol.68,5891–5903 (2002).
    • 25  Hynes WL, Friend VL, Ferretti JJ: Duplication of the lantibiotic structural gene in M-type 49 group A streptococcus strains producing streptococcin A-M49. Appl. Environ. Microbiol.60,4207–4209 (1994).
    • 26  Papadelli M, Karsioti A, Anastasiou R, Georgalaki M, Tsakalidou E: Characterization of the gene cluster involved in the biosynthesis of macedocin, the lantibiotic produced by Streptococcus macedonicus. FEMS Microbiol. Lett.272,75–82 (2007).
    • 27  Karaya K, Shimizu T, Taketo A: New gene cluster for lantibiotic streptin possibly involved in streptolysin S formation. J. Biochem. (Tokyo)129,769–775 (2001).
    • 28  Wescombe PA, Tagg JR: Purification and characterization of streptin, a type A1 lantibiotic produced by Streptococcus pyogenes. Appl. Environ. Microbiol.69,2737–2747 (2003).
    • 29  Hynes WL, Tagg JR: Bacteriocin-like activity of an M-type 25 group A streptococus. Proc. Univ. Otago Med. Sch.62,109–110 (1984).
    • 30  Hynes WL, Tagg JR: Production of broad-spectrum bacteriocin-like activity by group A streptococci of particular M-types. Zentralbl. Bakteriol. Mikrobiol. Hyg. A259,155–164 (1985).
    • 31  Heng NC, Burtenshaw GA, Jack RW, Tagg JR: Ubericin A, a class IIa bacteriocin produced by Streptococcus uberis. Appl. Environ. Microbiol.73,7763–7766 (2007).
    • 32  Hale JD, Heng NC, Jack RW, Tagg JR: Identification of nlmTE, the locus encoding the ABC transport system required for export of nonlantibiotic mutacins in Streptococcus mutans. J. Bacteriol.187,5036–5039 (2005).
    • 33  Heng NC, Tagg JR, Tompkins GR: Competence-dependent bacteriocin production by Streptococcus gordonii DL1 (Challis). J. Bacteriol.189,1468–1472 (2007).
    • 34  Kreth J, Merritt J, Shi W, Qi F: Co-ordinated bacteriocin production and competence development: a possible mechanism for taking up DNA from neighbouring species. Mol. Microbiol.57,392–404 (2005).
    • 35  Kreth J, Merritt J, Shi W, Qi F: Competition and coexistence between Streptococcus mutans and Streptococcus sanguinis in the dental biofilm. J. Bacteriol.187,7193–7203 (2005).
    • 36  Heng NC, Tagg JR, Tompkins GR: Identification and characterization of the loci encoding the competence-associated alternative σ factor of Streptococcus gordonii. FEMS Microbiol. Lett.259,27–34 (2006).
    • 37  Hale JD, Ting YT, Jack RW, Tagg JR, Heng NC: Bacteriocin (mutacin) production by Streptococcus mutans genome sequence reference strain UA159: elucidation of the antimicrobial repertoire by genetic dissection. Appl. Environ. Microbiol.71,7613–7617 (2005).
    • 38  Perry JA, Jones MB, Peterson SN, Cvitkovitch DG, Levesque CM: Peptide alarmone signalling triggers an auto-active bacteriocin necessary for genetic competence. Mol. Microbiol.72(4),905–917 (2009).
    • 39  Akesson M, Dufour M, Sloan GL, Simmonds RS: Targeting of streptococci by zoocin A. FEMS Microbiol. Lett.270,155–161 (2007).
    • 40  Heng NC, Ragland NL, Swe PM et al.: Dysgalacticin: a novel, plasmid-encoded antimicrobial protein (bacteriocin) produced by Streptococcus dysgalactiae subsp. equisimilis. Microbiology152,1991–2001 (2006).
    • 41  Heng NC, Burtenshaw GA, Jack RW, Tagg JR: Sequence analysis of pDN571, a plasmid encoding novel bacteriocin production in M-type 57 Streptococcus pyogenes. Plasmid52,225–229 (2004).
    • 42  Beukes M, Hastings JW: Self-protection against cell wall hydrolysis in Streptococcus milleri NMSCC 061 and analysis of the millericin B operon. Appl. Environ. Microbiol.67,3888–3896 (2001).
    • 43  Simmonds RS, Naidoo J, Jones CL, Tagg JR: The streptococcal bacteriocin-like inhibitory substance, zoocin A, reduces the proportion of Streptococcus mutans in an artificial plaque. Microb. Ecol. Health Dis.8,281–292 (1995).
    • 44  Heng NCK, Swe PM, Ting YT et al.: The large antimicrobial proteins (bacteriocins) of streptococci. Int. Congr. Ser.1289,351–354 (2006).
    • 45  Swe PM, Cook GM, Tagg JR, Jack RW: Mode of action of dysgalacticin: a large heat-labile bacteriocin. J. Antimicrob. Chemother.63,679–686 (2009).
    • 46  Maqueda M, Galvez A, Bueno MM et al.: Peptide AS-48: prototype of a new class of cyclic bacteriocins. Curr. Protein Pept. Sci.5,399–416 (2004).
    • 47  Oe Y, Soejima H, Nakayama H et al.: Significant association between score of periodontal disease and coronary artery disease. Heart Vessels24,103–107 (2009).
    • 48  Hillman JD, Mo J, McDonell E, Cvitkovitch D, Hillman CH: Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials. J. Appl. Microbiol.102,1209–1219 (2007).▪▪ Describes proposed use of a genetically modified member of the oral microbiota as a probiotic.
    • 49  Smith L, Hillman J: Therapeutic potential of type A (I) lantibiotics, a group of cationic peptide antibiotics. Curr. Opin. Microbiol.11,401–408 (2008).
    • 50  Smith L, Hasper H, Breukink E et al.: Elucidation of the antimicrobial mechanism of mutacin 1140. Biochemistry47,3308–3314 (2008).
    • 51  Ghobrial OG, Derendorf H, Hillman JD: Development and validation of a LC-MS quantification method for the lantibiotic MU1140 in rat plasma. J. Pharm. Biomed. Anal.49,970–975 (2009).
    • 52  Ghobrial OG, Derendorf H, Hillman JD: Pharmacodynamic activity of the lantibiotic MU1140. Int. J. Antimicrob. Agents33,70–74 (2009).
    • 53  Sanders E: Bacterial Interference. I. Its occurrence among the respiratory tract flora and characterisation of inhibition of group A streptococci by viridans streptococci. J. Infect. Dis.120,698–707 (1969).▪▪ Early important observation of potential interference with group A streptococcal establishment by commensal streptococci.
    • 54  Crowe CC, Sanders WE, Longley S: Bacterial interference. II. Role of the normal throat flora in prevention of colonization by group A Streptococcus. J. Infect. Dis.128,527–532 (1973).
    • 55  Bochkov IA: Nasopharyngeal microorganisms – antagonists of meningococci. Zh. Mikrobiol. Epidemiol. Immunobiol.81–86 (1975).
    • 56  Sanders CC, Sanders WE, Harrowe DJ: Bacterial interference: effects of oral antibiotics on the normal throat flora and its ability to interfere with group A streptococci. Infect. Immun.13,808–812 (1976).
    • 57  Bill NJ, Washington JA: Bacterial interference by Streptococcus salivarius. Am. J. Clin. Pathol.64,116–120 (1975).
    • 58  Grahn E, Holm SE: Bacterial interference in the throat flora during a streptococcal tonsillitis outbreak in an apartment house area. Zentralbl. Bakteriol. Mikrobiol. Hyg. A256,72–79 (1983).
    • 59  Fujimori I, Nozawa I, Kikushima K, Goto R, Hisamatatsu K, Murakami Y: Interaction between oral α-streptococci and group A streptococci in patients with tonsillitis. Ann. Otol. Rhinol. Laryngol.106,571–574 (1997).
    • 60  Fujimori I, Yamada T: Incidence of α-streptococcus having inhibitory activity against β-streptococcus in patients with tonsillitis. Nippon Jibiinkoka Gakkai Kaiho95,400–408 (1992).
    • 61  Yamada T, Yokota Y, Ikeda F, Mine Y, Kitada T: Antibacterial activity of cefixime against Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae in the presence of Moraxella (Branhamella) catarrhalis. Chemotherapy38,28–35 (1992).
    • 62  Brook I, Gober AE: Bacterial interference in the nasopharynx and nasal cavity of sinusitis prone and non-sinusitis prone children. Acta Otolaryngol.119,832–836 (1999).
    • 63  Roos K, Grahn E, Holm SE, Johansson H, Lind L: Interfering α-streptococci as a protection against recurrent streptococcal tonsillitis in children. Int. J. Pediatr. Otorhinolaryngol.25,141–148 (1993).
    • 64  Roos K, Hakansson EG, Holm S: Effect of recolonisation with “interfering” α streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ322,210–212 (2001).
    • 65  Roos K, Holm SE, Grahn E, Lind L: α-streptococci as supplementary treatment of recurrent streptococcal tonsillitis: a randomized placebo-controlled study. Scand. J. Infect. Dis.25,31–35 (1993).
    • 66  Falck G, Grahn-Hakansson E, Holm SE, Roos K, Lagergren L: Tolerance and efficacy of interfering α-streptococci in recurrence of streptococcal pharyngotonsillitis: a placebo-controlled study. Acta Otolaryngol.119,944–948 (1999).
    • 67  Dierksen KP, Inglis M, Tagg JR: High pharyngeal carriage rates of Streptococcus pyogenes in Dunedin school children with a low incidence of rheumatic fever. NZ Med. J.113,496–499 (2000).
    • 68  Fantinato V, Jorge AOC, Shimizu MT: Production of bacteriocin-like inhibitory substances (BLIS) by Streptococcus salivarius strains isolated from the tongue and throat of children with and without sore throat. Revista de Microbiologia30,332–334 (1999).
    • 69  Tano K, Grahn-Hakansson E, Holm SE, Hellstrom S: Inhibition of OM pathogens by α-hemolytic streptococci from healthy children, children with SOM and children with rAOM. Int. J. Pediatr. Otorhinolaryngol.56,185–190 (2000).
    • 70  Walls T, Power D, Tagg J: Bacteriocin-like inhibitory substance (BLIS) production by the normal flora of the nasopharynx: potential to protect against otitis media? J. Med. Microbiol.52,829–833 (2003).
    • 71  Tanzer JM, Kurasz AB, Clive J: Inhibition of ecological emergence of mutans streptococci naturally transmitted between rats and consequent caries inhibition by Streptococcus salivarius TOVE-R infection. Infect. Immun.49,76–83 (1985).
    • 72  Tanzer JM, Kurasz AB, Clive J: Competitive displacement of mutans streptococci and inhibition of tooth decay by Streptococcus salivarius TOVE-R. Infect. Immun.48,44–50 (1985).▪ Describes targeted interference of mutans streptococci by the introduction of Streptococcus salivarius. Note that this study was carried out in a rat model.
    • 73  Tanzer JM, Kurasz AB, Clive J: Inhibiton of ecological emergence of mutans streptococci naturally transmitted between rats and consequent caries inhibition by Streptococcus salivarius TOVE-R infection. Infect. Immun.49,76–83 (1985).
    • 74  Kurasz AB, Tanzer JM, Bazer L, Savoldi E: In vitro studies of growth and competition between S. salivarius TOVE-R and mutans streptococci. J. Dent. Res.65,1149–1153 (1986).
    • 75  Sliepen I, Hofkens J, Van Essche M, Quirynen M, Teughels W: Aggregatibacter actinomycetemcomitans adhesion inhibited in a flow cell. Oral Microbiol. Immunol.23,520–524 (2008).
    • 76  Van Hoogmoed CG, Geertsema-Doornbusch GI, Teughels W, Quirynen M, Busscher HJ, Van der Mei HC: Reduction of periodontal pathogens adhesion by antagonistic strains. Oral Microbiol. Immunol.23,43–48 (2008).
    • 77  Teughels W, Newman MG, Coucke W et al.: Guiding periodontal pocket recolonization: a proof of concept. J. Dent. Res.86,1078–1082 (2007).
    • 78  Kazor CE, Mitchell PM, Lee AM et al.: Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients. J. Clin. Microbiol.41,558–563 (2003).
    • 79  Burton J, Chilcott C, Tagg J: The rationale and potential for the reduction of oral malodour using Streptococcus salivarius probiotics. Oral Dis.11,29–31 (2005).
    • 80  Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR: A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J. Appl. Microbiol.100,754–764 (2006).▪▪ Demonstrates a direct effect of the application of S. salivarius K12 on oral malodor, which is the first description of a measurable outcome from the use of a streptococcal probiotic.
    • 81  Tong H, Chen W, Merritt J, Qi F, Shi W, Dong X: Streptococcus oligofermentans inhibits Streptococcus mutans through conversion of lactic acid into inhibitory H2O2: a possible counteroffensive strategy for interspecies competition. Mol. Microbiol.63,872–880 (2007).
    • 82  Balakrishnan M, Simmonds RS, Tagg JR: Diverse activity spectra of bacteriocin-like inhibitory substances having activity against mutans streptococci. Caries Res.35,75–80 (2001).
    • 83  van der Hoeven JS, Schaeken MJ: Streptococci and actinomyces inhibit regrowth of Streptococcus mutans on gnotobiotic rat molar teeth after chlorhexidine varnish treatment. Caries Res.29,159–162 (1995).
    • 84  van der Hoeven JS, van den Kieboom CW, Schaeken MJ: Sulfate-reducing bacteria in the periodontal pocket. Oral Microbiol. Immunol.10,288–290 (1995).
    • 85  Kang MS, Chung J, Kim SM, Yang KH, Oh JS: Effect of Weissella cibaria isolates on the formation of Streptococcus mutans biofilm. Caries Res.40,418–425 (2006).
    • 86  Kumar PS, Leys EJ, Bryk JM, Martinez FJ, Moeschberger ML, Griffen AL: Changes in periodontal health status are associated with bacterial community shifts as assessed by quantitative 16S cloning and sequencing. J. Clin. Microbiol.44,3665–3673 (2006).
    • 87  Favier CF, Vaughan EE, De Vos WM, Akkermans AD: Molecular monitoring of succession of bacterial communities in human neonates. Appl. Environ. Microbiol.68,219–226 (2002).
    • 88  Park HK, Shim SS, Kim SY et al.: Molecular analysis of colonized bacteria in a human newborn infant gut. J. Microbiol.43,345–353 (2005).
    • 89  Carlsson J, Grahnen H, Jonsson G, Wikner S: Early establishment of Streptococcus salivarius in the mouths of infants. J. Dent. Res.49,415–418 (1970).
    • 90  Frandsen EV, Pedrazzoli V, Kilian M: Ecology of viridans streptococci in the oral cavity and pharynx. Oral Microbiol. Immunol.6,129–133 (1991).
    • 91  Liljemark WF, Gibbons RJ: Suppression of Candida albicans by human oral streptococci in gnotobiotic mice. Infect. Immun.8,846–849 (1973).
    • 92  MacFarlane TW: The oral ecology of patients with severe Sjogren’s syndrome. Microbios41,99–106 (1984).
    • 93  Dierksen KP, Ragland NL, Tagg JR: A new alkaline pH-adjusted medium enhances detection of β-hemolytic streptococci by minimizing bacterial interference due to Streptococcus salivarius. J. Clin. Microbiol.38,643–650 (2000).
    • 94  Dierksen KP, Tagg JR: The influence of indigenous bacteriocin producing Streptococcus salivarius on the acquisition of Streptococcus pyogenes by primary school children in Dunedin, New Zealand. In: Streptococci and Streptococcal Diseases: Entering the New Millenium. Martin DR, Tagg JR (Eds). Securacopy, Wellington, New Zealand, 81–85 (2000).
    • 95  Heikkila MP, Saris PE: Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. J. Appl. Microbiol.95,471–478 (2003).
    • 96  Martin R, Langa S, Reviriego C et al.: The commensal microflora of human milk: new perspectives for food bacteriotherapy and probiotics. Trends Food Sci. Technol.15,121–127 (2004).
    • 97  Dalidowitz C: Fortified breast milk safety. J. Am. Diet. Assoc.105,1572–1573 (2005).
    • 98  Martin R, Heilig HG, Zoetendal EG et al.: Cultivation-independent assessment of the bacterial diversity of breast milk among healthy women. Res. Microbiol.158,31–37 (2007).
    • 99  Abdelgadir WS, Hamad SH, Møller PL, Jakobsen M: Characterisation of the dominant microbiota of Sudanese fermented milk Rob. Int. Dairy J.11,63–70 (2001).
    • 100  Mogensen G, Salminen S, O’Brien J et al.: Health benefits and safety evaluation of certain food components. Food microorganisms – health benefits, safety evaluation and strains with documented history of use in foods. Int. Dairy Fed. (IDF)4–20 (2002).
    • 101  Abdelgadir WS, Hamad SH, Møller PL, Jakobsen M: Diversity of lactic acid bacteria isolated from AOC Salers cheese. J. Dairy Res.71,231–244 (2004).
    • 102  Kurwijila L: Technologies for enhancing value addition, quality and safety of milk produced by smallholder farmers in Africa. Proceedings of the 4th All Africa Conference on Animal Agriculture (AACAA) and 31st Annual Meeting of Tanzania Society for Animal Production (TSAP). Arusha, Tanzania, 20–24 September 2005.
    • 103  Pesic-Mikulec D: Microbiological study of fresh white cheese. Appl. Ecol. Environ. Res.4,129–134 (2005).
    • 104  Obodai M, Dodd CE: Characterization of dominant microbiota of a Ghanaian fermented milk product, nyarmie, by culture- and nonculture-based methods. J. Appl. Microbiol.100,1355–1363 (2006).
    • 105  Van Hoorde K, Verstraete T, Vandamme P, Huys G: Diversity of lactic acid bacteria in two Flemish artisan raw milk Gouda-type cheeses. Food Microbiol.25,929–935 (2008).
    • 106  Jaine R, Baker M, Venugopal K: Epidemiology of acute rheumatic fever in New Zealand 1996–2005. J. Paediatr. Child Health44,564–571 (2008).
    • 107  North DA, Heynes RA, Lennon DR, Neutze J: Analysis of costs of acute rheumatic fever and rheumatic heart disease in Auckland. NZ Med. J.106,400–403 (1993).
    • 108  Burton JP, Wescombe PA, Tagg JR, Chilcott CN: Safety assessment of the oral cavity probiotic Streptococcus salivarius K12. Appl. Environ. Microbiol.72,3050–3053 (2006).
    • 109  Maragkoudakis PA, Papadelli M, Georgalaki M et al.: In vitro and in vivo safety evaluation of the bacteriocin producer Streptococcus macedonicus ACA-DC 198. Int. J. Food Microbiol.133,141–147 (2009).
    • 110  Qi F, Chen P, Caufield PW: Purification of mutacin III from group III Streptococcus mutans UA787 and genetic analyses of mutacin III biosynthesis genes. Appl. Environ. Microbiol.65,3880–3887 (1999).
    • 111  Wirawan RE, Klesse NA, Jack RW, Tagg JR: Molecular and genetic characterization of a novel nisin variant produced by Streptococcus uberis. Appl. Environ. Microbiol.72,1148–1156 (2006).
    • 112  Mantovani HC, Russell JB: Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, catalyzes the efflux of intracellular potassium but not ATP. Antimicrob. Agents Chemother.52,2247–2249 (2008).
    • 113  Mota-Meira M, Morency H, Lavoie MC: In vivo activity of mutacin B-Ny266. J. Antimicrob. Chemother.56,869–871 (2005).
    • 114  Hillman JD, Novak J, Sagura E et al.: Genetic and biochemical analysis of mutacin 1140, a lantibiotic from Streptococcus mutans. Infect. Immun.66,2743–2749 (1998).
    • 115  Qi F, Chen P, Caufield PW: Purification and biochemical characterization of mutacin I from the group I strain of Streptococcus mutans, CH43, and genetic analysis of mutacin I biosynthesis genes. Appl. Environ. Microbiol.66,3221–3229 (2000).
    • 116  Ross KF, Ronson CW, Tagg JR: Isolation and characterization of the lantibiotic salivaricin A and its structural gene salA from Streptococcus salivarius 20P3. Appl. Environ. Microbiol.59,2014–2021 (1993).▪ First characterization of a lantibiotic produced by S. salivarius.
    • 117  Jack RW, Tagg JR: Isolation and partial structure of streptococcin A-FF22. In: Nisin and Novel Lantibiotics. Jung G, Sahl H-G (Eds). Escom Publishers, Leiden, The Netherlands, 171–179 (1991).
    • 118  Robson CL, Wescombe PA, Klesse NA, Tagg JR: Isolation and partial characterization of the Streptococcus mutans type AII lantibiotic mutacin K8. Microbiology153,1631–1641 (2007).
    • 119  Chikindas ML, Novak J, Driessen AJ, Konings WN, Schilling KM, Caufield PW: Mutacin II, a bactericidal lantibiotic from Streptococcus mutans. Antimicrob. Agents Chemother.39,2656–2660 (1995).
    • 120  Xiao H, Chen X, Chen M, Tang S, Zhao X, Huan L: Bovicin HJ50, a novel lantibiotic produced by Streptococcus bovis HJ50. Microbiology150,103–108 (2004).
    • 121  Yonezawa H, Kuramitsu HK: Genetic analysis of a unique bacteriocin, Smb, produced by Streptococcus mutans GS5. Antimicrob. Agents Chemother.49,541–548 (2005).
    • 122  Hyink O, Balakrishnan M, Tagg JR: Streptococcus rattus strain BHT produces both a class I two-component lantibiotic and a class II bacteriocin. FEMS Microbiol. Lett.252(2),235–241 (2005).
    • 201  WHO/73 PR: Attacking the attacker: WHO steps up its fight against rheumatic fever. (1999). www.who.int/inf-pr-1999/en/pr99-73.html