Microbial and fungal enzymes and structural proteins

Microbial and fungal enzymes and structural proteins represent a broad category of therapeutic targets essential for the survival, replication, and structural integrity of pathogenic bacteria and fungi. These targets are exploited in antimicrobial therapy to achieve selective toxicity, focusing on pathways or structures absent or significantly different in human cells, such as the peptidoglycan cell wall in bacteria or the ergosterol-containing membrane in fungi (Nature Reviews Microbiology, 2017). Key examples include bacterial transpeptidases (PBPs), DNA gyrase, and fungal 1,3-beta-glucan synthase (PubMed, 2022). Drugs interacting with these targets, including various classes of antibiotics and antifungals, aim to treat infectious diseases by either killing the pathogen or inhibiting its growth. However, the clinical utility of targeting these proteins is increasingly challenged by the rapid evolution of antimicrobial resistance, which occurs through target site mutations, enzymatic degradation of drugs, or efflux mechanisms (WHO, 2021). This entry is considered 'incorrect' as a single target because it encompasses thousands of distinct proteins across diverse kingdoms of life rather than a specific molecular entity.

Other names

Pathogen-derived proteinsMicrobial drug targetsFungal drug targetsAntimicrobial targets

The mechanisms of action involve the inhibition of essential biochemical pathways: beta-lactams inhibit cell wall cross-linking by binding to penicillin-binding proteins (PBPs); fluoroquinolones inhibit DNA supercoiling by targeting DNA gyrase; azoles prevent fungal membrane formation by inhibiting lanosterol 14-alpha-demethylase (CYP51); and echinocandins disrupt fungal cell wall integrity by inhibiting 1,3-beta-D-glucan synthase (StatPearls, 2023; Journal of Fungi, 2021).