Parallel Evolution of Group B
            <i>Streptococcus</i>
            Hypervirulent Clonal Complex 17 Unveils New Pathoadaptive Mutations

Almeida, Alexandre; Rosinski‐Chupin, Isabelle; Plainvert, Céline; Douarre, Pierre-Emmanuel; Borrego, Maria José; Poyart, Claire; Glaser, Philippe

doi:10.1128/msystems.00074-17

Cited by 32 publications

(43 citation statements)

References 64 publications

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“…GBS strains lacking a functional CovR ( covR) cause significantly greater cytotoxicity in neutrophils compared to wildtype (WT) GBS and isogenic non-pigmented/non-hemolytic mutants due to enhanced production of Granadaene (Lamy et al, 2004;Jiang et al, 2005;Rajagopal et al, 2006;Boldenow et al, 2016). Furthermore, GBS strains lacking CovR have been identified and isolated from women in preterm labor (Whidbey et al, 2013) and from patients with other GBS infectious morbidities (Sendi et al, 2009;Lupo et al, 2014;Almeida et al, 2015Almeida et al, , 2017Whidbey et al, 2015a). We hypothesized that L. lactis pcylX-K, which lacks transcriptional repressors specific to the cyl operon, would induce neutrophil cytotoxicity similar to GBS covR.…”

Section: Resultsmentioning

confidence: 99%

The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene

et al. 2020

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Group B Streptococcus (GBS) is a β-hemolytic, Gram-positive bacterium that commonly colonizes the female lower genital tract and is associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A major factor promoting GBS virulence is the β-hemolysin/cytolysin, which is cytotoxic to several host cells. We recently showed that the ornithine rhamnolipid pigment, Granadaene, produced by the gene products of the cyl operon, is hemolytic. Here, we demonstrate that heterologous expression of the GBS cyl operon conferred hemolysis, pigmentation, and cytoxicity to Lactococcus lactis, a model non-hemolytic Gram-positive bacterium. Similarly, pigment purified from L. lactis is hemolytic, cytolytic, and identical in structure to Granadaene extracted from GBS, indicating the cyl operon is sufficient for Granadaene production in a heterologous host. Using a systematic survey of phyletic patterns and contextual associations of the cyl genes, we identify homologs of the cyl operon in physiologically diverse Gram-positive bacteria and propose undescribed functions of cyl gene products. Together, these findings bring greater understanding to the biosynthesis and evolutionary foundations of a key GBS virulence factor and suggest that such potentially toxic lipids may be encoded by other bacteria.

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Section: Resultsmentioning

confidence: 99%

The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene

et al. 2020

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“…To complement the analysis, published whole genome sequence data of 4112 GBS isolates from previous studies was also included in this work (S5 Table). This was composed of isolates described by Da Cunha et al (n=228) [16], Rosini et al (n=127) [37], Flores et al (n=184) [33], Seale et al (n=1034) [38], Teatero et al (n=77) [20], Campisi et al (n=84) [22, 36], Almeida et al (n=192) [21, 23], Metcalf et al (n=2025) [15], and Kalimuddin et al (n=161) [24].…”

Section: Methodsmentioning

confidence: 99%

Temporal population structure of invasive Group BStreptococcusduring a period of rising disease incidence shows expansion of a CC17 clone

Jamrozy

Goffau

et al. 2018

Preprint

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21 Group B Streptococcus (GBS) is a major cause of neonatal invasive disease worldwide. In 22 the Netherlands, the incidence of the disease increased, despite the introduction of prevention 23 guidelines in 1999. This was accompanied by changes in pathogen genotype distribution, 24 with a significant increase in the prevalence of isolates belonging to clonal complex (CC) 17.25 To better understand the mechanisms of temporal changes in the epidemiology of GBS 26 genotypes that correlated with the rise in disease incidence, we applied whole genome 27 sequencing (WGS) to study a national collection of invasive GBS isolates. A total of 1345 28 isolates from patients aged 0 -89 days and collected between 1987 and 2016 in the 29 Netherlands were sequenced and characterised. The GBS population contained 5 major 30 lineages representing CC17 (39%), CC19 (25%), CC23 (18%), CC10 (9%), and CC1 (7%).31 There was a significant rise in the prevalence of isolates representing CC17 and CC23 among 32 cases of early-and late-onset disease, due to expansion of discrete sub-lineages. The most 33 prominent was shown by a CC17 sub-lineage, identified here as CC17-1A, which 34 experienced a major clonal expansion at the end of the 1990s. The CC17-1A expansion 35 correlated with the emergence of a novel phage carrying a gene encoding a putative adhesion 36 protein, named here StrP. The first occurrence of this phage (designated phiStag1) within the 37 collection in 1997, was followed by multiple, independent acquisitions by CC17 and parallel 38 clonal expansions of CC17-1A and another cluster, CC17-1B. The CC17-1A clone was 39 identified in external datasets, and represents a globally distributed invasive sub-lineage of 40 CC17. Our work describes how a sudden change in the epidemiology of specific GBS sub-41 lineages, in particular CC17-1A, correlates with the rise in the disease incidence, and 42 indicates a putative key role of a novel phage in driving the expansion of this CC17 clone. 43 3 44 Author summary45 Group B Streptococcus (GBS) is a commensal organism of the gastrointestinal and 46 genitourinary tracts. However, it is also an opportunistic pathogen and a major cause of 47 neonatal invasive disease, which can be classified into early-onset (0 -6 days of life) or late-48 onset (7 -89 days of life). Current disease prevention strategy involves intrapartum antibiotic 49 prophylaxis (IAP), which aims to prevent the transmission of GBS from mother to baby 50 during labour. Many developed countries adapted national IAP guidelines. In the 51 Netherlands, these were introduced in 1999. However, the incidence of GBS disease 52 increased after IAP introduction. In this study we applied whole genome sequencing to 53 characterise a nationwide collection of invasive GBS from cases of neonatal disease that 54 occurred between 1987 and 2016. Analysis of GBS population structure involving 55 phylogenetic partitioning of individual lineages revealed that the rise in disease incidence 56 involved the expansion of specific clusters from two ma...

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“…Also, work by Almeida et al reported a collection of mutations in the covS gene. These were primarily single amino acid substitutions (Thr43Ile, Ala87Val, Gly133Ser, His209Asn, Trp297Leu, and Glu337Ser) and the one double substitution (Trp297Cys and Gly298Trp) 41 . None of these amino acid changes were predicted amino acid changes in the covR and covS mutations found in our isolates suggesting mutations of covR and covS may occur in multiple locations in these genes.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and molecular analysis of nontypeable Group B streptococci: identification of cps2a and hybrid cps2a/cps5 Group B streptococcal capsule gene clusters

Alhhazmi

Tyrrell

2018

Emerging Microbes & Infections

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The Group B streptococcus (GBS) can express a capsular polysaccharide (CPS). There are ten recognized CPSs (Ia, Ib, and II–IX). A GBS isolate is considered nontypeable (NT) when CPS cannot be identified as one of ten types. Two groups of GBS NT isolates were studied, isolates without surface sialic acid (sia(−)) and isolates with surface sialic acid (sia(+)). The first objective was to characterize NT sia(−) isolates that failed CPS identification by an immunodiffusion antisera typing assay and a RT-PCR capsule typing assay. NT sia(−) isolates were characterized by assaying phenotypic changes and identifying covR/S mutations that may potentially have a role in the altered phenotypes. The second objective was to characterize NT sia(+) isolates that failed to identify as one of the ten CPS types by an immundiffusion antisera-based typing assay and a RT-PCR capsule typing assay yet expressed capsule. Fifteen NT sia(−) isolates displayed increased β hemolysis/orange pigmentation, decreased CAMP activity, inability to form biofilm, and susceptibility to phagocytosis by human blood. DNA sequence analysis of the covR/S genes in the sia(−) isolates found mutations in 14 of 15 isolates assayed. These mutations in the covR/S genes may potentially contribute to lack of expression of phenotypic traits assayed in vitro. For the three NT sia(+) isolates, whole-genome sequence analyses identified two isolates with cps gene clusters identical to the recently described and uncommon CPSIIa type. The third isolate possessed a hybrid cluster containing cps genes for both CPSIIa and CPSV suggesting recombination between these two gene clusters.

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Parallel Evolution of Group B Streptococcus Hypervirulent Clonal Complex 17 Unveils New Pathoadaptive Mutations

Cited by 32 publications

References 64 publications

The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene

The cyl Genes Reveal the Biosynthetic and Evolutionary Origins of the Group B Streptococcus Hemolytic Lipid, Granadaene

Temporal population structure of invasive Group BStreptococcusduring a period of rising disease incidence shows expansion of a CC17 clone

Phenotypic and molecular analysis of nontypeable Group B streptococci: identification of cps2a and hybrid cps2a/cps5 Group B streptococcal capsule gene clusters

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