MICROBIOLOGICAL REVIEWS, June 1980, p. 331-384 Vol. 44, No. 2 0146-0749/80/02-0331/54$02.00/0 Biology, Immunology, and Cariogenicity of Streptococcus mutanst SHIGEYUKI HAMADAt AND HUTTON D. SLADE* Department of Oral Biology, School ofDentistry, University of Colorado Health Sciences Center, Denver, Colorado 80262 INTRODUCTION 332 ORAL MICROBIAL FLORA 332 ISOLATION AND IDENTIFICATION OF S. MUTAINS AND OTHER ORAL STREPTOCOCCI ......... 333 Characteristic Properties of Oral Streptococci ... 333 S. mutans 333 S. sanguis 334 S. mitior 334 S. salivarius .............. 335 S. milleri ..... ... ............ 335 Selective Isolation of S. mutans ....... 335 CLASSIFICATION OF S. MUTANS 335 Immunological Typing of S. mutans 335 Serotype-Specific Antigens of S. mutans .... 336 Reactivity of S. mutans with Lectins .... ... 340 Cell Wall Structure of S. mutans and Other Streptococci .................... 340 POLYMER SYNTHESIS BY S. MUTANS 342 Extracellular Polysaccharides ............... ................. 342 Glucans .... ... 342 Fructans ....... 344 Polysaccharide-Synthesizing Enzymes ............................... 344 Intracellular Polysaccharides ............................... 345 Lipoteichoic Acid ............................... 345 Interaction of Glucosyltransferase with Various Agents , 346 Invertase 347 a(1-- 6) Glucanase .............................. 348 SUGAR METABOLISM BY S. MUTANS ....................................... 348 ADHERENCE OF S. MUTANS 348 Initial Attachment of S. mutans to Smooth Surfaces ........................ 348 Interaction of Salivary Components with Streptococcal Cells ............... 349 Implantation of S. mutans , 350 Sucrose-Dependent In Vivo Adherence of S. mutans ........................ 350 Sucrose-Dependent In Vitro Adherence of S. mutans ........................ 350 Cell-to-Cell Adherence: Bacterial Aggregation .............................. 352 GENETIC ASPECTS OF S. MUTANS 353 Lysogenicity and Plasmids .................................. 353 Transformation 354 BACTERIOCINS OF S. MUTANS: MUTACINS ......... ..........,., 354 Bacteriocinogeny Among S. mutans . .354 Extracellular Mutacins 355 IMMUNOLOGICAL ASPECTS OF S. MUTANS ....................... ... 356 Distribution of S. mutans Serotypes in Humans ,, 356 In Vitro Effects of Antisera Against S. mutans 356 Immunological Responses of Host to S. mutans . ............................ 356 Possible Vaccination with S. mutans Antigens .................... ... .... 357 CARIOGENICITY OF S. MUTANS IN EXPERIMENTAL ANIMALS ............ 358 Caries Induction in Animals ................................................ 358 Noncariogenic and Supercariogenic Mutants of S. mutans ,.. 359 S. MUTANS AND DENTAL CARIES IN HUMANS ........................... 360 Effect of Sucrose on the Proportion of S. mutans ............................ 360 Epidemiological Relationship Between S. mutans and Caries Development .. 360 t The survey of literature pertaining to this review was : Present address: Department of Oral Biology, Osaka Uni- terminated in October 1979. versity Dental School, Nakanoshima, Kita-ku, Osaka, 530 Japan. 331 332 HAMADA AND SLADE MICROBIOL. REV. PREVENTION OF CARIES CAUSED BY S. MUTANS ......................... 361 Suppression of S. mutans by Antimicrobial Agents .361 Inhibition of Adherence of S. mutans by Glucan-Hydrolyzing Enzyes .... 361 ENDOCARDMS CAUSED BY S. MUTANS ................. .............. 362 SUMMARY ............................ 363 LITERATlURE CmD ................................. ................. 364 INTRODUCTION current state of knowledge concerning S. mu- Whether there is any one bacterium which tans. Numerous reviews and books have re- may always be found in decayed dentine, and cently appeared on microbiological or immuno- which might therefore be entitled to the name logical aspects of dental caries, or oral strepto- of the bacterium of tooth decay, or whether cocci (27, 46, 196, 265, 303, 397, 438, 445, 494, there are various kinds which occur with consid- 549). erable constancy, we are not able to say. It is ORAL MICROBIAL FLORA now apparent, however, that various microor- ganisms are essential in the pathogenesis of den- The oral microflora is a complex ecosystem tal caries. Orland (451) first demonstrated that which contains a wide variety of microbial spe- selected streptococcal species, namely, entero- cies (Table 1). The mouth is colonized by various cocci, produced dental caries in germfree rats microorganisms before teeth erupt, although when fed a high-sucrose diet. Furthermore, in- newborn infants are essentially free from micro- direct evidence that antibiotics suppressed ex- organisms (394). With the eruption of teeth, perimental dental caries in rodents (396) dental plaque, distinctive patches primarily of strongly suggested the involvement of certain microbial origin, develop on exposed enamel sur- penicillin-susceptible bacteria in dental caries. faces which are covered by a pellicle that is an Since that time, various investigations have amorphous, almost invisible film composed pri- been carried out to elucidate the causative rela- marily of salivary glycoprotein (162, 194). Large tionship between specific oral bacterial species microbial masses develop on the teeth surfaces and dental caries. In 1960, some streptococcal unless proper oral hygiene measures are taken, strains, isolated from carious lesions of rats and hamsters, produced dental caries in "caries-re- TABLE 1. Distribution of bacteria on various sites sistant" rats and hamsters, respectively (157, in the human moutha 302). Site Using a sev- fluorescent-antibody technique, Bacterial group Gingi- eral streptococcal strains which shared immu- Plaque Tongue Saliva val nological specificity with the cariogenic strepto- crevice cocci derived from rats and hamsters were iso- Gram-positive facultative 28.2 44.8 46.2 28.8 lated from human carious lesions (275, 628, 629). cocci These strains also produced severe dental caries Streptococci 27.9 38.3 41.0 27.1 in germfree animals. Since then, similar strep- S. mutans (0-50) (0-1) (0-1) (0-30) S. sanguis (40-60) (10-20) (10-30) (10-20) tococcal species have been isolated from human S. mitior (20-40) (10-30) (30-50) (10-30) carious lesions by several investigators (183, 202, S. salivarius (0-1) (40-60) (40-60) (0-1) 321, 322). Carlsson (54, 55) indicated that prop- S. milleri (3-25) (0-1) (0-1) (14-56) erties of these cariogenic streptococci were sim- Staphylococci 0.3 6.5 4.0 1.7 Gram-positive anaerobic 12.6 4.2 13.0 7.4 ilar to those originally isolated from human car- cocci ious teeth by J. K. Clarke (81) in 1924 to which Gram-negative anaerobic 6.4 16.0 15.9 10.7 he had given the species name mutans. Thus, cocci the rediscovery of Streptococcus mutans fol- Gram-negative faculta- 0.4 3.4 1.2 I 0.4 tive cocci lowed the original observation by about 36 years. Gram-positive facultative 23.8 13.0 11.8 15.3 S. mutans is now considered to play an im- rods portant role in the development of dental caries Gram-positive anaerobic 18.4 8.2 4.8 20.2 in animals and humans. Extensive research on rods Gram-negative faculta- NDb 3.2 2.3 1.2 this microorganism has been done during the tive rods last 10 years. Unfortunately, however, S. mutans Gram-negative anaerobic 10.4 8.2 4.8 16.1 is not given an independent species position in rod the newest edition of Bergey's Manual ofDeter- Spirochetes ND ND ND 1.0 minative Bacteriology (43). It will be recognized Modified from Gibbons and van Houte (194, 196) and from the evidence described below that S. mu- Mejare and Edwardson (403). Data are expressed as a per- tans is the best-defined centage of total cultivable count on anaerobically incubated species among the oral blood agar. Data in parentheses are expressed as a percentage streptococci. of the total facultative streptococcal counts. The present review is an attempt to define the h ND, Not detected. VOL. 44, 1980 STREPTOCOCCUS MUTANS 333 whereas desquamation of epithelial cells does problems in obtaining representative samples not permit the heavy accumulation on oral mu- from different oral sites, and in dispersing, cul- cosal surfaces such as the dorsum of the tongue tivating, and enumerating the microorganisms. (195). The number of bacteria in dental plaque No single cultivation method of examining the can reach 108 per mg (wet weight) (192). complex and variable dental plaque flora will As shown in Table 1, predominant microbial satisfy all the necessary conditions. Strictly an- species are significantly different in different aerobic procedures will be required in many sites. Irrespective of variation from sample to cases. It is fortunate, however, that most oral sample, streptococci, gram-positive rods, and streptococcal species can be isolated from var- veillonellae comprise the majority of the total ious sites in the mouth by using a selective viable count. In plaque and gingival crevice, medium, mitis salivarius (MS) agar (Difco Lab- higher proportions of gram-positive and -nega- oratories, Detroit, Mich.). Although MS agar tive rods are observed. More recently, it has was originally devised by Chapman to isolate been demonstrated that samples obtained from fecal streptococci, the use of MS agar has dom- deep periodontal pockets in patients with ad- inated other cultural methods for the isolation vanced periodontitis and periodontosis consist of oral streptococci, including S. mutans, be- of a significantly higher percentage ofgram-neg- cause of its selective and differential properties. ative anaerobic rods (440, 536,