Population genomics reveals distinct temporal association with the emergence of ST1 serotype V Group B Streptococcus and macrolide resistance in North America

2021 ◽  
Author(s):  
M. Belén Cubria ◽  
Luis Alberto Vega ◽  
William C. Shropshire ◽  
Misu A. Sanson ◽  
Brittany J. Shah ◽  
...  
Keyword(s):  
Population Genomics ◽  
Young Infant ◽  
Mobile Genetic Elements ◽  
Invasive Disease ◽  
Macrolide Resistance ◽  
Temporal Association ◽  
Bacterial Disease ◽  
Genetic Elements ◽  
Young Infants ◽  
Group B

Identified in the 1970s as the leading cause of invasive bacterial disease in neonates and young infants, Group B Streptococcus (GBS) is now also recognized as a significant cause of morbidity and mortality among adults with underlying medical conditions and the elderly. Concomitant with the increasing incidence of GBS invasive disease in adults is the rise of resistance among GBS isolates to second line antibiotics. Previous research shows that among serotype V GBS – one of the most common capsular types causing adult invasive disease – sequence type 1 (ST1) – accounts for an overwhelming majority of adult invasive disease isolates and frequently harbors macrolide resistance. In this study, using whole genome sequencing data from strains isolated in the USA and Canada over a 45-year period, we examined the association of antimicrobial resistance with the emergence of invasive serotype V ST1 GBS. Our findings show a strong temporal association between increased macrolide resistance and the emergence of serotype V ST1 GBS subpopulations that currently co-circulate to cause adult as well as young infant invasive disease. ST1 GBS subpopulations are defined, in part, by the presence of macrolide resistance genes in mobile genetic elements. Increased frequency of macrolide resistance-encoding mobile genetic elements among invasive GBS ST1 strains suggests the presence of such elements contributes to GBS virulence. Our work provides a foundation for the investigation of genetic features contributing to the increasing prevalence and pathogenesis of serotype V GBS in adult invasive disease.

scholarly journals Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001–2015

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191193 ◽  
Author(s):  
Betuel Sigaúque ◽  
Miwako Kobayashi ◽  
Delfino Vubil ◽  
Ariel Nhacolo ◽  
Alberto Chaúque ◽  
...  
Keyword(s):  
Bacterial Disease ◽  
Young Infants ◽  
Group B

scholarly journals Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae

2015 ◽  
Vol 6 ◽  
Author(s):  
Scott T. Chancey ◽  
Sonia Agrawal ◽  
Max R. Schroeder ◽  
Monica M. Farley ◽  
Hervé Tettelin ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mobile Genetic Elements ◽  
Macrolide Resistance ◽  
Genetic Elements

scholarly journals Surveillance of Macrolide-Resistant Mycoplasma pneumoniae in Beijing, China, from 2008 to 2012

2012 ◽  
Vol 57 (3) ◽  
pp. 1521-1523 ◽  
Author(s):  
Fei Zhao ◽  
Gang Liu ◽  
Jiang Wu ◽  
Bin Cao ◽  
Xiaoxia Tao ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Mobile Genetic Elements ◽  
Macrolide Resistance ◽  
Content Type ◽  
Genetic Elements ◽  
Resistance Rates ◽  
Beijing China

ABSTRACTMacrolide resistance rates ofMycoplasma pneumoniaein the Beijing population were as high as 68.9%, 90.0%, 98.4%, 95.4%, and 97.0% in the years 2008 to 2012, respectively. Common macrolide-resistant mobile genetic elements were not detected with any isolate. These macrolide-resistant isolates came from multiple clones rather than the same clone. No massive aggregation of a particular clone was found in a specific period.

scholarly journals Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2355 ◽  
Author(s):  
Miwako Kobayashi ◽  
Johan Vekemans ◽  
Carol J. Baker ◽  
Adam J. Ratner ◽  
Kirsty Le Doare ◽  
...  
Keyword(s):  
At Risk ◽  
Disease Burden ◽  
Vaccine Development ◽  
Young Infant ◽  
Group B Streptococcus ◽  
Current Status ◽  
Middle Income ◽  
Young Infants ◽  
Group B ◽  
Low And Middle Income

Globally, group BStreptococcus(GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation.This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations.

scholarly journals The Association Between Breast Milk Group B Streptococcal Capsular Antibody Levels and Late-onset Disease in Young Infants

2019 ◽  
Author(s):  
Ziyaad Dangor ◽  
Mahtaab Khan ◽  
Gaurav Kwatra ◽  
Alane Izu ◽  
Firdose Nakwa ◽  
...  
Keyword(s):  
Breast Milk ◽  
Late Onset ◽  
Immunoglobulin A ◽  
Invasive Disease ◽  
Human Immunodeficiency Virus Status ◽  
Model Studies ◽  
Milk Samples ◽  
Young Infants ◽  
Group B ◽  
Gastrointestinal Colonization

Abstract Background Animal-model studies have demonstrated less group B streptococcal (GBS) invasive disease and gastrointestinal colonization after enteral administration of serotype-specific capsular antibodies. There is, however, a paucity of information on the association of breast milk GBS serotype-specific capsular antibodies and risks for invasive disease in infants. The aim of this study was to explore the association between natural secretory immunoglobulin A (sIgA) capsular antibodies in breast milk and the occurrence of late-onset disease (LOD) in young infants. Methods A matched case-control study was undertaken in infants <3 months of age in Johannesburg, South Africa. Breast milk samples were collected on cases and controls matched for gestational age, maternal age, and human immunodeficiency virus status at time of enrollment. Capsular serotype Ia, Ib, III, and V sIgA antibody concentrations were measured using the fluorescence-based micro-bead immunosorbent assay. Results Breast milk samples were available for 31 LOD cases (8 serotype Ia and 23 serotype III), 21 recto-vaginally colonized matched controls (10 serotype Ia and 11 serotype III), and 84 serotype Ia and 105 serotype III noncolonized matched controls. Using a Bayesian model to estimate the probability of disease, there were 90% reductions in the risks of developing serotypes Ia and III LOD with sIgA concentrations ≥0.14 µg/mL and ≥2.52 µg/mL, respectively. Conclusions Breast milk sIgA capsular antibodies were associated with lower risks for LOD in young infants. The ability of GBS polysaccharide-protein conjugate vaccines currently under development to induce sIgA responses warrant investigation as potential mediators of protection against LOD.

scholarly journals Towards a genotyping system for Streptococcus agalactiae (group B streptococcus): use of mobile genetic elements in Australasian invasive isolates

2003 ◽  
Vol 52 (4) ◽  
pp. 337-344 ◽  
Author(s):  
Fanrong Kong ◽  
Diana Martin ◽  
Gregory James ◽  
Gwendolyn L. Gilbert
Keyword(s):  
Streptococcus Agalactiae ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Surface Protein ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Gene Profiles ◽  
Polysaccharide Synthesis ◽  
Genetic Clusters ◽  
Group B

This study forms part of the development of an integrated genotyping system for Streptococcus agalactiae (group B streptococcus, GBS) that can be used to study the population genetics of the organism and the pathogenesis and epidemiology of GBS disease. In recent previous studies, two sets of markers, the capsular polysaccharide synthesis (cps) gene cluster and surface protein antigen genes, have been used to assign molecular serotypes (MS) and protein-gene profiles (PGP) to more than 200 isolates. In the present study, five mobile genetic elements (MGE) have been used as a third set of markers, to characterize further 194 invasive isolates, recovered from blood or cerebrospinal fluid (CSF). Of these, 97 % contained one or more of the five MGE, the distribution of which was related to MS and PGP, as illustrated by MS III, which is divisible into four serosubtypes with different combinations of the MGE (or none). Fifty-six different genotypes and eight genetic clusters were identified, each with different combinations of the three sets of molecular markers. Five predominant genotypes (Ia-1, Ib-1, III-1, III-2 and V-1) contained 62 % of the isolates and five of the eight genetic clusters contained 92 % of the isolates. The 17 CSF isolates were relatively widely distributed between 10 genotypes and across seven of the eight clusters. Further study is needed to determine whether these genotypes or clusters share common markers of increased virulence. In future, comparison of invasive with colonizing strains of GBS may elucidate the significance of these findings.

The novel macrolide resistance genes mef(F) and msr(G) are located on a plasmid in Macrococcus canis and a transposon in Macrococcus caseolyticus

2020 ◽  
Vol 76 (1) ◽  
pp. 48-54
Author(s):  
Javier Eduardo Fernandez ◽  
Vincent Perreten ◽  
Sybille Schwendener
Keyword(s):  
Resistance Genes ◽  
Resistance Mechanism ◽  
Mobile Genetic Elements ◽  
Bioinformatic Analysis ◽  
Membered Ring ◽  
Macrolide Resistance ◽  
The Novel ◽  
Bacterial Strains ◽  
Chloramphenicol Resistance ◽  
Genetic Elements

Abstract Objectives To analyse macrolide resistance in a Macrococcus canis strain isolated from a dog with an ear infection, and determine whether the resistance mechanism is also present in other bacteria, and associated with mobile genetic elements. Methods The whole genome of M. canis Epi0082 was sequenced using PacBio and Illumina technologies. Novel macrolide resistance determinants were identified through bioinformatic analysis, and functionality was demonstrated by expression in Staphylococcus aureus. Mobile genetic elements containing the novel genes were analysed in silico for strain Epi0082 as well as in other bacterial strains deposited in GenBank. Results M. canis Epi0082 contained a 3212 bp operon with the novel macrolide resistance genes mef(F) and msr(G) encoding a efflux protein and an ABC-F ribosomal protection protein, respectively. Cloning in S. aureus confirmed that both genes individually confer resistance to the 14- and 15-membered ring macrolides erythromycin and azithromycin, but not the 16-membered ring macrolide tylosin. A reduced susceptibility to the streptogramin B pristinamycin IA was additionally observed when msr(G) was expressed in S. aureus under erythromycin induction. Epi0082 carried the mef(F)–msr(G) operon together with the chloramphenicol resistance gene fexB in a novel 39 302 bp plasmid pMiCAN82a. The mef(F)–msr(G) operon was also found in macrolide-resistant Macrococcus caseolyticus strains in the GenBank database, but was situated in the chromosome as part of a novel 13 820 bp or 13 894 bp transposon Tn6776. Conclusions The identification of mef(F) and msr(G) on different mobile genetic elements in Macrococcus species indicates that these genes hold potential for further dissemination of resistance to the clinically important macrolides in the bacterial population.

scholarly journals 855. Evolution of Group B Streptococcal Capsular Type V Invasive Infections in Neonates and Young Infants: A Whole Genome Sequencing Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S19-S19
Author(s):  
Anthony R Flores ◽  
Misu A Sanson ◽  
Brittany J Shah ◽  
Marcia Rench ◽  
Samuel A Shelburne ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Capsular Polysaccharide ◽  
Young Infant ◽  
Low Frequency ◽  
Tetracycline Resistance ◽  
Illumina Miseq ◽  
Young Infants ◽  
Antimicrobial Resistance Gene ◽  
Group B ◽  
Type V

Abstract Background Since 1970 group B Streptococcus (GBS) has been a frequent cause of sepsis or meningitis in young infants. Capsular polysaccharide type V was first recognized in 1990 and has increased to the point where it now causes ~15% of GBS infections. GBS type V strains are almost entirely sequence type 1 (ST1) in adult infections. To understand the emergence of type V GBS, we compared infant strains before 1990 to more contemporary isolates from young infants and adults. Methods Thirty-five strains isolated from blood or CSF of infants <90 days of age (Houston, 1979–1996) were compared with the following previously sequenced type V, ST1 strains: (1) 14 from infant blood or CSF from Center for Disease Control and Prevention (CDC) (2015–2017), (2) 193 blood ST1 isolates from adults (Houston, 1992–2013), and (3) 516 invasive isolates from the CDC (2015–2017). Isolates were sequenced using an Illumina MiSeq instrument followed by molecular typing, antimicrobial resistance gene determination, and phylogenetic analysis. Antimicrobial susceptibility testing (AST) was performed using disk diffusion and E-test. Results The majority (29/35) of Houston young infant strains were ST1. Type V GBS strains isolated prior to 1990 were more likely to be of ST-2 or ST-26 (5/10) compared with those from 1990 or later (24/25 and 14/14 CDC infant invasive type V). Tetracycline resistance was identified in 83% (29/35) while macrolide resistance (MR) occurred in only 23% (8/35) of the strains. Compared with early neonatal isolates, MR was significantly more frequent among contemporary neonatal (12/14, 86%, P < 0.0001) and adult (502/710, 71%, P < 0.0001) ST1 GBS. Phylogenetic analysis showed two distinct clades defined, in part, by MR. A high-frequency MR (340/360, 94%) clade was defined by the presence of erm(B) on Tn3872 while the low-frequency MR clade (159/350, 45%) was more diverse in mobile elements contributing to MR. The majority (27/29) of early neonatal ST1 GBS strains were observed in the low-frequency MR clade. Conclusion Infant invasive disease due to type V GBS before 1990 consisted of more diverse STs but is now almost exclusively ST1. Differences in the frequency of MR between early neonatal and contemporary type V ST1 GBS suggest MR may, at least in part, have driven the expansion of type V ST1 GBS. Disclosures All Authors: No reported Disclosures.

scholarly journals Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015

2018 ◽  
Vol 23 (21) ◽  
Author(s):  
Elísia Lopes ◽  
Tânia Fernandes ◽  
Miguel P Machado ◽  
João André Carriço ◽  
José Melo-Cristino ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Recombination Event ◽  
Surface Protein ◽  
Invasive Disease ◽  
Macrolide Resistance ◽  
Gene Profiling ◽  
Genetic Lineage ◽  
Group B ◽  
Resistance Rates ◽  
Lancefield Group

We characterised Lancefield group B streptococcal (GBS) isolates causing invasive disease among non-pregnant adults in Portugal between 2009 and 2015. All isolates (n = 555) were serotyped, assigned to clonal complexes (CCs) by multilocus sequence typing and characterised by surface protein and pilus island gene profiling. Antimicrobial susceptibility was tested by disk diffusion and resistance genotypes identified by PCR. Overall, serotype Ia was most frequent in the population (31%), followed by serotypes Ib (24%) and V (18%). Serotype Ib increased significantly throughout the study period (p < 0.001) to become the most frequent serotype after 2013. More than 40% of isolates clustered in the CC1/alp3/PI-1+PI-2a genetic lineage, including most isolates of serotypes Ib (n = 110) and V (n = 65). Erythromycin and clindamycin resistance rates were 35% and 34%, respectively, both increasing from 2009 to 2015 (p < 0.010) and associated with CC1 and serotype Ib (p < 0.001). The Ib/CC1 lineage probably resulted from acquisition of the type Ib capsular operon in a single recombination event by a representative of the V/CC1 macrolide-resistant lineage. Expansion of the new serotype Ib/CC1 lineage resulted in increased macrolide resistance in GBS, causing invasive disease among adults in Portugal. The presence of this clone elsewhere may predict more widespread increase in resistance.

scholarly journals Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp inKlebsiella pneumoniaepopulations

2017 ◽  
Author(s):  
Margaret M. C. Lam ◽  
Ryan R. Wick ◽  
Kelly L. Wyres ◽  
Claire L. Gorrie ◽  
Louise M. Judd ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Population Genomics ◽  
Bacterial Species ◽  
Critical Role ◽  
Mobile Element ◽  
Mobile Genetic Elements ◽  
Virulence Determinants ◽  
Genome Sequences ◽  
Genetic Elements ◽  
Resistant Strains

ABSTRACTMobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria’s ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in opportunistic pathogenKlebsiella pneumoniae, which are a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants inK. pneumoniaeinclude the polyketide synthesis lociybtandclb(also known aspks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin respectively. These loci are located within an MGE called ICEKp, which is the most common virulence-associated MGE ofK. pneumoniae,providing a mechanism for these virulence factors to spread within the population.Here we apply population genomics to investigate the prevalence, evolution and mobility ofybtandclbinK. pneumoniaepopulations through comparative analysis of 2,498 whole genome sequences. Theybtlocus was detected in 40% ofK. pneumoniaegenomes, particularly amongst those associated with invasive infections. We identified 17 distinctybtlineages and 3clblineages, each associated with one of 14 different structural variants of ICEKp. Comparison with the wider Enterobacteriaceae population showed occasional ICEKpacquisition by other members. Theclblocus was present in 14% of allK. pneumoniaeand 38.4% ofybt+ genomes. Hundreds of independent ICEKpintegration events were detected affecting hundreds of phylogenetically distinctK. pneumoniaelineages, including ≥19 in the globally-disseminated carbapenem-resistant clone CG258. A novel plasmid-encoded form ofybtwas also identified, representing a new mechanism forybtdispersal inK. pneumoniaepopulations. These data show that MGEs carryingybtandclbcirculate freely in theK. pneumoniaepopulation, including among multidrug-resistant strains, and should be considered a target for genomic surveillance along with AMR determinants.AUTHOR SUMMARYKlebsiella pneumoniaeinfections are becoming increasingly difficult to treat with antibiotics. SomeK. pneumoniaestrains also carry extra genes that allow them to synthesise yersiniabactin, an iron-scavenging molecule, which enhances their ability to cause disease. These genes are located on a genetic element that can easily transfer between strains. Here, we screened 2498K. pneumoniaegenome sequences and found substantial diversity in the yersiniabactin genes and the associated genetic elements, including a novel mechanism of transfer, and detected hundreds of distinct yersiniabactin acquisition events betweenK. pneumoniaestrains. We show that these yersiniabactin mobile genetic elements are specifically adapted to theK. pneumoniaepopulation but also occasionally acquired by other bacterial members belonging to the Enterobacteriaceae family such asE. coli.These insights into the movement and genetics of yersiniabactin genes allow tracking of the evolution and spread of yersiniabactin in globalK. pneumoniaepopulations and monitoring for acquisition of yersiniabactin in antibiotic-resistant strains.

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