Emergence of a multidrug resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13

Background Pneumococcal Conjugate Vaccine (PCV) which targets up to 13 serotypes of Streptococcus pneumoniae is very effective at reducing disease in young children; however, rapid increases in replacement with non-PCV serotypes remains a concern. Serotype 24F is one of the major invasive serotypes that mediates serotype replacement in France and multiple other countries. We aimed to identify the major pneumococcal lineage that has driven the increase of serotype 24F in France, and provide context for the findings by investigating the global diversity of serotype 24F pneumococci and characterise the driver lineage from a global perspective and elucidate its spatiotemporal transmission in France and across the world. Methods We whole-genome sequenced a collection of 419 serotype 24F S. pneumoniae from asymptomatic carriers and invasive disease cases among individuals <18 years old in France between 2003 and 2018. Genomes were clustered into Global Pneumococcal Sequence Clusters (GPSCs) and clonal complexes (CCs) so as to identify the lineages that drove the increase in serotype 24F in France. For each serotype 24F lineage, we evaluated the invasive disease potential and propensity to cause meningitis by comparing the proportion of invasive disease cases with that of carriers. To provide a global context of serotype 24F and the driver lineage, we extracted relevant genomes and metadata from the Global Pneumococcal Sequencing (GPS) project database (n=25,590) and additionally sequenced a collection of 91 pneumococcal isolates belonging to the lineage that were responsible for the serotype 24F increase in Spain during the PCV introduction for comparison. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted to understand the mechanism underlying the global spread of serotype 24F, evolutionary history and long-range transmissions of the driver lineage. Findings A multidrug-resistant pneumococcal lineage GPSC10 (CC230) drove the serotype 24F increase in both carriage and invasive disease in France after PCV13 introduction. When compared with other serotype 24F lineages, it exhibited a 1.4-fold higher invasive disease potential and 1.6-fold higher propensity to cause meningitis. Globally, serotype 24F was widespread, largely due to clonal dissemination of GPSC10, GPSC16 (CC66) and GPSC206 (CC7701) rather than recent capsular switching. Among these lineages, only GPSC10 was multidrug-resistant. It expressed 17 serotypes, with only 6 included in PCV13 and none of the expected PCVs covered all serotypes expressed by this lineage. Global phylogeny of GPSC10 showed that all serotype 24F isolates except for one were clustered together, regardless of its country of origin. Long-range transmissions of GPSC10-24F from Europe to Israel, Morocco and India were detected. Spatiotemporal analysis revealed that it took ~5 years for GPSC10-24F to spread across French provinces. In Spain, we detected that the serotype 24F driver lineage GPSC10 underwent a rapid change of serotype composition from serotype 19A to 24F during the introduction of PCV13 (targets 19A but not 24F), indicating that pre-existence of serotype variants enabled GPSC10 to survive and expand under vaccine-selective pressure. Interpretation Our work further shows the utility of bacterial genome sequencing to better understand the pneumococcal lineages behind the serotype changes and reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. Funding Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.

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Population genetic structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in children in Argentina

Microbial Genomics ◽

10.1099/mgen.0.000636 ◽

2021 ◽

Vol 7 (9) ◽

Author(s):

Paula Gagetti ◽

Stephanie W. Lo ◽

Paulina A. Hawkins ◽

Rebecca A. Gladstone ◽

Mabel Regueira ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Type Species ◽

Invasive Disease ◽

Multidrug Resistant ◽

Childhood Immunization ◽

Content Type ◽

Sequencing Project ◽

Link Type ◽

Immunization Programme

Invasive disease caused by Streptococcus pneumoniae (IPD) is one of the leading causes of morbidity and mortality in young children worldwide. In Argentina, PCV13 was introduced into the childhood immunization programme nationwide in 2012 and PCV7 was available from 2000, but only in the private market. Since 1993 the National IPD Surveillance Programme, consisting of 150 hospitals, has conducted nationwide pneumococcal surveillance in Argentina in children under 6 years of age, as part of the SIREVA II-OPS network. A total of 1713 pneumococcal isolates characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, belonging to three study periods: pre-PCV7 era 1998–1999 (pre-PCV), before the introduction of PCV13 2010–2011 (PCV7) and after the introduction of PCV13 2012–2013 (PCV13), were available for inclusion. Fifty-four serotypes were identified in the entire collection and serotypes 14, 5 and 1 represented 50 % of the isolates. Resistance to penicillin was 34.9 %, cefotaxime 10.6 %, meropenem 4.9 %, cotrimoxazole 45 %, erythromycin 21.5 %, tetracycline 15.4 % and chloramphenicol 0.4 %. All the isolates were susceptible to levofloxacin, rifampin and vancomycin. Of 1713 isolates, 1061 (61.9 %) were non-susceptible to at least one antibiotic and 235(13.7 %) were multidrug resistant. A subset of 413 isolates was randomly selected and whole-genome sequenced as part of Global Pneumococcal Sequencing Project (GPS). The genome data was used to investigate the population structure of S. pneumoniae defining pneumococcal lineages using Global Pneumococcal Sequence Clusters (GPSCs), sequence types (STs) and clonal complexes (CCs), prevalent serotypes and their associated pneumococcal lineages and genomic inference of antimicrobial resistance. The collection showed a great diversity of strains. Among the 413 isolates, 73 known and 36 new STs were identified belonging to 38 CCs and 25 singletons, grouped into 52 GPSCs. Important changes were observed among vaccine types when pre-PCV and PCV13 periods were compared; a significant decrease in serotypes 14, 6B and 19F and a significant increase in 7F and 3. Among non-PCV13 types, serogroup 24 increased from 0 % in pre-PCV to 3.2 % in the PCV13 period. Our analysis showed that 66.1 % (273/413) of the isolates were predicted to be non-susceptible to at least one antibiotic and 11.9 % (49/413) were multidrug resistant. We found an agreement of 100 % when comparing the serotype determined by Quellung and WGS-based serotyping and 98.4 % of agreement in antimicrobial resistance. Continued surveillance of the pneumococcal population is needed to reveal the dynamics of pneumococcal isolates in Argentina in post-PCV13. This article contains data hosted by Microreact.

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Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis

Open Biology ◽

10.1098/rsob.150269 ◽

2016 ◽

Vol 6 (3) ◽

pp. 150269 ◽

Cited By ~ 17

Author(s):

Lucy J. Hathaway ◽

Denis Grandgirard ◽

Luca G. Valente ◽

Martin G. Täuber ◽

Stephen L. Leib

Keyword(s):

Streptococcus Pneumoniae ◽

Disease Severity ◽

Invasive Disease ◽

Pneumococcal Isolate ◽

Capsule Type ◽

Infant Rat ◽

Serotype Replacement ◽

Inflammatory Cytokine Response ◽

Polysaccharide Capsules ◽

Experimental Pneumococcal Meningitis

Streptococcus pneumoniae bacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement.

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Faculty Opinions recommendation of DiiA is a novel dimorphic cell wall protein of Streptococcus pneumoniae involved in invasive disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726307838.793522911 ◽

2016 ◽

Author(s):

Charles Feldman

Keyword(s):

Cell Wall ◽

Streptococcus Pneumoniae ◽

Invasive Disease ◽

Cell Wall Protein

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DiiA is a novel dimorphic cell wall protein of Streptococcus pneumoniae involved in invasive disease

Journal of Infection ◽

10.1016/j.jinf.2016.04.010 ◽

2016 ◽

Vol 73 (1) ◽

pp. 71-81 ◽

Cited By ~ 2

Author(s):

María S. Escolano-Martínez ◽

Arnau Domenech ◽

José Yuste ◽

María I. Cercenado ◽

Carmen Ardanuy ◽

...

Keyword(s):

Cell Wall ◽

Streptococcus Pneumoniae ◽

Invasive Disease ◽

Cell Wall Protein

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Multidrug-Resistant Nontyphoidal Salmonella Associated with Invasive Disease in an Immunocompetent Child

The Indian Journal of Pediatrics ◽

10.1007/s12098-021-03923-1 ◽

2021 ◽

Author(s):

Shaily Saraf ◽

Bikramjit Singh Jafra ◽

Pallab Ray ◽

Amit Rawat ◽

Sanjay Verma

Keyword(s):

Invasive Disease ◽

Multidrug Resistant ◽

Immunocompetent Child

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Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.4.1037-1042.2001 ◽

2001 ◽

Vol 45 (4) ◽

pp. 1037-1042 ◽

Cited By ~ 94

Author(s):

Daniel F. Sahm ◽

James A. Karlowsky ◽

Laurie J. Kelly ◽

Ian A. Critchley ◽

Mark E. Jones ◽

...

Keyword(s):

United States ◽

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

The United States ◽

Multidrug Resistant ◽

Fluoroquinolone Resistance ◽

Resistance Patterns ◽

Changing Patterns ◽

Resistance To Penicillin

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

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Characterization of Two Multidrug-Resistant IncA/C Plasmids from the 1960s by Using the MinION Sequencer Device

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01121-16 ◽

2016 ◽

Vol 60 (11) ◽

pp. 6780-6786 ◽

Cited By ~ 15

Author(s):

Mónika Szabó ◽

Tibor Nagy ◽

Tímea Wilk ◽

Tibor Farkas ◽

Anna Hegyi ◽

...

Keyword(s):

Antibiotic Resistance ◽

Bacterial Genome ◽

Multidrug Resistant ◽

Phenotypic Change ◽

Long Reads ◽

Loss Of Resistance ◽

Rapid Characterization ◽

Resistance Island ◽

The 1960S

ABSTRACTTwo A/C incompatibility group (IncA/C family) plasmids from the 1960s have been sequenced and classified into the A/C2type 1 group. R16a and IP40a contain novel antibiotic resistance islands and a complete GIsul2 genomic island not previously found in the family. In the 173.1-kb R16a, the 29.9-kb antibiotic resistance island (ARI) is located in a unique backbone position not utilized by ARIs. ARIR16aconsists of Tn1, Tn6020, and Tn6333, harboring the resistance genesblaTEM-1DandaphA1band amermodule, respectively; a truncated Tn5393copy; and a gene cluster with unknown function. Plasmid IP40a is 170.4 kb in size and contains a 5.6-kb ARI inserted into thekfrAgene. ARIIP40acarryingblaTEM-1DandaphA1bgenes is composed of Tn1with a Tn6023insertion. Additionally, IP40a harbors single IS2, IS186, and Tn1000insertions scattered in the backbone; an IS150copy in GIsul2; and a complete Tn6333carrying amermodule at the position of ARIR16a. Loss of resistance markers in R16a, IP40a, and R55 was observed during stability tests. Every phenotypic change proved to be the result of recombination events involving mobile elements. Intramolecular transposition of IS copies that generated IP40a derivatives lacking large parts of the backbone could account for the formation of other family members, too. The MinION platform proved to be a valuable tool in bacterial genome sequencing since it generates long reads that span repetitive elements and facilitates full-length plasmid or chromosome assembly. Nanopore technology enables rapid characterization of large, low-copy-number plasmids and their rearrangement products.

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Streptococcus pneumoniae carriage in school children

Medical alphabet ◽

10.33667/2078-5631-2021-30-57-60 ◽

2021 ◽

Vol 1 (30) ◽

pp. 57-60

Author(s):

I. N. Protasova ◽

N. V. Bakhareva ◽

N. A. Ilyenkova ◽

E. S. Sokolovskaya ◽

T. A. Elistratova ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Antimicrobial Resistance ◽

School Children ◽

Clonal Diversity ◽

Multidrug Resistant ◽

Clonal Structure ◽

Serotype Distribution ◽

Antibiotic Resistant ◽

Oropharyngeal Swab ◽

Resistant Strains

Purpose. To investigate the serotype distribution, clonal structure and antimicrobial resistance of pneumococci isolated from schoolchildren.Materials and methods. During the period from 2012 to 2018 we examined 498 healthy school children aged 6 to 17 years. Oropharyngeal swab was taken from each child for culture, after that all S. pneumoniae strains were genotyped for serotype and ST-type deduction (PCR and sequencing, respectively). Antimicrobial resistance was also determined.Results. Pneumococcal culture was positive in 10.6 % of children. S. pneumoniae isolates belonged to seven serogroups and seven serotypes. Serogroup 6 and serotype 19F strains (15.1% each), and serogroup 9 strains (13.2%) were the most prevalent. S. pneumoniae33FA/37 and 3 (9.4 and 5.7%), serogroups 15 and 18 (7.6 and 5.7%), and 10A serotype (3.8%) were determined at a lower frequency. 20 detected ST-types belonged to 14 clonal complexes (CCs); CC156, CC447, and CC320 were predominant. 1.9% of isolates were penicillin-resistant; 13.2% – macrolide-, clindamycin-, and tetracycline-resistant. S. pneumoniae antibiotic resistant strains belonged to multidrug-resistant CCs 320, 315, and 156.Conclusion. S. pneumoniae prevalence in school children is not high. Pneumococcal population is characterized by serotype and clonal diversity including ‘invasive’ serotypes and genotypes. Most of strains are susceptible to antimicrobials.

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