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Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi

OBJECTIVES: This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use. METHODS: We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP...

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Autores principales: Cornick, Jennifer E., Harris, Simon R., Parry, Christopher M., Moore, Michael J., Jassi, Chikondi, Kamng'ona, Arox, Kulohoma, Benard, Heyderman, Robert S., Bentley, Stephen D., Everett, Dean B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886935/
https://www.ncbi.nlm.nih.gov/pubmed/24080503
http://dx.doi.org/10.1093/jac/dkt384
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author Cornick, Jennifer E.
Harris, Simon R.
Parry, Christopher M.
Moore, Michael J.
Jassi, Chikondi
Kamng'ona, Arox
Kulohoma, Benard
Heyderman, Robert S.
Bentley, Stephen D.
Everett, Dean B.
author_facet Cornick, Jennifer E.
Harris, Simon R.
Parry, Christopher M.
Moore, Michael J.
Jassi, Chikondi
Kamng'ona, Arox
Kulohoma, Benard
Heyderman, Robert S.
Bentley, Stephen D.
Everett, Dean B.
author_sort Cornick, Jennifer E.
collection PubMed
description OBJECTIVES: This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use. METHODS: We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002–08). RESULTS: Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143). Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into three genotypic groups based on dihydrofolate reductase (encoded by folA) mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a residue 92 substitution (56%) and those with a novel uncharacterized resistance genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP remained stable from 2004 onwards. CONCLUSIONS: S. pneumoniae exhibit almost universal co-trimoxazole resistance in vitro and in silico that we believe is driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance. Resistance has now reached a point of stabilizing evolution. The use of co-trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan Africa should be re-evaluated.
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spelling pubmed-38869352014-01-10 Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi Cornick, Jennifer E. Harris, Simon R. Parry, Christopher M. Moore, Michael J. Jassi, Chikondi Kamng'ona, Arox Kulohoma, Benard Heyderman, Robert S. Bentley, Stephen D. Everett, Dean B. J Antimicrob Chemother Original Research OBJECTIVES: This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use. METHODS: We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002–08). RESULTS: Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143). Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into three genotypic groups based on dihydrofolate reductase (encoded by folA) mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a residue 92 substitution (56%) and those with a novel uncharacterized resistance genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP remained stable from 2004 onwards. CONCLUSIONS: S. pneumoniae exhibit almost universal co-trimoxazole resistance in vitro and in silico that we believe is driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance. Resistance has now reached a point of stabilizing evolution. The use of co-trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan Africa should be re-evaluated. Oxford University Press 2014-02 2013-09-29 /pmc/articles/PMC3886935/ /pubmed/24080503 http://dx.doi.org/10.1093/jac/dkt384 Text en © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
spellingShingle Original Research
Cornick, Jennifer E.
Harris, Simon R.
Parry, Christopher M.
Moore, Michael J.
Jassi, Chikondi
Kamng'ona, Arox
Kulohoma, Benard
Heyderman, Robert S.
Bentley, Stephen D.
Everett, Dean B.
Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title_full Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title_fullStr Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title_full_unstemmed Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title_short Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi
title_sort genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst streptococcus pneumoniae in malawi
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886935/
https://www.ncbi.nlm.nih.gov/pubmed/24080503
http://dx.doi.org/10.1093/jac/dkt384
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