Cross-Protection among Serotypes of Group A Streptococci (original) (raw)
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Nature Communications, 2020
Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation of cell-mediated immunity. SPy_2191 immunization significantly reduces streptococcal load in the organs and confers ~76-92% protection upon challenge with invasive GAS serotypes. Further, it significantly suppresses GAS pharyngeal colonization ...
Journal of Clinical Microbiology, 2005
Between July and October 2003, 121 clinical isolates of group A streptococci (GAS) were collected from a London hospital and characterized by multilocus sequence typing (MLST) to determine the identity and prevalence of clones circulating within this setting. A total of 39 sequence types (ST), of which 20 were represented by a single isolate, were identified. The eight most prevalent clones among the 121 GAS were ST117/emm81 (16%), ST39/emm4 (9%), ST62/emm87 (7%), ST28/emm1 (6%), ST36/emm12 (6%), ST46/emm22 (5%), ST334/emm82 (5%), and ST101/emm89 (4%). Compared to those in the MLST database (http://spyogenes.mlst.net), 12 (31%) of the 39 STs had not been previously identified, although 7 of these differed from recognized STs at only a single locus, suggesting they were closely related to previously recognized strains. Resistance to erythromycin and tetracycline was seen in 7 and 20% of isolates, respectively, with four isolates resistant to both agents. GAS strains with higher (>80) emm types accounted for 45% of GAS isolates collected during this study. Continuing GAS surveillance, using easily comparable methods, is important for detecting changes in the character of disease-causing isolates. Streptococcus pyogenes (group A streptococci [GAS]) is an important pathogen associated in humans with a variety of diseases, ranging from pharyngitis and impetigo to severe invasive disease, including streptococcal toxic shock syndrome and necrotizing fasciitis (10). In the late 1980s, concern about GAS disease was heightened in many countries, as outbreaks of more-severe clinical infection were reported (12). GAS infections remain a significant public health problem. In 2003, 1,870 cases of bacteremia due to GAS in England, Wales, and Northern Ireland were reported to the Health Protection Agency's Streptococcus and Diphtheria Reference Unit (20), an incidence of 3.5 per 100,000 population. Infections are largely treatable with appropriate antimicrobial therapy, although significant morbidity and mortality are reported for invasive GAS disease (34). Penicillin, to which GAS are uniformly susceptible, is the drug of choice for most infections with this organism (6). Erythromycin is recommended for treatment of penicillin-hypersensitive patients (6); however, resistance to this agent is of increasing concern (9, 25), and tetracycline can be used as an alternative in areas where resistance levels remain low (18). The development of an effective vaccine to prevent throat infections, which have a substantial economic cost and may occasionally lead to postinfectious sequelae and invasive disease (27), is highly desirable, and a number of vaccine targets are being assessed, including the highly variable immunogenic amino-terminal region of the M protein (11, 22). However, more than 100 M protein serotypes exist (16) and antibodies against this region offer type
Genetic variation in group A streptococci
International Journal of …, 2007
Group A streptococcus (GAS) is responsible for a range of human diseases that vary in their clinical manifestations and severity. While numerous virulence factors have been described, the way these factors interact to promote different streptococcal diseases is less clear. In order to identify multifactorial relationships between GAS and the human host, novel high-throughput techniques such as microarrays are necessary. We have performed comparative studies using custom-designed virulence arrays to enhance our understanding of the high degree of genotypic variation that occurs in streptococci. This study has pointed to mobile genetic elements as the major agents that promote variation. Our results show that multiple combinations of genes might bring about similar clinical pictures. This adds further complexity to the intricate relationship between pathogen and host.
The authors would like to dedicate this works to their families, friends, and students with love.
Journal of Experimental Medicine, 1980
The heterogeneity of a pepsin extract of type-24 M protein (pep M24) was demonstrated by absorption of type-specific and cross-reactive human antisera with M protein fragments and heterologous serotypes of M proteins, pepsin extract of type-5 M protein (pep M5) and pepsin extract of type-6 M protein (pep M6). 2 of 12 individuals immunized with pep M24 developed significant rises in antibody titers against pep M5 and pep M6, as measured by the enzyme-linked immunosorbent assay. The sam individuals also developed opsonic antibodies against type-6, but not type-5, streptococci, which suggested the development of cross-protective immunity. Inhibition studies of one of these sera with the heterologous pep M proteins showed that the cross-reactive antibodies against pep M6 could not be blocked by high concentrations of pep M24, the immunizing antigen; these antibodies could be blocked, however, by cyanogen bromide-derived peptide fragments of pep M24, which suggested that the cross-reacti...
Group A Streptococcus Infections: Their Mechanisms, Epidemiology, and Current Scope of Vaccines
Cureus
Group A streptococci (GAS) are gram-positive, cocci-shaped bacteria that cause a wide variety of infections and are a cause of significant health burden, particularly in lower-and middle-income nations. The GAS genome contains a number of virulence factors such as the M-protein, hyaluronic acid, C5a peptidase, etc. Despite its significant health burden across the globe, a proper vaccine against GAS infections is not yet available. Various candidates for an effective GAS vaccine are currently being researched. These are based on various parts of the streptococcal genome. These include candidates based on the N-terminal region of the M protein, the conserved C-terminal region of the M protein, and other parts of the streptococcal genome. The development of a vaccine against GAS infections is hampered by certain challenges, such as extensive genetic heterogeneity and high protein sequence variation. This review paper sheds light on the various virulence factors of GAS, their epidemiology, the different vaccine candidates currently being researched, and the challenges associated with M-protein and non-M-protein-based vaccines. This review also sheds light on the current scenario regarding the status of vaccine development against GAS-related infections.
Phenotypical characteristics of group B streptococcus in parturients
Brazilian Journal of Infectious Diseases, 2007
Colonization by Group B Streptococcus (GBS) is highly prevalent among pregnant women, with prevalence rates ranging between 4% and 30%. The infection may be transmitted vertically and may result in serious neonatal consequences. In the period from November 2003 to May 2004, a cross-sectional study was carried out among 316 parturients at the Jundiaí Teaching Hospital to establish the prevalence of genital GBS colonization, to identify the factors associated with colonization and the characteristic phenotypes of these streptococci. Samples from rectal and vaginal areas were collected for selective culture in Todd-Hewitt broth. Susceptibility to 7 antimicrobial agents was tested using the antibiotic diffusion disk technique, and the isolated strains were classified using specific antisera. The prevalence of GBS colonization was 14.6%. No strain was resistant to penicillin, ampicillin, erythromycin or nitrofurantoin. The majority of strains were sensitive to cephalothin. Greatest resistance was to gentamicin (76.1%), followed by clindamycin (17.4%). The most frequent serotype was Ib (23.9%), followed by serotypes II and Ia (19.6% and 17.4%, respectively). There was no correlation between serotype and greater antimicrobial resistance. In conclusion, the prevalence of GBS in parturients was high and penicillin continues to be the drug of choice for intrapartum prophylaxis. The most frequent serotype (Ib) found in this study differs from those found in the majority of studies carried out in other countries, revealing the need to identify prevalent serotypes in each region so that specific vaccines can be designed.
Inhibitor production by group-G streptococci of human and of animal origin
Journal of Medical Microbiology, 1983
Strains of group-G streptococci were tested by a "fingerprinting" method for the production of (P typing) and sensitivity to (S typing) inhibitory agents, and were biotyped. In the standard P-typing test, 28 of 50 strains of human origin, but none of 30 strains of animal origin, showed inhibitory activity. Of the human strains, 12 formed a bacteriocin that was active on group-A streptococci, including three (strains 12, I5 and 18) of the four streptococci of this group among the indicator strains. Sixteen other human strains inhibited the fourth group-A indicator (strain I7), and to a lesser extent strain 12, by lowering the pH of the typing medium. This acid-mediated inhibition was eliminated by testing on a medium containing calcium carbonate 0.5%; the 16 strains were then completely non-inhibitory, and the bacteriocinforming strains, the typing pattern of which had originally been 12,15, 17, 18, showed only inhibition attributable to the action of the bacteriocin. Nearly all group-A streptococci were sensitive to the group-G bacteriocin. The indicator strain I7 and several other members of M-type 28 were exceptions, but their resistance was not associated with the presence of R-antigen 28. Fifteen inhibitor-sensitivity patterns and 12 biotypes were identified among the strains; some of these tended to be associated with either a human or an animal origin. Neither S type nor biotype appeared to correlate with inhibitor production.
A study of some motile group D streptococci
Journal of general microbiology, 1967
Thirteen strains of motile enterococci showed more similarity, in their physiological reactions, to Streptococcus faecium than to S. faecalis. A serological study of the type antigens divided the motile strains into four sets ; ( I ) three strains previously described as S. faecium serotype 29, (2) one strain reacting as S. faeciurn serotype 38, (3) five strains showing a specific reaction with antiserum prepared to one of them ('serotype 4725'), (4) four untyped strains. Esterase and protein patterns from the soluble fractions of the motile strains were examined by electrophoresis in polyacrylamide gel and were different from those of non-motile strains of S. faecalis, S. faecium and S. durans. Extracts of the three motile strains of S. faecium type 29 showed a common esterase pattern, extracts from five strains of serotype 4725 showed three different esterase patterns. The motile strain of S. faecium serotype 38 gave extracts with a strong esterase band which differed from the very weak bands shown by extracts of non-motile strains. Differences in esterase pattern could be found between motile strains whether untyped, of different serotypes, or of the same serotype. Comparison of the 'protein patterns' of motile strains gave some indication that major protein bands occurred at similar positions after electrophoresis.
Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes
Clinical and Vaccine Immunology, 2005
Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.