Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain

Jordi Càmara; Meritxell Cubero; Antonio J. Martín-Galiano; Ernesto García; Imma Grau; Jesper B. Nielsen; Peder Worning; Fe Tubau; Román Pallarés; M. Ángeles Domínguez; Mogens Kilian; Josefina Liñares; Henrik Westh; Carmen Ardanuy

doi:10.1093/jac/dky305

Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain

Jordi Càmara, Meritxell Cubero, Antonio J. Martín-Galiano, Ernesto García, Imma Grau, Jesper B. Nielsen, Peder Worning, Fe Tubau, Román Pallarés, M. Ángeles Domínguez, Mogens Kilian, Josefina Liñares, Henrik Westh, Carmen Ardanuy^*

^*Corresponding author for this work

Department of Clinical Medicine

7 Citations (Scopus)

Abstract

Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain ^9V -156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987–2016. Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing. Results: Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b–ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of b-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background. Conclusions: Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.

Original language	English
Journal	Journal of Antimicrobial Chemotherapy
Volume	73
Issue number	11
Pages (from-to)	2941-2951
ISSN	0305-7453
DOIs	https://doi.org/10.1093/jac/dky305
Publication status	Published - 1 Nov 2018

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Càmara, J., Cubero, M., Martín-Galiano, A. J., García, E., Grau, I., Nielsen, J. B., Worning, P., Tubau, F., Pallarés, R., Ángeles Domínguez, M., Kilian, M., Liñares, J., Westh, H., & Ardanuy, C. (2018). Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain. Journal of Antimicrobial Chemotherapy, 73(11), 2941-2951. https://doi.org/10.1093/jac/dky305

Càmara, J, Cubero, M, Martín-Galiano, AJ, García, E, Grau, I, Nielsen, JB, Worning, P, Tubau, F, Pallarés, R, Ángeles Domínguez, M, Kilian, M, Liñares, J, Westh, H & Ardanuy, C 2018, 'Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain', Journal of Antimicrobial Chemotherapy, vol. 73, no. 11, pp. 2941-2951. https://doi.org/10.1093/jac/dky305

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title = "Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain",

abstract = " Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain 9V -156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987–2016. Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing. Results: Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b–ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of b-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background. Conclusions: Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection. ",

author = "Jordi C{\`a}mara and Meritxell Cubero and Mart{\'i}n-Galiano, {Antonio J.} and Ernesto Garc{\'i}a and Imma Grau and Nielsen, {Jesper B.} and Peder Worning and Fe Tubau and Rom{\'a}n Pallar{\'e}s and {{\'A}ngeles Dom{\'i}nguez}, M. and Mogens Kilian and Josefina Li{\~n}ares and Henrik Westh and Carmen Ardanuy",

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doi = "10.1093/jac/dky305",

language = "English",

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T1 - Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain

AU - Càmara, Jordi

AU - Cubero, Meritxell

AU - Martín-Galiano, Antonio J.

AU - García, Ernesto

AU - Grau, Imma

AU - Nielsen, Jesper B.

AU - Worning, Peder

AU - Tubau, Fe

AU - Pallarés, Román

AU - Ángeles Domínguez, M.

AU - Kilian, Mogens

AU - Liñares, Josefina

AU - Westh, Henrik

AU - Ardanuy, Carmen

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain 9V -156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987–2016. Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing. Results: Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b–ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of b-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background. Conclusions: Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.

AB - Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain 9V -156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987–2016. Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing. Results: Two hundred and twenty-seven adult cases of IPD caused by PMEN3 were identified. PMEN3 caused mainly pneumonia (84%) and the 30 day mortality rate was 23.1%. Evidence of recombination events was found, mostly in three regions, namely the capsular operon (associated with capsular switching) and adjacent regions containing pbp2x and pbp1a, the murM gene and the pbp2b–ddl region. Some of these genetic changes generated successful new variant serotype lineages, including one of serotype 11A that is not included in the current PCV13 vaccine. Other genetic changes led to increased MICs of b-lactams. Notably, most isolates also harboured prophages coding for PblB-like proteins. Despite these adaptations, the ability of this clone to cause IPD remained unchanged over time, highlighting the importance of its core genetic background. Conclusions: Our study demonstrated successful adaptation of PMEN3 to persist over time despite the introduction of broader antibiotics and conjugate vaccines. In addition to enhancing understanding of the molecular evolution of PMEN3, these findings highlight the need for the development of non-serotype-based vaccines to fight pneumococcal infection.

U2 - 10.1093/jac/dky305

DO - 10.1093/jac/dky305

M3 - Journal article

C2 - 30165641

AN - SCOPUS:85055202103

SN - 0305-7453

VL - 73

SP - 2941

EP - 2951

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 11

ER -

Evolution of the b-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain

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