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Mode of action of microbial bioactive metabolites

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Abstract

Pathogenic microorganisms can be suppressed by cell wall destruction. Biosynthesis of peptidoglycans forming bacterial cell wall is interrupted by glycopeptides which inhibit polymerization of a disaccharide formed byN-acetylglucosamine andN-acetylmuramic acid, β-lactams and their derivatives inhibit peptidoglycan cross-linking. Antibiotics inhibiting protein synthesis bind to different sites on the rRNA and interfere with the formation of the polypeptide chain. Tumor cells resistant to chemotherapeutic drugs overproduce proteins transporting the drugs out of cells; these proteins eliminate substances which inhibit transcription of transport proteins. Some antitumor drugs (anthracyclines, fluoroquinolones, acridinesetc.) act at topoisomerases which irreversibly bind to DNA and inhibit DNA synthesis. Immunosuppressants affect various components of the immune system such as T-helper, T-effector cell function, antigen presentation and B-cell function. Antiparasitics — avermectins — bind to a receptor of this Gab-gated chlorine channel in the nerve fiber of nematodes and anthropodes, increasing the permeability of the membrane for chloride ions; the increased transport of chloride ions into the cell causes the death of the parasite. Ionophores dissolve in phospholipid bilayers and enormously increase their ionic permeability. Respiration inhibitors block the transport of electrons at several places of the respiratory chain. Rifamycin binds to the β subunit of bacterial RNA polymerase, thereby blocking mRNA synthesis. Antiviral compounds inhibit the transcription of DNA by several mechanisms or by inhibition of viral entry into host cells.

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Abbreviations

Dap:

meso-2,6-diaminopimelic acid

Gab:

4-aminobutyric acid (Abu)

GleNAc:

N-acetylglucosamine

MDR:

multidrug resistance

MRP(1):

MDR protein (1)

MurNAc:

N-acetylmuramic acid

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  1. Institute of Microbiology, Academy of Sciences of the Czech Republic, 142 20, Prague, Czechia

    V. Běhal

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Correspondence to V. Běhal.

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This work was supported by theGrant Agency of the Academy of Sciences of the Czech Republic (grant no. S 502 0002).

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Běhal, V. Mode of action of microbial bioactive metabolites. Folia Microbiol 51, 359–369 (2006). https://doi.org/10.1007/BF02931577

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