Molecule Information

General Information of the Molecule (ID: Mol00847)

• Name: Beta-lactam-inducible penicillin-binding protein (MECA) ,Staphylococcus aureus
• Synonyms: mecA; ftsI_1; pbp; AS852_00205; BN1321_10005; BSZ10_12685; SAMEA70245418_00035; ZH16; PBP2'; PBP2a; EC 3.4.16.4; Penicillin-binding protein 2; Penicillin-binding protein 2 prime; Penicillin-binding protein MecA; EC 2.4.1.129; Penicillin-binding protein PBP2a
• Molecule Type: Protein
• Gene Name: mecA
• Sequence:
  MKKIKIVPLILIVVVVGFGIYFYASKDKEINNTIDAIEDKNFKQVYKDSSYISKSDNGEV
  EMTERPIKIYNSLGVKDINIQDRKIKKVSKNKKRVDAQYKIKTNYGNIDRNVQFNFVKED
  GMWKLDWDHSVIIPGMQKDQSIHIENLKSERGKILDRNNVELANTGTAYEIGIVPKNVSK
  KDYKAIAKELSISEDYIKQQMDQNWVQDDTFVPLKTVKKMDEYLRDFAKKFHLTTNETES
  RNYPLGKATSHLLGYVGPINSEELKQKEYKGYKDDAVIGKKGLEKLYDKKLQHEDGYRVT
  IVDDNSNTIAHTLIEKKKKDGKDIQLTIDAKVQKSIYNNMKNDYGSGTAIHPQTGELLAL
  VSTPSYDVYPFMYGMSNEEYNKLTEDKKEPLLNKFQITTSPGSTQKILTAMIGLNNKTLD
  DKTSYKIDGKGWQKDKSWGGYNVTRYEVVNGNIDLKQAIESSDNIFFARVALELGSKKFE
  KGMKKLGVGEDIPSDYPFYNAQISNKNLDNEILLADSGYGQGEILINPVQILSIYSALEN
  NGNINAPHLLKDTKNKVWKKNIISKENINLLTDGMQQVVNKTHKEDIYRSYANLIGKSGT
  AELKMKQGETGRQIGWFISYDKDNPNMMMAINVKDVQDKGMASYNAKISGKVYDELYENG
  NKKYDIDE
• Uniprot ID: Q6I7E7_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

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cefmetazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefmetazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain TG1; 562
• In Vitro Model: Staphylococcus aureus strain SA113; 1280
• In Vitro Model: Staphylococcus aureus strain kU201; 1280
• In Vitro Model: Staphylococcus aureus strain kU201E; 1280
• In Vitro Model: Staphylococcus aureus strain kU203; 1280
• In Vitro Model: Staphylococcus aureus strain Tk388E; 1280
• In Vitro Model: Staphylococcus aureus strain Tk784; 1280
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Expression and inducibility in staphylococcus aureus of the mecA Gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein.

Diclofenac

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Staphylococcus aureus infection [2]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Diclofenac
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: mecA/blaZ pathway; Activation; hsa01501
• In Vivo Model: Murine skin and soft tissue infection model; Mus musculus
• Experiment for Molecule Alteration: Gene expression analysis; Cellular ATP level assay; Ethidium bromide efflux inhibition assay
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: High-dose diclofenac can inhibit the growth of MRSA, and does not easily induce drug-resistant mutations after continuous passage. Low-doses diclofenac can resensitize bacteria to beta-lactams, which help to circumvent drug resistance and improve the antibacterial efficacy of conventional antibiotics. Diclofenac can reduce the expression of genes and proteins associated with beta-lactam resistance, low dose diclofenac can inhibit MRSA antibiotic resistance via the mecA/blaZ pathway and related biofilms in implants.

References

• Ref 1: Regulation of the expression of the Beta-lactam antibiotic-resistance determinants in methicillin-resistant Staphylococcus aureus (MRSA). Biochemistry. 2014 Mar 18;53(10):1548-50. doi: 10.1021/bi500074w. Epub 2014 Mar 3.
• Ref 2: Diclofenac Resensitizes Methicillin-Resistant Staphylococcus aureus to Beta-Lactams and Prevents Implant Infections .Adv Sci (Weinh). 2021 May 3;8(13):2100681. doi: 10.1002/advs.202100681. eCollection 2021 Jul. 10.1002/advs.202100681