A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae

Detalhes bibliográficos
Autor(a) principal: Aggarwal, Surya D.
Data de Publicação: 2021
Outros Autores: Lloyd, Adrian J., Yerneni, Saigopalakrishna S., Narciso, Ana Rita, Shepherd, Jennifer, Roper, David I., Dowson, Christopher G., Filipe, Sergio R., Hiller, N. Luisa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/123687
Resumo: Grant R00-DC-011322 LISBOA-01-0145-FEDER-016417 G0400848 G1100127 MR/N002679/1
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spelling A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniaeautolysiscell wallStreptococcus pneumoniaestringent responsetranslation quality controlGeneralGrant R00-DC-011322 LISBOA-01-0145-FEDER-016417 G0400848 G1100127 MR/N002679/1Survival in the human host requires bacteria to respond to unfavorable conditions. In the important Gram-positive pathogen Streptococcus pneumoniae, cell wall biosynthesis proteins MurM and MurN are tRNA-dependent amino acyl transferases which lead to the production of branched muropeptides. We demonstrate that wild-type cells experience optimal growth under mildly acidic stressed conditions, but ΔmurMN strain displays growth arrest and extensive lysis. Furthermore, these stress conditions compromise the efficiency with which alanyl-tRNAAla synthetase can avoid noncognate mischarging of tRNAAla with serine, which is toxic to cells. The observed growth defects are rescued by inhibition of the stringent response pathway or by overexpression of the editing domain of alanyl-tRNAAla synthetase that enables detoxification of tRNA misacylation. Furthermore, MurM can incorporate seryl groups from mischarged Seryl-tRNAAlaUGC into cell wall precursors with exquisite specificity. We conclude that MurM contributes to the fidelity of translation control and modulates the stress response by decreasing the pool of mischarged tRNAs. Finally, we show that enhanced lysis of ΔmurMN pneumococci is caused by LytA, and the murMN operon influences macrophage phagocytosis in a LytA-dependent manner. Thus, MurMN attenuates stress responses with consequences for host-pathogen interactions. Our data suggest a causal link between misaminoacylated tRNA accumulation and activation of the stringent response. In order to prevent potential corruption of translation, consumption of seryl-tRNAAla by MurM may represent a first line of defense. When this mechanism is overwhelmed or absent (ΔmurMN), the stringent response shuts down translation to avoid toxic generation of mistranslated/misfolded proteins.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitInstituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNAggarwal, Surya D.Lloyd, Adrian J.Yerneni, Saigopalakrishna S.Narciso, Ana RitaShepherd, JenniferRoper, David I.Dowson, Christopher G.Filipe, Sergio R.Hiller, N. Luisa2021-09-03T00:12:27Z2021-04-062021-04-06T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/123687eng0027-8424PURE: 29170041https://doi.org/10.1073/pnas.2018089118info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:05:02Zoai:run.unl.pt:10362/123687Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:08.806006Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
title A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
spellingShingle A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
Aggarwal, Surya D.
autolysis
cell wall
Streptococcus pneumoniae
stringent response
translation quality control
General
title_short A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
title_full A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
title_fullStr A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
title_full_unstemmed A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
title_sort A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae
author Aggarwal, Surya D.
author_facet Aggarwal, Surya D.
Lloyd, Adrian J.
Yerneni, Saigopalakrishna S.
Narciso, Ana Rita
Shepherd, Jennifer
Roper, David I.
Dowson, Christopher G.
Filipe, Sergio R.
Hiller, N. Luisa
author_role author
author2 Lloyd, Adrian J.
Yerneni, Saigopalakrishna S.
Narciso, Ana Rita
Shepherd, Jennifer
Roper, David I.
Dowson, Christopher G.
Filipe, Sergio R.
Hiller, N. Luisa
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv DCV - Departamento de Ciências da Vida
UCIBIO - Applied Molecular Biosciences Unit
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Aggarwal, Surya D.
Lloyd, Adrian J.
Yerneni, Saigopalakrishna S.
Narciso, Ana Rita
Shepherd, Jennifer
Roper, David I.
Dowson, Christopher G.
Filipe, Sergio R.
Hiller, N. Luisa
dc.subject.por.fl_str_mv autolysis
cell wall
Streptococcus pneumoniae
stringent response
translation quality control
General
topic autolysis
cell wall
Streptococcus pneumoniae
stringent response
translation quality control
General
description Grant R00-DC-011322 LISBOA-01-0145-FEDER-016417 G0400848 G1100127 MR/N002679/1
publishDate 2021
dc.date.none.fl_str_mv 2021-09-03T00:12:27Z
2021-04-06
2021-04-06T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/123687
url http://hdl.handle.net/10362/123687
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0027-8424
PURE: 29170041
https://doi.org/10.1073/pnas.2018089118
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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