Molecule Information

General Information of the Molecule (ID: Mol00854)

• Name: Cardiolipin synthase (CLS) ,Enterococcus faecalis
• Synonyms: CL synthase; cls; CWC53_05265; GBM73_14260; SMVRE20_01891
• Molecule Type: Protein
• Gene Name: clsA
• Sequence:
  MKIIVDNFFTILLIMNILLSFIIVFRERKETAQTWAWLLVLMFIPVVGFILYIFLGRGIS
  KEKIFDLKIQGKIGKNLEIEEDKQALMRGLYPHPPTGQVDVKQLIYMLTVFESTLYTTKN
  EITLFTDGREKFDALIEDIKQAEDHIHFQYYIYRSDALGEEVRDALTEAARRGVKVRVLL
  DAWGSTQVSSSFFQNLKKAGGEIAFFFPLFVPYINPRINYRNHRKIVVIDGKIGYTGGFN
  VGNEYLGLVKKFGYWRDNHLRIYGEAVYILQNRFLMDWNSQHTKEVGYSPKFFPSIHSTG
  DIAVQIVTSGPDTEHEQIKMTYLKMISLAKREILIQTPYYIPDGSIHEALKLALLSGVKV
  HIQIPNKPDHLLVYWATYSFAAELIEYGARIETYENGFIHAKTMIIDGGIVSVGSANIDV
  RSFRLDFEVNTLIYDERMASRVRKAFFEDSKISTHLTKEMYENRGIIIKMKEGLARLISP
  LL
• Function: Catalyzes the reversible phosphatidyl group transfer from one phosphatidylglycerol molecule to another to form cardiolipin (CL) (diphosphatidylglycerol) and glycerol.
• Uniprot ID: A0A455TTM7_ENTFC

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Enterococcaceae
Genus: Enterococcus
Species: Enterococcus faecalis

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Daptomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bacterial infection [ICD-11: 1A00-1C4Z] [1], [2], [3]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.R218Q
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis S613; 699185
• In Vitro Model: Enterococcus faecium S447; 1134840
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Mol00855
• Mechanism Description: Mutations in genes encoding proteins associated with cell envelope homeostasis (yycFG and liaFSR) and phospholipid metabolism (cardiolipin synthase [cls] and cyclopropane fatty acid synthetase [cfa]) were investigated in daptomycin resistance derivatives.

Disease Class: Bacterial infection [ICD-11: 1A00-1C4Z] [1], [2], [3]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.R267H
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis S613; 699185
• In Vitro Model: Enterococcus faecium S447; 1134840
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Mol00855
• Mechanism Description: Mutations in genes encoding proteins associated with cell envelope homeostasis (yycFG and liaFSR) and phospholipid metabolism (cardiolipin synthase [cls] and cyclopropane fatty acid synthetase [cfa]) were investigated in daptomycin resistance derivatives.

Disease Class: Bacterial infection [ICD-11: 1A00-1C4Z] [1], [2], [3]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Daptomycin
• Molecule Alteration: Frameshift mutation; p.NFQ77-79del
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis S613; 699185
• In Vitro Model: Enterococcus faecium S447; 1134840
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Mol00855
• Mechanism Description: Mutations in genes encoding proteins associated with cell envelope homeostasis (yycFG and liaFSR) and phospholipid metabolism (cardiolipin synthase [cls] and cyclopropane fatty acid synthetase [cfa]) were investigated in daptomycin resistance derivatives.

References

• Ref 1: Biochemical characterization of cardiolipin synthase mutations associated with daptomycin resistance in enterococci. Antimicrob Agents Chemother. 2013 Jan;57(1):289-96. doi: 10.1128/AAC.01743-12. Epub 2012 Oct 31.
• Ref 2: Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression to resistance. Antimicrob Agents Chemother. 2013 Nov;57(11):5373-83. doi: 10.1128/AAC.01473-13. Epub 2013 Aug 19.
• Ref 3: Defining daptomycin resistance prevention exposures in vancomycin-resistant Enterococcus faecium and E. faecalis. Antimicrob Agents Chemother. 2014 Sep;58(9):5253-61. doi: 10.1128/AAC.00098-14. Epub 2014 Jun 23.