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Age-stratified analysis of serotype-specific baseline immunity against group B streptococcus.

ABSTRACT: Group B streptococcus (GBS) vaccines are currently under development. Data on the natural immunity in diverse age groups will aid establishing the GBS immunization policy. In this study, thirty serum samples were collected from three age groups (neonates/infants, pregnant women, and the elderly) between August 2016 and July 2017. Serotype-specific opsonophagocytic activity (OPA) was assessed using a GBS multiplex opsonophagocytic killing assay (MOPA) against serotypes Ia, III, and V. The mean OPA titers for serotype Ia of the three age groups were not significantly different (p = .156), but tended to be lower in neonates/infants (mean ± standard deviation, 137 ± 278). For serotype III and V, the mean OPA titer of neonates/infants (338 ± 623 and 161 ± 445, respectively) was significantly lower than that of pregnant women (1377 ± 1167 and 9414 ± 6394) and the elderly (1350 ± 1741 and 3669 ± 5597) (p = .002). In conclusion, the lower levels of OPA titers against all tested serotypes in neonates/infants, despite high maternal titers, indicates that intrapartum GBS vaccinations may be required for efficient placental transfer of serotype-specific GBS antibodies with high avidity.

SUBMITTER: Choi MJ

PROVIDER: S-EPMC7482737 | biostudies-literature |

REPOSITORIES: biostudies-literature

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RocA has serotype-specific gene regulatory and pathogenesis activity in serotype M28 group A streptococcus

Project description:RNA-seq experiments of a wild-type and isogenic rocA deletion mutant serotype M28 group A streptococcus strain at two time points

2018-08-27 | GSE118609 | GEO

RocA Has Serotype-Specific Gene Regulatory and Pathogenesis Activities in Serotype M28 Group A Streptococcus.

Project description:Serotype M28 group A streptococcus (GAS) is a common cause of infections such as pharyngitis ("strep throat") and necrotizing fasciitis ("flesh-eating" disease). Relatively little is known about the molecular mechanisms underpinning M28 GAS pathogenesis. Whole-genome sequencing studies of M28 GAS strains recovered from patients with invasive infections found an unexpectedly high number of missense (amino acid-changing) and nonsense (protein-truncating) polymorphisms in rocA (regulator of Cov), leading us to hypothesize that altered RocA activity contributes to M28 GAS molecular pathogenesis. To test this hypothesis, an isogenic rocA deletion mutant strain was created. Transcriptome sequencing (RNA-seq) analysis revealed that RocA inactivation significantly alters the level of transcripts for 427 and 323 genes at mid-exponential and early stationary growth phases, respectively, including genes for 41 transcription regulators and 21 virulence factors. In contrast, RocA transcriptomes from other GAS M protein serotypes are much smaller and include fewer transcription regulators. The rocA mutant strain had significantly increased secreted activity of multiple virulence factors and grew to significantly higher colony counts under acid stress in vitro RocA inactivation also significantly increased GAS virulence in a mouse model of necrotizing myositis. Our results demonstrate that RocA is an important regulator of transcription regulators and virulence factors in M28 GAS and raise the possibility that naturally occurring polymorphisms in rocA in some fashion contribute to human invasive infections caused by M28 GAS strains.

| S-EPMC6204712 | biostudies-literature

Use of a serotype-specific DNA microarray for identification of group B Streptococcus (Streptococcus agalactiae).

Project description:Group B Streptococcus (GBS; Streptococcus agalactiae) is an important cause of sepsis and meningitis. Nine GBS serotypes, based on capsular polysaccharide (CPS) antigens, have been described. Their distribution varies worldwide and needs to be monitored to understand the epidemiology of GBS disease and inform the development of vaccines. In this study, we sequenced cpsH of GBS serotype II (cpsHII) and compared it with that of the other eight serotypes to identify serotype-specific regions. We then developed a DNA microarray based on the cpsH gene and used it to test 88 GBS isolates-9 serotype reference strains and 79 clinical isolates-and 7 other bacterial and fungal species which are commonly present in the vagina flora. The microarray was shown to be specific and reproducible. This is the first report of a microarray which can identify the nine GBS serotypes. The use of a microarray has advantages over traditional serotyping methods and will be of practical value in both reference and diagnostic laboratories.

| S-EPMC1448623 | biostudies-literature

RNAseq analysis of the serotype M1 group A Streptococcus strain MGAS2221

Project description:We recovered RNA from exponential and stationary phase cell cultures of MGAS2221 and utilized two distinct methods to remove rRNA from our samples, the RiboZero kit from Epicenter, and the terminator- 5--Phosphate-Dependent Exonuclease (TEX). This gave us 4 distinct RNAs with which we performed RNAseq analysis. Both rRNA removal methods worked well, with only a small percentage of the final total read counts being derived from rRNA sequences.

2013-03-20 | GSE45325 | GEO

Identification and Characterization of Serotype-Specific Variation in Group A Streptococcus Pilus Expression.

Project description:Isolates of a given bacterial pathogen often display phenotypic variation, and this can negatively impact public health, for example, by reducing the efficacy of preventative measures. Here, we identify that the human pathogen group A Streptococcus (GAS; Streptococcus pyogenes) expresses pili on its cell surface in a serotype-specific manner. Specifically, we show that serotype M3 GAS isolates, which are nonrandomly associated with causing particularly severe and lethal invasive infections, produce negligible amounts of pili relative to serotype M1 and M49 isolates. Performance of an interserotype transcriptome comparison (serotype M1 versus serotype M3) was instrumental in this discovery. We also identified that the transcriptional regulator Nra positively regulates pilus expression in M3 GAS isolates and that the low level of pilus expression of these isolates correlates with a low level of nra transcription. Finally, we discovered that the phenotypic consequences of low levels of pilus expression by M3 GAS isolates are a reduced ability to adhere to host cells and an increased ability to survive and proliferate in human blood. We propose that an enhanced ability to survive in human blood, in part due to reduced pilus expression, is a contributing factor in the association of serotype M3 isolates with highly invasive infections. In conclusion, our data show that GAS isolates express pili in a serotype-dependent manner and may inform vaccine development, given that pilus proteins are being discussed as possible GAS vaccine antigens.

| S-EPMC5778356 | biostudies-literature

Genome-wide analysis of an avirulent strain that induces protective immunity against challenge with virulent Streptococcus suis serotype 2.

Project description:It was previously reported in China that two recent large-scale outbreaks of Streptococcus suis serotype 2 (S. suis 2) infections in human were caused by two highly virulent S. suis 2 strains, from which a novel genomic island (GEI), associated with disease onset and progression and designated 89 K, was identified. Here, an avirulent strain, 05HAS68, was isolated from a clinically healthy pig.By comparing the genomes of this avirulent strain with virulent strains, it was found that massive genomic rearrangements occurred, resulting in alterations in gene expression that caused enormous single gene gain and loss. Important virulent genes were lost, such as extracellular protein factor (ef) and suilysin (sly) and larger mutants, such as muramidase-released protein (mrp). Piglets vaccinated with the avirulent strain, 05HAS68, had increased TNF-? and IFN-? levels in the peripheral blood and were fully protected from challenge infection with the most virulent S. suis 2 strain, 05ZYH33. Transfusion of T cells and plasma from vaccinated pigs resulted in protection of recipient animals against the 05ZYH33 challenge.These results suggest that analysis genome of the avirulent strains are instrumental in the development of vaccines and for the functional characterization of important of genetic determinants.

| S-EPMC5351164 | biostudies-literature

Regulatory Rewiring Confers Serotype-Specific Hyper-Virulence in the Human Pathogen Group A Streptococcus

Project description:We sequenced mRNA transcripts from three isogenic M3 serotype GAS strains, parental (MGAS10870), complement (10870::rocAM1), and deletion (10870ΔrocA). There were no significant changes between the parental and revertant strain. Comparison of the parental and complemented strain revealed several virulence factors were up-regulated in the parental strain where RocA function was diminished. We concluded that RocA, through direct or indirect mechanisms, is able to control numerous virulence genes and this lack of RocA regulation increases expression of virulence factors, which contributes to the hyper-virulent state of serotype M3 GAS.

2015-08-24 | GSE68277 | GEO

Regulatory rewiring confers serotype-specific hyper-virulence in the human pathogen group A Streptococcus.

Project description:Phenotypic heterogeneity is commonly observed between isolates of a given pathogen. Epidemiological analyses have identified that some serotypes of the group A Streptococcus (GAS) are non-randomly associated with particular disease manifestations. Here, we present evidence that a contributing factor to the association of serotype M3 GAS isolates with severe invasive infections is the presence of a null mutant allele for the orphan kinase RocA. Through use of RNAseq analysis, we identified that the natural rocA mutation present within M3 isolates leads to the enhanced expression of more than a dozen immunomodulatory virulence factors, enhancing phenotypes such as hemolysis and NAD(+) hydrolysis. Consequently, an M3 GAS isolate survived human phagocytic killing at a level 13-fold higher than a rocA complemented derivative, and was significantly more virulent in a murine bacteremia model of infection. Finally, we identified that RocA functions through the CovR/S two-component system as levels of phosphorylated CovR increase in the presence of functional RocA, and RocA has no regulatory activity following covR or covS mutation. Our data are consistent with RocA interfacing with the CovR/S two-component system, and that the absence of this activity in M3 GAS potentiates the severity of invasive infections caused by isolates of this serotype.

| S-EPMC4675629 | biostudies-literature

RNAseq analysis of the serotype M1 group A Streptococcus strain MGAS2221

2013-03-20 | E-GEOD-45325 | biostudies-arrayexpress

Serotype-specific acquisition and loss of group B streptococcus recto-vaginal colonization in late pregnancy.

Project description:BackgroundMaternal recto-vaginal colonization with Group B Streptococcus (GBS) and consequent vertical transmission to the newborn predisposes neonates to early-onset invasive GBS disease. This study aimed to determine the acquisition and loss of serotype-specific recto-vaginal GBS colonization from 20-37+ weeks of gestational age.MethodsVaginal and rectal swabs were collected from HIV-uninfected women at 20-25 weeks of gestation age and at 5-6 weekly intervals thereafter. Swabs were cultured for GBS and isolates were serotyped by latex agglutination. Serologically non-typable isolates and pilus islands were characterized by PCR.ResultsThe prevalence of recto-vaginal GBS colonization was 33.0%, 32.7%, 28.7% and 28.4% at 20-25 weeks, 26-30 weeks, 31-35 weeks and 37+ weeks of gestational age, respectively. The most common identified serotypes were Ia (39.2%), III (32.8%) and V (12.4%). Of 507 participants who completed all four study visits, the cumulative overall recto-vaginal acquisition rate of new serotypes during the study was 27.9%, including 11.2%, 8.2% and 4.3% for serotypes Ia, III and V, respectively. Comparing the common colonizing serotypes, serotype III was more likely to be associated with persistent colonization throughout the study (29%) than Ia (18%; p?=?0.045) or V (6%; p?=?0.002). The median duration of recto-vaginal GBS colonization for serotype III was 6.35 weeks, which was longer than other serotypes. Pilus island proteins were detected in all GBS isolates and their subtype distribution was associated with specific serotypes.ConclusionSouth African pregnant women have a high prevalence of GBS recto-vaginal colonization from 20 weeks of gestational age onwards, including high GBS acquisition rates in the last pregnancy-trimesters. There are differences in specific-serotype colonization patterns during pregnancy.

| S-EPMC4076185 | biostudies-literature

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