Molecule Information

General Information of the Molecule (ID: Mol01044)

• Name: Phosphatidylglycerophosphate synthase (PGSA) ,Staphylococcus aureus
• Synonyms: Phosphatidylglycerophosphate synthase; PGP synthase; SAV1283
• Molecule Type: Protein
• Gene Name: pgsA
• Sequence:
  MNIPNQITVFRVVLIPVFILFALVDFGFGNVSFLGGYEIRIELLISGFIFILASLSDFVD
  GYLARKWNLVTNMGKFLDPLADKLLVASALIVLVQLGLTNSVVAIIIIAREFAVTGLRLL
  QIEQGFVSAAGQLGKIKTAVTMVAITWLLLGDPLATLIGLSLGQILLYIGVIFTILSGIE
  YFYKGRDVFKQK
• Function: This protein catalyzes the committed step to the synthesis of the acidic phospholipids.
• Uniprot ID: PGSA_STAAM

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Staphylococcaceae
Genus: Staphylococcus
Species: Staphylococcus aureus

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: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Disease Class: Complicated skin infection Staphylococcus aureus infection [1]

• Resistant Disease: Complicated skin infection Staphylococcus aureus infection [ICD-11: 1B21.1]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Disease Class: Complicated soft tissue infection [1]

• Resistant Disease: Complicated soft tissue infection [ICD-11: 1B7Y.0]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

Disease Class: Right-sided endocarditis [1]

• Resistant Disease: Right-sided endocarditis [ICD-11: BB41.0]
• Resistant Drug: Daptomycin
• Molecule Alteration: Missense mutation; p.V59D+p.A64V+p.K75N+p.Ins.G76;Q77+p.S177F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Staphylococcus aureus MRSA32 [A5948]; 553567
• In Vitro Model: Staphylococcus aureus RN6607 [A8115]; 553573
• In Vitro Model: Staphylococcus aureus RN9120 [A8117]; 553574
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutation in each of these genes act similarly to reduce the net-negative charge of the cell membrane leading to electrorepulsion of daptomycin. They may act in isolation or in concert with each other, particularly for mutations in mprF and cls2.

References

• Ref 1: Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus. PLoS One. 2012;7(1):e28316. doi: 10.1371/journal.pone.0028316. Epub 2012 Jan 6.