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Literature summary for 2.3.2.3 extracted from

  • Ernst, C.M.; Slavetinsky, C.J.; Kuhn, S.; Hauser, J.N.; Nega, M.; Mishra, N.N.; Gekeler, C.; Bayer, A.S.; Peschel, A.
    Gain-of-function mutations in the phospholipid flippase MprF confer specific daptomycin resistance (2018), mBio, 9, e01659-18 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.2.3

Protein Variants

Protein Variants Comment Organism
I420N naturally occuring single nucleotide polymorphism (SNP) that does not alter daptomycin resistance and the lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus
L826F naturally occuring single nucleotide polymorphism (SNP) that does not alter daptomycin resistance and the lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus
P314L naturally occuring single nucleotide polymorphism (SNP) that does not alter daptomycin resistance, but slightly enhances the lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus
S295L naturally occuring single nucleotide polymorphism (SNP) that causes a slight daptomycin resistance and slightly enhances the lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus
S337L naturally occuring single nucleotide polymorphism (SNP) that does not alter daptomycin resistance and the lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus
T345A naturally occuring single nucleotide polymorphism (SNP) that can reproducibly cause strong, clinically relevant daptomycin resistance, the mutation leads to weakened intramolecular domain interactions of MprF, suggesting that daptomycin and friulimicin resistance-conferring mutations may alter the substrate range of the MprF flippase to directly translocate these lipopeptide antibiotics or other membrane components with crucial roles in the activity of these antimicrobials. MprF point mutation T345A causes cross-resistance only to daptomycin and the related lipopeptide antibiotic friulimicin B Staphylococcus aureus
V351E naturally occuring single nucleotide polymorphism (SNP) that causes a strong, clinically relevant daptomycin resistance and slightly reduced lysyl-phosphatidylglycerol synthesizing activity Staphylococcus aureus

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface
-
 Staphylococcus aureus 9986
-
cytoplasmic membrane
-
 Staphylococcus aureus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-lysyl-tRNALys + phosphatidylglycerol Staphylococcus aureus
-
 tRNALys + 3-O-L-lysyl-1-O-phosphatidylglycerol
-
 ?

Organism

Organism UniProt Comment Textmining
Staphylococcus aureus
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-lysyl-tRNALys + phosphatidylglycerol
-
 Staphylococcus aureus tRNALys + 3-O-L-lysyl-1-O-phosphatidylglycerol
-
 ?

Synonyms

Synonyms Comment Organism
MprF
-
 Staphylococcus aureus
MprF flippase
-
 Staphylococcus aureus
phospholipid flippase
-
 Staphylococcus aureus

General Information

General Information Comment Organism
malfunction gain-of-function mutations in the phospholipid flippase MprF confer specific daptomycin resistance, although the T345A mutation does not alter lysyl-phosphatidylglycerol (LysPG) synthesis, LysPG translocation, or the Staphylococcus aureus cell surface charge. MprF-mediated DAP-resistance relies on a functional flippase domain and is restricted to daptomycin and a related cyclic lipopeptide antibiotic, friulimicin B. Daptomycin-resistant (DAP-R) Staphylococcus aureus mutants emerge during therapy, featuring isolates which in most cases possess point mutations in the mprF gene. T345A is a naturally occuring single nucleotide polymorphism (SNP) that can reproducibly cause daptomycin resistance, the mutation leads to weakened intramolecular domain interactions of MprF, suggesting that daptomycin and friulimicin resistance-conferring mutations may alter the substrate range of the MprF flippase to directly translocate these lipopeptide antibiotics or other membrane components with crucial roles in the activity of these antimicrobials Staphylococcus aureus
physiological function enzyme MprF is a bifunctional bacterial resistance protein that synthesizes the positively charged lipid lysyl-phosphatidylglycerol (LysPG) and translocates it subsequently from the inner membrane leaflet to the outer membrane leaflet. MprF links lysine to negatively charged phosphatidylglycerol (PG) and translocates the resulting positively charged lysyl-PG (LysPG) to the outer leaflet of the cytoplasmic membrane (CM), resulting in electrostatic repulsion of cationic antimicrobial peptides (CAMPs), including human defensins and bacterial lantibiotics Staphylococcus aureus