Why is streptococcus important

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O'Toole, G. Biofilm formation as microbial development. Patenge, N. Wright stains made within the first 3 h after the fresh blood cultures showed striking intracapsular granules figure 2 , similar to those that had previously been reported by Seastone [ 10 ]. Reprinted with permission from [ 24 ]. The germ-free mice were as resistant as the conventional mice to challenge with GAS strains lacking both M protein and capsules [ 27 ] table 1.

Furthermore, the WBCs of newborn, colostrum-deprived piglets readily phagocytized M-negative, capsule-negative GAS strains and destroyed them with the same efficiency as the blood cells of normal, colostrum-fed piglets. Maximal virulence was demonstrated only in strains that were both M protein rich and heavily encapsulated [ 28 ]. During convalescence from pharyngitis, progressive loss of GAS strain virulence was clearly demonstrated by Rothbard and Watson [ 29 , 30 ].

Interestingly, during epidemics of rheumatic fever at Warren Air Force Base, the GAS found in the dust of recruits' barracks failed to infect human throats [ 31 ]. By the s, it became clear that the high attack rate of rheumatic fever noted in military epidemics did not apply to endemic GAS pharyngitis in schoolchildren [ 32 ].

GAS strains were often cultured from clinically mild pharyngitides, as well as in samples obtained from convalescent or asymptomatic carriers [ 33 ]. The virulence of GAS strains isolated from sporadic infections in schoolchildren from Chicago, Illinois, contrasted strikingly with that of the strains isolated from military epidemics [ 34 , 35 ].

For example, of 95 M-typeable strains isolated from mild, nonexudative sore throats of Chicago schoolchildren, only a single isolate formed mucoid colonies table 2. The others, although still M positive, produced only glossy pearly colonies figure 1B [ 34 ].

Most of these contained relatively small amounts of extractable M protein, expressed small or no visible capsule, were low in mouse virulence, and were weakly resistant to phagocytosis table 2 [ 34 ]. Limited virulence properties of group A Streptococcus GAS strains isolated from throat cultures of children with nonexudative pharyngitis who were not treated with antibiotics.

Further review of the existing literature [ 37 , 38 ] confirmed the limited M type association. In the reports available for review, the state of encapsulation was not described.

Indeed, with the continued dramatic decrease in the prevalence of rheumatic fever in developed countries in the s [ 39 ], description of GAS colonies on blood agar was rarely reported.

After the standardization of an emm -typing system based on the nucleotide sequence encoding the N-terminus of the mature M protein, GAS reference laboratories widely adopted this sensitive method of M typing [ 40 ], but identification of colony morphology as a marker of strain virulence was rarely noted. In the s, focal epidemics of rheumatic fever erupted in cohorts of children in several US states-notably Utah, Ohio, and Pennsylvania [ 41—44 ]—and in some US military installations [ 45 , 46 ] e.

The M types of the strains causing these outbreaks were eventually found to be the same as the notorious rheumatogenic strains of the earlier World War II military epidemics [ 47 ].

The state of encapsulation of these strains was not reported originally, and systematic studies of their virulence were not made [ 48 ]. Later, retrospective analysis of outbreaks of invasive GAS infection that followed revealed that mucoid colonies were often identified in some isolates from affected cohorts-notably, M types 3 and 18 [ 49 ].

Finally, a retrospective study of the colonial morphology of the GAS isolates recovered from patients with pharyngitis was made during several years of recurrent waves of acute rheumatic fever in the Salt Lake City, Utah, region [ 50 ]. Identification of the genome of some of these strains revealed that a single virulent clone may have been responsible for the epidemics of rheumatic fever reported from the Rocky Mountain States and elsewhere [ 51 , 52 ] and that a single genetically identified clone also caused an outbreak of invasive streptococcal disease among schoolchildren in Minnesota [ 53 ].

Correlation between the outbreaks of acute rheumatic fever and the prevalence of mucoid strains in the intermountain region of Utah during — Reprinted with permission from [ 50 ]. By the mids, the adherence of GAS to pharyngeal cells was shown to be due to several fibronectin-binding ligands, such as lipoteichoic acid [ 54 , 55 ] and the so-called F proteins [ 56 ], rather than to M protein alone. In contrast, the hyaluronate capsule apparently impeded GAS adherence to and internalization within Hep-2 cells and human keratinocytes [ 59—62 ].

The capsule's role in these studies was finally clarified by the demonstration that it attaches to a hyaluronic-acid-binding protein, CD44, which is present on human epithelial cells [ 63—66 ] and which induces cytoskeletal rearrangements, resulting in disruption of intercellular junctions, thus allowing the microorganisms to remain extracellular as they penetrate the epithelium [ 65 ].

More recently, strains of M types 3 and 18 that were strongly associated with the reappearance of rheumatic fever in the United States in the s were shown to avidly aggregate type IV collagen [ 67 ]. Such aggregation was found to depend on the expression of both M protein and hyaluronate and was demonstrated in vivo mouse skin as well as in vitro. The demonstration of the 2-component system regulating the operon that controls the hyaluronate producing genes has A, has B, and has C [ 68—72 ] has helped to explain the wide variation in encapsulation and the factors affecting its expression or repression.

The system consists of a membrane-integrated sensor protein CsrS , and a cytoplasmic response negative regulator CsrR also called CovRS. The gene sag A of the powerful toxin, streptolysin S, is also regulated by the same repressor [ 72 ].

The sensor protein CsrS responds to environmental signals. Contact with serum, for example, apparently derepresses synthesis of both hyaluronate and streptolysin S. The latter destroys cell membranes and vacuoles [ 73 ]. It is thus a natural partner of the capsule for invasiveness. Its role in virulence is usually underestimated [ 74 , 75 ]. A separate regulator Mga controls, among other genes, emm for M protein production [ 70 ]. Regulation by Mga is also responsive to environmental conditions, such as increased carbon dioxide concentrations [ 76 ].

Thus, these 2 virulence regulators-Mga and CsrRS—may account for the variation in M protein and hyaluronate content, respectively, observed in strains of a single M type. Spontaneous and experimentally engineered mutations in the CsrR system [ 71 , 77 ] can produce greatly enhanced infectivity in mice. Spontaneous mutations have been found in human infections as well.

For example, compared with mouse virulence of M3 strains isolated from subjects with ordinary pharyngitis, strains of M3 obtained from patients with streptococcal toxic shock exhibited greatly enhanced mouse virulence [ 77 ]. These strains were shown to contain a mutation with a deletion of the negative regulator csrR.

Mouse virulence correlated with the activity or actual levels of hyaluronic acid hasA and streptolysin S sagA , which is also regulated by csr R. In another study, GAS gene expression by an M1 virulent strain that produced experimental pharyngitis in monkeys was measured during 3 stages of infection incubation, acute inflammation, and convalescence. Colony morphology of throat cultures in these monkeys in different stages of infection, however, was not noted.

It was recently reported [ 79 ] that the prevalence of the M serotypes that were associated with rheumatic fever in Chicago in the s and s decreased significantly by the s.

However, encapsulation of the isolated M-typeable strains or other studies of strain virulence since those originally noted in the s [ 34 ] was not reported. Encapsulated organisms tend to persist in experimental pharyngeal infection in mice [ 66 , 80 ] and in baboons [ 81 ]. In the latter case, strains expressing M protein and capsule were carried for as long as 6 weeks, whereas those that were M protein and capsule negative persisted for only 14—21 days.

Noteworthy was the report from the Warren Air Force Base of GAS strains carried during convalescence from pharyngitis in an era when and in a locale where rheumatic fever and rheumatogenic strains were still prevalent [ 82 , 83 ]. In these studies of convalescent-phase carriage following untreated GAS pharyngitis, the infecting strain persisted as long as 2—3 months, eventually losing M protein and infectivity for monkeys.

Encapsulation of the persistently carried strains was not described. In conclusion, an argument may be made for renewed surveillance of colony morphology to support clinical management of GAS pharyngitis in cohorts at risk for post-infectious or invasive GAS diseases. The appearance of acute rheumatic fever, streptococcal toxic shock, or other invasive infections in a community should prompt close surveillance of positive culture results for the appearance of mucoid GAS colonies.

Such colonies may help to detect isolates that belong to new M serotypes or others that are not presently included in vaccines [ 87 ]. Financial support. Potential conflicts of interest. Google Scholar. Google Preview. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Encapsulation during Convalescent-Phase Carriage. Stollerman , Gene H.

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