Cell wall-targeted antimicrobial therapy is a highly advanced and strategic approach in combating infectious diseases caused by bacteria and fungi. At Protheragen, we specialize in providing comprehensive preclinical development services that are meticulously tailored to support cell wall-targeted antimicrobial therapies.
Overview of Cell Wall-targeted Antimicrobial Therapy
Cell wall-targeted antimicrobial therapy is a groundbreaking strategy in the battle against microbial infections, especially as antibiotic resistance continues to rise. The bacterial cell wall, a rigid and protective barrier that lies outside the cell membrane, is crucial for maintaining cell shape and integrity. This unique structure is exclusive to bacteria and fungi, rendering it a prime target for antimicrobial agents. By selectively targeting the cell wall, these therapies can compromise the structural integrity of microbial cells, resulting in cell lysis or growth inhibition, while sparing human cells from adverse effects.
Fig.1 A model illustrating cell wall structure and antifungal drugs targeting specific components of the cell wall. (Ibe C., et al., 2021)
Mechanism of Cell Wall-Targeted Antimicrobial Therapy
The cell wall of bacteria and fungi is composed of complex polysaccharides and proteins that are essential for cell viability and function. In bacteria, the primary component of the cell wall is peptidoglycan, a mesh-like structure composed of sugars and amino acids. Fungi, on the other hand, have a cell wall composed of chitin, β-glucans, and mannoproteins. Antimicrobial agents targeting the cell wall can interfere with the synthesis, remodeling, or degradation of these components, leading to cell wall instability and eventual cell death.
Inhibition of Cell Wall Synthesis
Antibiotics such as β-lactams (e.g., penicillin, cephalosporins) and glycopeptides (e.g., vancomycin) inhibit enzymes involved in the synthesis of peptidoglycan. β-lactams bind to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan strands. Glycopeptides interfere with the terminal stages of peptidoglycan synthesis. In fungi, echinocandins inhibit the synthesis of β-(1,3)-D-glucan, a key structural polysaccharide in the fungal cell wall.
Disruption of Cell Wall Integrity
Antimicrobial enzymes, such as endolysins and lysostaphins, are derived from bacteriophages and degrade specific components of the bacterial cell wall. This leads to cell lysis. These enzymes can be engineered for enhanced stability, specificity, and efficacy. They are promising candidates for combating drug-resistant pathogens. In fungi, enzymes like chitinases can degrade chitin, a major component of the fungal cell wall, disrupting its integrity.
Inhibition of Cell Wall Remodeling
Autolysins are bacterial enzymes involved in the remodeling of the cell wall during growth and division. Inhibitors of autolysins can prevent proper cell wall maintenance, leading to cell lysis. In fungi, compounds that inhibit chitin synthase can disrupt the synthesis of chitin, a major component of the fungal cell wall. Additionally, targeting enzymes involved in the breakdown and re-synthesis of cell wall components can impair the ability of bacteria and fungi to adapt to environmental changes and stress.
Development of Cell Wall-targeted Antimicrobial Therapy
The development of cell wall-targeted antimicrobial therapies is a dynamic and evolving field, driven by the urgent need to address the growing threat of antibiotic-resistant infections. Traditional antibiotics like penicillin and vancomycin remain in widespread use, but resistance is increasing, prompting the development of newer generations of β-lactams and glycopeptides. Research is also focused on identifying novel inhibitors of cell wall synthesis enzymes, such as new β-lactamase inhibitors and derivatives of existing antibiotics.
Table 1. Representative drugs targeting the cell wall in the therapeutic of infectious diseases.
| Drug |
Mechanism |
Indications |
Stage |
| Caspofungin, Micafungin, Anidulafungin |
Inhibit β (1-3)-glucan synthase, disrupting cell wall integrity |
Candidemia, Aspergillosis, Refractory fungal infections |
Approved |
| Nikkomycin Z, Polyoxin |
Inhibit chitin synthase, weakening the cell wall |
Coccidioidomycosis, Blastomycosis (limited clinical use) |
Approved |
| Ibrexafungerp |
Inhibits glucan synthase, targeting the fungal cell wall |
Investigational for various fungal infections |
Approved |
| E1210 |
Targets the glycosylphosphatidylinositol anchor of cell wall proteins, disrupting cell wall function |
Investigational for fungal infections |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we provide comprehensive preclinical development services tailored for cell wall-targeted antimicrobial therapies. Our team of seasoned scientists, equipped with state-of-the-art technologies and advanced platforms, is dedicated to expediting the discovery and optimization of innovative antimicrobial agents.
Workflow of Cell Wall-targeted Antimicrobial Therapy Development
Target Identification and Validation
Utilizing genomic, proteomic, and bioinformatic tools, we identify and validate new cell wall targets for antimicrobial development.
Therapeutic Development
- Bacterial Cell Wall-targeted Therapies: β-Lactams, Glycopeptides, Lipid II Inhibitors
- Fungal Cell Wall-targeted Therapies: Echinocandins, Chitin Synthase Inhibitors, GPI Anchor Biosynthesis Inhibitors, Adhesion Inhibitors.
Preclinical Research
We conduct rigorous in vitro and in vivo experiments to assess the antimicrobial activity, toxicity, and pharmacokinetic profile of candidate compounds.
Types of Cell Wall-targeted Antimicrobial Therapies
By Pathogen Types
By Molecule Types
By exploiting the unique and essential nature of cell walls in bacteria and fungi, researchers are developing novel agents with improved efficacy and reduced resistance potential. At Protheragen, we are committed to advancing this field through our comprehensive preclinical development services, accelerating the discovery and optimization of next-generation antimicrobial therapies. If you are interested in our services, please feel free to contact us.
References
- Ibe, Chibuike, and Carol A. Munro. "Fungal cell wall: An underexploited target for antifungal therapies." PLoS Pathogens 17.4 (2021): e1009470.
- Zhydzetski, Aliaksandr, et al. "Agents targeting the bacterial cell wall as tools to combat Gram-positive pathogens." Molecules 29.17 (2024): 4065.
- Ahmadipour, Sanaz, Robert A. Field, and Gavin J. Miller. "Prospects for anti-Candida therapy through targeting the cell wall: A mini-review." The Cell Surface 7 (2021): 100063.
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only and cannot be used to diagnose, treat or manage patients.
