Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci

Daptomycin (DAP) resistance in enterococci has been linked to mutations in genes that alter the cell envelope stress response (CESR) (liaFSR) and changes in enzymes that directly affect phospholipid homeostasis, and these changes may alter membrane composition, such as that of cardiolipin synthase (...

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Autores:
Davlieva, Milya
Zhang, Wanna
Arias, Cesar A.
Shamoo, Yousif
Tipo de recurso:
Article of journal
Fecha de publicación:
2013
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/3781
Acceso en línea:
http://hdl.handle.net/20.500.12495/3781
http://dx.doi.org/10.1128/AAC.01743-12
https://repositorio.unbosque.edu.co
Palabra clave:
Antibiotic
Antibacterial agent
Enterococcus
Resistance
Daptomycin
Rights
openAccess
License
Acceso abierto
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oai_identifier_str oai:repositorio.unbosque.edu.co:20.500.12495/3781
network_acronym_str UNBOSQUE2
network_name_str Repositorio U. El Bosque
repository_id_str
dc.title.spa.fl_str_mv Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
dc.title.translated.spa.fl_str_mv Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
title Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
spellingShingle Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
Antibiotic
Antibacterial agent
Enterococcus
Resistance
Daptomycin
title_short Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
title_full Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
title_fullStr Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
title_full_unstemmed Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
title_sort Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci
dc.creator.fl_str_mv Davlieva, Milya
Zhang, Wanna
Arias, Cesar A.
Shamoo, Yousif
dc.contributor.author.none.fl_str_mv Davlieva, Milya
Zhang, Wanna
Arias, Cesar A.
Shamoo, Yousif
dc.subject.keywords.spa.fl_str_mv Antibiotic
Antibacterial agent
Enterococcus
Resistance
Daptomycin
topic Antibiotic
Antibacterial agent
Enterococcus
Resistance
Daptomycin
description Daptomycin (DAP) resistance in enterococci has been linked to mutations in genes that alter the cell envelope stress response (CESR) (liaFSR) and changes in enzymes that directly affect phospholipid homeostasis, and these changes may alter membrane composition, such as that of cardiolipin synthase (Cls). While Cls substitutions are observed in response to DAP therapy, the effect of these mutations on Cls activity remains obscure. We have expressed, purified, and characterized Cls enzymes from both Enterococcus faecium S447 (residues 52 to 482; Cls447a) and Enterococcus faecalis S613 (residues 53 to 483; Cls613a) as well as Cls variants harboring a single-amino-acid change derived from DAP-resistant isolates of E. faecium. E. faecium Cls447a and E. faecalis Cls613a are tightly associated with the membrane and copurify with their substrate, phosphatidylglycerol (PG), and product, cardiolipin (CL). The amount of PG that copurifies with Cls is in molar excess to protein, suggesting that the enzyme localizes to PG-rich membrane regions. Both Cls447aH215R and Cls447aR218Q showed an increase in Vmax (μM CL/min/μM protein) from 0.16 ± 0.01 to 0.26 ± 0.02 and 0.26 ± 0.04, respectively, indicating that mutations associated with adaptation to DAP increase Cls activity. Modeling of Cls447a to Streptomyces sp. phospholipase D indicates that the adaptive mutations Cls447aH215R and Cls447aR218Q are proximal to the phospholipase domain 1 (PLD1) active site and near the putative nucleophile H217. As mutations to Cls are part of a larger genomic adaptation process, increased Cls activity is likely to be highly epistatic with other changes to facilitate DAP resistance.
publishDate 2013
dc.date.issued.none.fl_str_mv 2013
dc.date.accessioned.none.fl_str_mv 2020-08-13T19:15:47Z
dc.date.available.none.fl_str_mv 2020-08-13T19:15:47Z
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dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.local.none.fl_str_mv Artículo de revista
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dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.issn.none.fl_str_mv 1098-6596
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/3781
dc.identifier.doi.none.fl_str_mv http://dx.doi.org/10.1128/AAC.01743-12
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
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identifier_str_mv 1098-6596
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
url http://hdl.handle.net/20.500.12495/3781
http://dx.doi.org/10.1128/AAC.01743-12
https://repositorio.unbosque.edu.co
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Antimicrobial Agents and Chemotherapy, 1098-6596, Vol. 57, Nro. 1, 2013, p. 289 –296
dc.relation.uri.none.fl_str_mv https://aac.asm.org/content/57/1/289
dc.rights.local.spa.fl_str_mv Acceso abierto
dc.rights.accessrights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
info:eu-repo/semantics/openAccess
Acceso abierto
dc.rights.creativecommons.none.fl_str_mv 2012-10-31
rights_invalid_str_mv Acceso abierto
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2012-10-31
eu_rights_str_mv openAccess
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv American Society for Microbiology
dc.publisher.journal.spa.fl_str_mv Antimicrobial Agents and Chemotherapy
institution Universidad El Bosque
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spelling Davlieva, MilyaZhang, WannaArias, Cesar A.Shamoo, Yousif2020-08-13T19:15:47Z2020-08-13T19:15:47Z20131098-6596http://hdl.handle.net/20.500.12495/3781http://dx.doi.org/10.1128/AAC.01743-12instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquehttps://repositorio.unbosque.edu.coapplication/pdfengAmerican Society for MicrobiologyAntimicrobial Agents and ChemotherapyAntimicrobial Agents and Chemotherapy, 1098-6596, Vol. 57, Nro. 1, 2013, p. 289 –296https://aac.asm.org/content/57/1/289Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococciBiochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococciArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85AntibioticAntibacterial agentEnterococcusResistanceDaptomycinDaptomycin (DAP) resistance in enterococci has been linked to mutations in genes that alter the cell envelope stress response (CESR) (liaFSR) and changes in enzymes that directly affect phospholipid homeostasis, and these changes may alter membrane composition, such as that of cardiolipin synthase (Cls). While Cls substitutions are observed in response to DAP therapy, the effect of these mutations on Cls activity remains obscure. We have expressed, purified, and characterized Cls enzymes from both Enterococcus faecium S447 (residues 52 to 482; Cls447a) and Enterococcus faecalis S613 (residues 53 to 483; Cls613a) as well as Cls variants harboring a single-amino-acid change derived from DAP-resistant isolates of E. faecium. E. faecium Cls447a and E. faecalis Cls613a are tightly associated with the membrane and copurify with their substrate, phosphatidylglycerol (PG), and product, cardiolipin (CL). The amount of PG that copurifies with Cls is in molar excess to protein, suggesting that the enzyme localizes to PG-rich membrane regions. Both Cls447aH215R and Cls447aR218Q showed an increase in Vmax (μM CL/min/μM protein) from 0.16 ± 0.01 to 0.26 ± 0.02 and 0.26 ± 0.04, respectively, indicating that mutations associated with adaptation to DAP increase Cls activity. Modeling of Cls447a to Streptomyces sp. phospholipase D indicates that the adaptive mutations Cls447aH215R and Cls447aR218Q are proximal to the phospholipase domain 1 (PLD1) active site and near the putative nucleophile H217. As mutations to Cls are part of a larger genomic adaptation process, increased Cls activity is likely to be highly epistatic with other changes to facilitate DAP resistance.Acceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2012-10-31ORIGINALDavlieva, Milya.pdfDavlieva, Milya.pdfapplication/pdf1894158https://repositorio.unbosque.edu.co/bitstreams/186b90ef-9414-4814-8171-0b53a1203e78/download7bfa9212db91a15be991813ec6b62c93MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/c5e7eb4d-95f2-43aa-b3e8-9b97975386ba/download8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILDavlieva, Milya.pdf..jpgDavlieva, Milya.pdf..jpgimage/jpeg5775https://repositorio.unbosque.edu.co/bitstreams/5be647f9-02f2-4b5a-9310-982694573e46/download7210a811635d1799e7c05fee5d259be7MD53Davlieva, Milya.pdf.jpgDavlieva, Milya.pdf.jpgGenerated Thumbnailimage/jpeg6069https://repositorio.unbosque.edu.co/bitstreams/9657d043-9fcb-4ac5-81dc-eca3af25f80a/downloadc113334547e9084c7b4b013e517fc3e0MD55TEXTDavlieva, Milya.pdf.txtDavlieva, Milya.pdf.txtExtracted texttext/plain49875https://repositorio.unbosque.edu.co/bitstreams/3f9b1a2a-276a-4e55-a3b9-588e9f02991e/downloadf5fe061a09674fda03e7715e2e5d4aefMD5420.500.12495/3781oai:repositorio.unbosque.edu.co:20.500.12495/37812024-02-07 08:29:59.514restrictedhttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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