Molecule Information

General Information of the Molecule (ID: Mol01043)

• Name: Phosphatidylglycerol lysyltransferase (MPREF) ,Staphylococcus aureus
• Synonyms: Lysylphosphatidylglycerol synthase; LPG synthase; Multiple peptide resistance factor; fmtC
• Molecule Type: Protein
• Gene Name: mprF
• Sequence:
  MNQEVKNKIFSILKITFATALFIFVAITLYRELSGINFKDTLVEFSKINRMSLVLLFIGG
  GASLVILSMYDVILSRALKMDISLGKVLRVSYIINALNAIVGFGGFIGAGVRAMVYKNYT
  HDKKKLVHFISLILISMLTGLSLLSLLIVFHVFDASLILDKITWVRWVLYVVSFFLPLFI
  IYSMVRPPDKNNRFVGLYCTLVSCVEWLAAAVVLYFCGVIVDAHVSFMSFIAIFIIAALS
  GLVSFIPGGFGAFDLVVLLGFKTLGVPEEKVLLMLLLYRFAYYFVPVIIALILSSFEFGT
  SAKKYIEGSKYFIPAKDVTSFLMSYQKDIIAKIPSLSLAILVFFTSMIFFVNNLTIVYDA
  LYDGNHLTYYILLAIHTSACLLLLLNVVGIYKQSRRAIIFAMISILLITVATFFTYASYI
  LITWLAIIFVLLIVAFRRARRLKRPVRMRNIVAMLLFSLFILYVNHIFIAGTLYALDIYT
  IEMHTSVLRYYFWLTILIIAIIIGMIAWLFDYQFSKVRISSKIEDCEEIINQYGGNYLSH
  LIYSGDKQFFTNENKTAFLMYRYKASSLVVLGDPLGDENAFDELLEAFYNYAEYLGYDVI
  FYQVTDQHMPLYHNFGNQFFKLGEEAIIDLTQFSTSGKKRRGFRATLNKFDELNISFEII
  EPPFSTEFINELQHVSDLWLDNRQEMHFSVGEFNEEYLSKAPIGVMRNEENEVIAFCSLM
  PTYFNDAISVDLIRWLPELDLPLMDGLYLHMLLWSKEQGYTKFNMGMATLSNVGQLHYSY
  LRERLAGRVFEHFNGLYRFQGLRRYKSKYNPNWEPRFLVYRKDNSLWESLSKVMRVIRHK
• Function: Catalyzes the transfer of a lysyl group from L-lysyl-tRNA(Lys) to membrane-bound phosphatidylglycerol (PG), which produces lysylphosphatidylglycerol (LPG), a major component of the bacterial membrane with a positive net charge. LPG synthesis contributes to bacterial virulence as it is involved in the resistance mechanism against cationic antimicrobial peptides (CAMP) produces by the host's immune system (defensins, cathelicidins) and by the competing microorganisms (bacteriocins). In fact, the modification of anionic phosphatidylglycerol with positively charged L-lysine results in repulsion of the peptides. Consequently, MprF is shown to affect resistance and susceptibility to moenomycin and vancomycin, resistance to human defensins (HNP1-3) and evasion of oxygen-independent neutrophil killing and susceptibility to methicillin, oxacillin, bacitracin, gentamicin, beta-lactams and synthetic peptides (hBD3, CAP18) and other cationic antimicrobial peptides.
• Uniprot ID: MPRF_STAAU

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) 3 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: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: TLC and Western blotting analysis
• Experiment for Drug Resistance: Epsilometer test (E test) assay
• Mechanism Description: MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane.

Gentamicin

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: Gentamicin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: TLC and Western blotting analysis
• Experiment for Drug Resistance: Epsilometer test (E test) assay
• Mechanism Description: MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane.

Vancomycin

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: Vancomycin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: TLC and Western blotting analysis
• Experiment for Drug Resistance: Epsilometer test (E test) assay
• Mechanism Description: MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane.

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

Moenomycin

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: Moenomycin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: TLC and Western blotting analysis
• Experiment for Drug Resistance: Epsilometer test (E test) assay
• Mechanism Description: MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane.

References

• Ref 1: The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog. 2009 Nov;5(11):e1000660. doi: 10.1371/journal.ppat.1000660. Epub 2009 Nov 13.