Target intelligence / Profile preview

Cutibacterium acnes metabolic and cell wall enzymes

Molecular classification
Enzyme
01

Overview

Cutibacterium acnes metabolic and cell wall enzymes are a diverse group of proteins essential for the survival, structural integrity, and pathogenicity of the bacterium within the human skin environment [1, 3]. Cell wall enzymes, such as penicillin-binding proteins (PBPs) and Mur ligases, are responsible for the synthesis and maintenance of the peptidoglycan layer, which protects the bacterium from osmotic stress and is a primary target for beta-lactam antibiotics [1, 2]. Metabolic enzymes, including lipases (e.g., GehA), sialidases, and hyaluronidases, allow the bacterium to utilize sebum as a nutrient source and degrade host tissues, leading to the release of pro-inflammatory fatty acids and tissue damage [3, 4, 10]. Additionally, enzymes involved in fatty acid synthesis (e.g., KAS III) and DNA replication (e.g., DNA gyrase) are essential for bacterial proliferation and are targeted by quinolones and novel small-molecule inhibitors [5, 7, 8]. Targeting these enzymes is a cornerstone of acne therapy, aiming to reduce bacterial colonization and the subsequent inflammatory response while minimizing the impact on the beneficial skin microbiota [6, 9]. Recent research focuses on developing highly specific inhibitors and enzybiotics to overcome the rising challenge of antibiotic resistance [2, 8].

Other names
Propionibacterium acnes enzymesC. acnes cell wall enzymesC. acnes metabolic enzymesC. acnes virulence enzymes
02

Mechanism of action

Inhibition of peptidoglycan synthesis by binding to penicillin-binding proteins, inhibition of DNA replication by targeting DNA gyrase and topoisomerase IV, inhibition of folic acid synthesis via dihydropteroate synthase, inhibition of fatty acid synthesis via KAS III, and direct enzymatic degradation of the cell wall peptidoglycan.

03

Biological functions

Cell wall synthesisMetabolismLipid biosynthesisBiofilm formationPathogenesis
04

Disease associations

InfectionAcne vulgarisInflammation
05

Safety considerations

Development of antimicrobial resistance [1, 8]Disruption of the commensal skin microbiome [1, 6]Topical irritation and dryness [4]
06

Interacting drugs

Penicillin

7 more in the full profile.

07

Biomarkers

Cutibacterium acnes bacterial load [1, 7]Sebum free fatty acid levels [3, 4]C. acnes phylotype distribution (e.g., IA1, IA2) [2, 10]Pro-inflammatory cytokine levels (e.g., IL-1β, IL-8) [6, 10]

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