Mechanism of action of Penicillin on different types of bacteria

Mechanism of action of Penicillin on different types of bacteria

History:

The discovery of penicillin is attributed toScottishscientist and Nobel laureateAlexander Flemingin 1928.He showed that, ifPenicillium notatum were grown in the appropriate substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin. Thisserendipitousobservation began the modern era of antibiotic discovery. The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey together with the German Nobel laureate Ernst Chainand the English biochemistNorman Heatley.

Production:

Penicillin is a secondary metaboliteof fungus Penicilliumthat is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin.

-ketoglutarate + AcCoA homocitrate L--aminoadipic acid L-Lysine + -lactam

The by-product L-Lysine inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production.

The Penicillium cells are grown using a technique called fed-batchculture, in which the cells are constantly subject to stress and will produce plenty of penicillin. The carbon sources that are available are also important: Glucose inhibits penicillin, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must be controlled automatically.

Mechanism:

Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. -Lactam antibiotics work by inhibiting the formation of peptidoglycan cross-link in the bacterial cell wall. The -lactam moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the peptidoglycan molecules in bacteria. The enzymes that hydrolyze the peptidoglycan cross-links continue to function, which weakens the cell wall of the bacterium (in other words, the antibiotic causes cytolysis or death due to osmotic pressure). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the bacteria's existing peptidoglycan.

Gram-positive bacteria are called protoplasts when they lose their cell wall. Gram-negative bacteria do not lose their cell wall completely and are calledspheroplasts after treatment with penicillin.

Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing its disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for susceptible organisms.

Penicillins, like other -lactam antibiotics, block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, thephotosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of the evolution of plastid division in land plants.

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