Genomic Analysis Reveals Multi-Drug Resistance Clusters in Group B Streptococcus CC17 Hypervirulent Isolates Causing Neonatal Invasive Disease in Southern Mainland China

Campisi, Edmondo; Rosini, Roberto; Ji, Wenjing; Guidotti, Silvia; Rojas-López, Maricarmen; Geng, Guoxia; Deng, Qiulian; Zhong, Huamin; Wang, Weidong; Liu, Haiying; Nan, Cassandra; Margarit, Immaculada; Rinaudo, C. Daniela

doi:10.3389/fmicb.2016.01265

Cited by 43 publications

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“…A recent study from Canada, using whole genome sequencing analysis, revealed the loss of PI-1 in a group of CC17 isolates and integration in the same genomic location of a mobile genetic element carrying multiple antimicrobial resistance genes (Teatero et al, 2016). Another recent publication from China confirmed and extended these findings, further discriminating the CC17/PI-2b isolates into two groups, distinguishable by their antimicrobial resistance profiles, namely lincomycin resistance associated with the presence of lnu (B) gene (Campisi et al, 2016). In our subset of CC17/PI-2b, all but two isolates were simultaneously resistant to erythromycin, clindamycin, tetracycline and streptomycin, and carried the erm ( B ), tet ( O ), aph ( 3 ′)- II, and ant(6)-Ia genes (Table 2).…”

Section: Discussionmentioning

confidence: 76%

“…In our subset of CC17/PI-2b, all but two isolates were simultaneously resistant to erythromycin, clindamycin, tetracycline and streptomycin, and carried the erm ( B ), tet ( O ), aph ( 3 ′)- II, and ant(6)-Ia genes (Table 2). We found that our CC17/PI-2b also presented resistance to kanamycin and lincomycin, which would place them in the lincomycin resistant sublineage according to Campisi (Campisi et al, 2016). However, none of the our isolates harbored the lnu (B) gene, raising the possibility that our strains represent yet another sublineage of CC17/PI-2b.…”

Section: Discussionmentioning

confidence: 78%

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Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005–2015): Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage

et al. 2017

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The molecular characterization of 218 GBS isolates recovered from neonatal invasive infections in Portugal in 2005–2015 revealed the existence of a small number of genetically distinct lineages that were present over a significant time-span. Serotypes III and Ia were dominant in the population, together accounting for >80% of the isolates. Clonal complex 17 included 50% of all isolates, highlighting the importance of the hypervirulent genetic lineage represented by serotype III ST17/rib/PI-1+PI-2b. Serotype Ia was represented mainly by ST23, previously reported as dominant among invasive disease in non-pregnant adults in Portugal, but also by ST24, showing an increased frequency among late-onset disease. Overall erythromycin resistance was 16%, increasing during the study period (p < 0.001). Macrolide resistance was overrepresented among CC1 and CC19 isolates (p < 0.001 and p = 0.008, respectively). While representatives of the hypervirulent CC17 lineage were mostly susceptible to macrolides, we identified for the first time in Europe a recently emerging sublineage characterized by the loss of PI-1 (CC17/PI-2b), simultaneously resistant to macrolides, lincosamides, and tetracycline, also exhibiting high-level resistance to streptomycin and kanamycin. The stability and dominance of CC17 among neonatal invasive infections in the past decades indicates that it is extremely well adapted to its niche; however emerging resistance in this genetic background may have significant implications for the prevention and management of GBS disease.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 78%

Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005–2015): Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage

et al. 2017

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“…Particular focus on the epidemiology of the expanding CC17-1A sub-lineage is also warranted. We identified the presence of this clone in other GBS collections including a high prevalence amongst invasive isolates from China and Canada [20, 36]. Further international genomic GBS surveillance data is needed to better understand the contribution of CC17-1A sub-lineage to the burden of GBS invasive disease in newborns outside of the Netherlands.…”

Section: Discussionmentioning

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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“…The PI-2b pilus was primarily associated with the epidemiologically relevant clinical isolates belonging to CC17, but was not strictly restricted to this “hypervirulent” lineage causing the majority of neonatal invasive diseases. Two genomic studies investigating several contemporary CC17 isolates from Canada and South China demonstrated conservation of the PI-2b locus but loss of the PI-1 pilus which is replaced by novel mobile genetic elements encoding determinants of antimicrobial resistance [9, 24]. Unlike the other two pilus loci PI-1 and PI-2a, no regulatory gene was found in the vicinity of PI-2b and the regulation of PI-2b expression has not been studied so far.…”

Section: Discussionmentioning

confidence: 99%

Regulation of PI-2b Pilus Expression in Hypervirulent Streptococcus agalactiae ST-17 BM110

et al. 2017

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The widely spread Streptococcus agalactiae (also known as Group B Streptococcus, GBS) “hypervirulent” ST17 clone is strongly associated with neonatal meningitis. The PI-2b locus is mainly found in ST17 strains but is also present in a few non ST17 human isolates such as the ST-7 prototype strain A909. Here, we analysed the expression of the PI-2b pilus in the ST17 strain BM110 as compared to the non ST17 A909. Comparative genome analyses revealed the presence of a 43-base pair (bp) hairpin-like structure in the upstream region of PI-2b operon in all 26 ST17 genomes, which was absent in the 8 non-ST17 strains carrying the PI-2b locus. Deletion of this 43-bp sequence in strain BM110 resulted in a 3- to 5-fold increased transcription of PI-2b. Characterization of PI-2b promoter region in A909 and BM110 strains was carried out by RNAseq, primer extension, qRT-PCR and transcriptional fusions with gfp as reporter gene. Our results indicate the presence of a single promoter (Ppi2b) with a transcriptional start site (TSS) mapped 37 bases upstream of the start codon of the first PI-2b gene. The large operon of 16 genes located upstream of PI-2b codes for the group B carbohydrate (also known as antigen B), a major constituent of the bacterial cell wall. We showed that the hairpin sequence located between antigen B and PI-2b operons is a transcriptional terminator. In A909, increased expression of PI-2b probably results from read-through transcription from antigen B operon. In addition, we showed that an extended 5’ promoter region is required for maximal transcription of gfp as a reporter gene in S. agalactiae from Ppi2b promoter. Gene reporter assays performed in Lactococcus lactis strain NZ9000, a related non-pathogenic Gram-positive species, revealed that GBS-specific regulatory factors are required to drive PI-2b transcription. PI-2b expression is up-regulated in the BM110ΔcovR mutant as compared to the parental BM110 strain, but this effect is probably indirect. Collectively, our results indicate that PI-2b expression is regulated in GBS ST17 strains, which may confer a selective advantage in the human host either by reducing host immune responses and/or increasing their dissemination potential.

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Genomic Analysis Reveals Multi-Drug Resistance Clusters in Group B Streptococcus CC17 Hypervirulent Isolates Causing Neonatal Invasive Disease in Southern Mainland China

Cited by 43 publications

References 50 publications

Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005–2015): Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage

Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005–2015): Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage

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

Regulation of PI-2b Pilus Expression in Hypervirulent Streptococcus agalactiae ST-17 BM110

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