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 (...
- 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:repositorio.unbosque.edu.co:20.500.12495/3781 |
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UNBOSQUE2 |
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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 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.local.none.fl_str_mv |
Artículo de revista |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
format |
http://purl.org/coar/resource_type/c_6501 |
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 |
dc.identifier.repourl.none.fl_str_mv |
https://repositorio.unbosque.edu.co |
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 http://purl.org/coar/access_right/c_abf2 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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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.comTk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo= |