The knowledge of the mode of action (MOA) is crucial for discovering new antibacterial drugs. The MOA of antibiotics explains how antibiotics can attack bacteria without affecting human cells. Creative Biolabs has developed a top drug discovery platform to determine the mode of action of antibacterial drugs in cell wall synthesis.
Bacterial cells are different from animal cells as they have cell walls. Therefore, a drug that attacks cell walls will have no significant negative effect on the cells of the mammalian host. The cell wall is composed of units of peptides (proteins) and glycans (sugars). Most bacteria have cell walls consisting of single or more protective layers on top of their cytoplasmic membranes. Gram-negative bacteria also have an additional outer lipid bilayer. Cell wall protects bacteria from injury. Inhibit cell wall synthesis is one of the most common modes of action for antibiotics. By inhibiting peptidoglycan synthesis, the growth of bacteria is prevented. These bacteria will be subjected to osmotic lysis.
Figure 1. Cell wall structures of Gram-positive and Gram-negative bacteria
Generally, the modes of actions of antibiotics for interference with cell wall are the following:
Interference with Peptidoglycan
Peptidoglycan is a promising target in bacterial cell wall for broad-spectrum antibacterial drug discovery, as the disaccharide-pentapeptide peptidoglycan structure is common to both Gram-negative and Gram-positive bacteria. Many antibiotics have effects on different stages of peptidoglycan, either synthesis or transport of its metabolic precursors or by direct action on its structural organization. For instance, beta-lactams Inhibit synthesis of peptidoglycan; vancomycin disrupts peptidoglycan cross-linkage; bacitracin disrupts the movement of peptidoglycan precursors. Knowing the mode of action of new antibiotics, we may also have some knowledge of mechanisms of resistance.
Interference with Teichoic Acids (TA)
Except for peptidoglycan, Gram-positive bacteria are comprised of a second, equally abundant component: teichoic acid. Teichoic acid is comprised of linear, polyol phosphate polymers that exist in one of two forms: wall teichoic acid (WTA) attached to wall peptidoglycan, and lipoteichoic acid (LTA) linked to membrane lipids. WTA are involved in many aspects of cell division and are essential for maintaining cell shape in rod-shaped organisms. LTA plays an important role in bacterial growth and physiology and contributes to membrane homeostasis. Both WTA and LTA are potential targets for new therapeutics to overcome bacterial infections.
Interference with Lipopolysaccharides (LPS)
Lipopolysaccharides (LPS) (also lipoglycans or endotoxins) are a kind of large molecules consisting of a lipid and a polysaccharide. They are important components in the outer membrane of Gram-negative bacteria and can act as antigens that elicit strong immune responses in animals. Both LPS synthesis and LPS transport are of crucial importance to Gram-negative bacteria. Interference of LPS is also an important MOA for antibiotics.
Creative Biolabs is a trusted partner in identifying the mode of action for novel antibiotics. For more detailed information, please feel free to contact us or directly sent us an inquiry.
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