Dr. Najlaa Al_shami
Antibiotics resistance is one of the biggest threats to global health.
It can occurs naturally, but misuse of antibiotics in humans & animals is accelerating the process.
Antibiotics resistance leads to higher medicals costs and increased mortality.
We need to understand the mechanisms of antibiotic resistance because a better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics and minimizing the emergence of antibiotic resistance.
There are many mechanisms that bacteria exhibit to protect themselves from antibiotics as the following:
1-Antibiotics modification; this occurs by synthesizing enzymes that destroy antibiotic molecules.
Synthesis of a bacterial enzyme, beta-lactamase is the major example of such mechanism of resistance.
This enzyme cleaves the beta-lactam ring by hydrolysis of the cyclic amide bond in beta-lactam ring. Among Gram negative bacilli, betalactamases are the most common mechanism of resistance.
2- Prevention of the entry of the antibiotics to the bacterial cell or pumping them out : This is based on the course of penetration of antibiotic throughout the outer membrane in the bacterial cell.
In Gram positive bacteria, penetration occurs by passive diffusion, while in Gram negative bacteria, protein channels (porins) are the site of entry of antibiotics.
Decrease in the outer membrane permeability cause pumping the antibiotic out faster than they can flow.
Also, alteration of the (porins) affacts drug penetration.
The resistance of P. aerugoinosa aganist aminoglycosides & fluoroquinolons is a typical example of such mechanism of resistance.
3- Alterations in the primary site of action: The antibiotics penetrate the cell, reach the target site but can't inhibit the a c t i v i t y of the target due to structural changes in the molecule. The resistance to penicillin among pneumococci is a clear example of such mechanism of resistance which
involves alteration in one or more of penicillin- binding proteins (PBP) .
4- Production of an alternative target (usually an enzyme).
This target is usually synthesized by bacteria to counter effect of antibiotic. The best known example of this mechanism of resistance is the production of alternative penicillin binding protein (PBP2a) by methicillin resistance staphylococcus aureus (MRSA).
References :
1- Gordon, Steven M. Antimicrobial resistance: An ecological approach to a growing threat. Modern Medicine 1998;36 (6): 376-9.
2- Hugo and Russel. Pharmaceutical Microbiology. 6th. ed. London: Black well science;1998: 91.
3- Jacobs, Christine. Life in Balance: cell wall and antibiotic resistance. Science 1997; 278 (5344): 1731- 1732.
4- www.who. int. mediacentre, fact sheet. November 2017. Antibiotic resistance. Mechanisms of antibiotics resistance
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