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PW144308

Pw144308 View Pathway
drug action

Valsartan Drug Metabolism Action Pathway

Homo sapiens
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Creator: Ray Kruger

Created On: October 07, 2023 at 13:21

Last Updated: October 07, 2023 at 13:21

PW146720

Pw146720 View Pathway
drug action

Vanadium Drug Metabolism Action Pathway

Homo sapiens
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Creator: Ray Kruger

Created On: October 07, 2023 at 18:52

Last Updated: October 07, 2023 at 18:52

PW127233

Pw127233 View Pathway
drug action

Vancomycin Action Pathway

Staphylococcus aureus
Vancomycin is a glycopeptide antibiotic used to treat severe but susceptible bacterial infections such as MRSA (methicillin-resistant Staphylococcus aureus) infections. Administered intravenously, vancomycin is indicated in adult and pediatric patients for the treatment of septicemia, infective endocarditis, skin and skin structure infections, bone infections, and lower respiratory tract infections. Administered orally, vancomycin is indicated in adult and pediatric patients for the treatment of Clostridium difficile-associated diarrhea and for enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains). The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix, which forms the major structural component of Gram-positive cell walls. Vancomycin forms hydrogen bonds with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides, preventing the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. Vancomycin may also alter bacterial-cell-membrane permeability and RNA synthesis. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
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Creator: Karxena Harford

Created On: November 16, 2022 at 23:08

Last Updated: November 16, 2022 at 23:08

PW144631

Pw144631 View Pathway
drug action

Vancomycin Drug Metabolism Action Pathway

Homo sapiens
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Creator: Ray Kruger

Created On: October 07, 2023 at 14:04

Last Updated: October 07, 2023 at 14:04

PW292441

Pw292441 View Pathway
drug action

Vancomycin resistance Action Pathway (VanA operon)

Staphylococcus aureus
The VanA-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanA operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 7 genes which can be divided into regulatory (vanR and vanS), resistance (vanH, vanA and vanX) and accessory genes (vanY and vanZ). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. The vanH gene encodes an e D-lactate dehydrogenase, which converts pyruvate to D-lactate, a precursor for the altered peptidoglycan precursor (to counteract the effects of vancomycin, which targets the peptidoglycan by binding to D-alanine-D-alanine terminus of the peptide chains, inhibiting cell wall synthesis). A D-Ala-D-Ala dipeptidase, encoded by the vanX gene, hydrolyzes D-Ala-D-Ala dipeptides thus preventing their integration into the peptidoglycan and subsequent peptidoglycan formation in the presence of vancomycin. vanA encodes a D-alanine D-alanine ligase which synthesizes the D-Ala-D-Lac dipeptide that replaces the normal D-Ala-D-Ala in the peptidoglycan precursor, thereby reducing vancomycin's binding affinity. Additionally, the accessory gene vanY, encodes a D,D-carboxypeptidase that, ensures that only D-Ala-D-Lac is used in cell wall synthesis by eliminating the terminal D-alanine residue from peptidoglycan precursors while VanZ confers teicoplanin resistance through an unknown mechanism.
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Creator: Julia Wakoli

Created On: August 12, 2024 at 14:55

Last Updated: August 12, 2024 at 14:55

PW292442

Pw292442 View Pathway
drug action

Vancomycin resistance Action Pathway (VanB operon)

Staphylococcus aureus
The VanB-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in the VanB operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 7 genes which can be divided into regulatory (vanR and vanS), resistance (vanH, vanB and vanX) and accessory genes (vanY and vanW). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. The vanH gene encodes an e D-lactate dehydrogenase, which converts pyruvate to D-lactate, a precursor for the altered peptidoglycan precursor (to counteract the effects of vancomycin, which targets the peptidoglycan by binding to D-alanine-D-alanine terminus of the peptide chains, inhibiting cell wall synthesis). A D-Ala-D-Ala dipeptidase, encoded by the vanX gene, hydrolyzes D-Ala-D-Ala dipeptides thus preventing their integration into the peptidoglycan and subsequent peptidoglycan formation in the presence of vancomycin. vanB encodes a D-alanine D-alanine ligase which synthesizes the D-Ala-D-Lac dipeptide that replaces the normal D-Ala-D-Ala in the peptidoglycan precursor, thereby reducing vancomycin's binding affinity. Additionally, the accessory gene vanY, encodes a D,D-carboxypeptidase that, ensures that only D-Ala-D-Lac is used in cell wall synthesis by eliminating the terminal D-alanine residue from peptidoglycan precursors while VanW whose function is unknown.
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Creator: Julia Wakoli

Created On: August 12, 2024 at 16:03

Last Updated: August 12, 2024 at 16:03

PW292443

Pw292443 View Pathway
drug action

Vancomycin resistance Action Pathway (VanC operon)

Enterococcus gallinarum
The VanC-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanC operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 5 genes which can be divided into regulatory (vanR and vanS) and resistance (vanC, vanT and vanXY). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. vanC gene encodes a D-Ala-D-Ser ligase, which synthesizes D-Ala-D-Ser (D-alanine-D-serine) dipeptides instead of the usual D-Ala-D-Ala in the peptidoglycan precursor, which has reduced affinity for vancomycin and is added to UDP-MurNAc-tripeptide.vanXY gene encodes a bifunctional D,D-dipeptidase and D,D-carboxypeptidase that hydrolyzes any remaining D-Ala-D-Ala dipeptides and removes D-alanine from peptidoglycan precursors (UDP-MurNAc-pentapeptide[d-Ala]), ensuring that only D-Ala-D-Ser is incorporated into the cell wall. Lastly, VanT encodes a serine racemase that is membrane-bound and supplies d-Ser for the synthesis pathway.
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Creator: Julia Wakoli

Created On: August 12, 2024 at 16:40

Last Updated: August 12, 2024 at 16:40

PW292444

Pw292444 View Pathway
drug action

Vancomycin resistance Action Pathway (VanD operon)

Enterococcus faecium
The VanD-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanD operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 5 genes which can be divided into regulatory (vanR and vanS), resistance (vanH, vanD and vanX) and accessory (vanY). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. vanD gene encodes a D-Ala-D-Lac ligase, synthesizing the D-Ala-D-Lac (D-alanine-D-lactate) dipeptide, replacing the typical D-Ala-D-Ala in the peptidoglycan precursor, which has reduced affinity for vancomycin and is added to UDP-MurNAc-tripeptide. vanX encodes a D,D-dipeptidase that hydrolyzes D-Ala-D-Ala dipeptides, ensuring that only D-Ala-D-Lac is available for incorporation into the peptidoglycan, and subsequent peptidoglycan formation even in the presence of vancomycin. The vanH gene encodes an e D-lactate dehydrogenase, which converts pyruvate to D-lactate, a precursor for the altered peptidoglycan precursor (to counteract the effects of vancomycin, which targets the peptidoglycan by binding to D-alanine-D-alanine terminus of the peptide chains, inhibiting cell wall synthesis). Lastly, the accessory gene vanY, encodes a D,D-carboxypeptidase that, ensures that only D-Ala-D-Lac is used in cell wall synthesis by eliminating the terminal D-alanine residue from peptidoglycan precursors
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Creator: Julia Wakoli

Created On: August 12, 2024 at 18:32

Last Updated: August 12, 2024 at 18:32

PW292445

Pw292445 View Pathway
drug action

Vancomycin resistance Action Pathway (VanE operon)

Enterococcus faecalis
The VanE-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanE operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 5 genes which can be divided into regulatory (vanR and vanS) and resistance (vanE, vanXY and vanT). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. The VanE gene encodes D-Ala-D-Lac ligase that synthesizes the D-Ala-D-Lac dipeptide, which replaces the normal D-Ala-D-Ala in the peptidoglycan precursor to which vancomycin has less affinity. vanXY gene encodes a bifunctional D,D-dipeptidase and D,D-carboxypeptidase that hydrolyzes any remaining D-Ala-D-Ala dipeptides and removes D-alanine from peptidoglycan precursors (UDP-MurNAc-pentapeptide[d-Ala]), ensuring that only D-Ala-D-Ser is incorporated into the cell wall. Lastly, VanT encodes a serine racemase that is membrane-bound and supplies d-Ser for the synthesis pathway.
BioPAX SVG SBGN SBML PWML All files (.zip)

Creator: Julia Wakoli

Created On: August 12, 2024 at 19:29

Last Updated: August 12, 2024 at 19:29

PW292446

Pw292446 View Pathway
drug action

Vancomycin resistance Action Pathway (vanG operon)

Enterococcus faecalis
The VanG-type vancomycin resistance pathway enables enterococcal bacteria to resist the action of the glycopeptide antibiotic vancomycin. This pathway involves a series of genes organized in an the VanG operon, which encodes enzymes and regulatory proteins that alter the bacterial cell wall, making it resistant to vancomycin. The operon is made up of 8 genes which can be divided into regulatory (vanU, vanR and vanS), resistance (vanG, vanT and vanXY) and accessory(vanY and vanW). The vanR gene is a response regulator that is part of a two-component regulatory system and activates transcription once phosphorylated by histidine kinase that is encoded by vanS, after detecting vancomycin. Similar to vanR, vanU encodes for a transcriptional activator though not the primary activator. vanG gene encodes a D-Ala-D-Ser ligase, which synthesizes D-Ala-D-Ser (D-alanine-D-serine) dipeptides instead of the usual D-Ala-D-Ala in the peptidoglycan precursor, which has reduced affinity for vancomycin and is added to UDP-MurNAc-tripeptide.vanXY gene encodes a bifunctional D,D-dipeptidase and D,D-carboxypeptidase that hydrolyzes any remaining D-Ala-D-Ala dipeptides and removes D-alanine from peptidoglycan precursors (UDP-MurNAc-pentapeptide[d-Ala]), ensuring that only D-Ala-D-Ser is incorporated into the cell wall. The accessory gene vanY, encodes a D,D-carboxypeptidase that, ensures that only D-Ala-D-Lac is used in cell wall synthesis by eliminating the terminal D-alanine residue from peptidoglycan precursorswhile vanW's function is unknown. Lastly, VanT encodes a serine racemase that is membrane-bound and supplies d-Ser for the synthesis pathway.
BioPAX SVG SBGN SBML PWML All files (.zip)

Creator: Julia Wakoli

Created On: August 12, 2024 at 20:32

Last Updated: August 12, 2024 at 20:32