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Biology Articles » Microbiology » The challenge of antibiotic resistance: Need to contemplate » Mechanism of resistance

Mechanism of resistance
- The challenge of antibiotic resistance: Need to contemplate

The use of antibiotics should have created a catastrophic situation for microbial populations but the genetic flexibility allowed bacteria to survive and multiply under the antibiotic pressure.

Bacteria can resist antibiotics as a result of chromosomal mutation or by exchange of genetic materials, which carry resistance genes, through transformation, transduction or conjugation by plasmids8. The mechanism of resistance to antimicrobial agents can be due to9 (i) Impermeability of the drug: This is the most frequent cause of intrinsic resistance. Resistance in Enterococcus sp. and Pseudomonas aeruginosa is a good example of such mechanisms; (ii) alteration in target molecules—This is one of the most important mechanisms of resistance to clinically used antibacterial drugs, for example, methicillin resistant S. aureus with altered penicillin binding proteins; (iii) enzymatic drug modifications—b-lactamase enzymes currently account for most of the resistance to penicillins and cephalosporins. b-lactamases affect a common drug site i.e., b-lactam ring. Penicillins, cephalosporins, monobactams and carbapenems can all be hydrolyzed by multiple members of the beta lactamase family of enzymes, resulting in a microbiologically ineffective compound. The other important class of antibiotics, which are destroyed by enzymes are aminoglycosides due to the action of aminoglycoside - modifying enzymes produced by the bacteria; (iv) efflux—The role of efflux of drug from the bacterial cell as a resistance mechanism is comparatively less common in clinical practice. Although both chromosomal mutations or genetic transfer can be responsible for the resistance acquisition, it is the transferable resistance which poses a great threat as it can achieve much larger dimensions due to wide and rapid dissemination. This transferable resistance is carried on R plasmids. A single plasmid can carry a number of genes coding for multiple drug resistance10. It has been suggested earlier that evolution of multi drug resistant plasmids in pathogens is a comparatively recent phenomenon which came into existence after the introduction of antibiotics after 1940s. This further supports the observation that the use of antibiotic itself has been responsible for emergence of resistance in the pathogenic bacteria in clinical practice.

While plasmids act as vectors of resistance genes, the genes themselves are most often located on discrete movable DNA elements called transposons10. The important process in the gene pick up is done by transposons carrying multiple antibiotic resistance genes. Integron is the key structural constituent of a transposons11. Integron is a mobile DNA element with a specific structure consisting of two conserved segments flanking a central region - “cassette”. Genes encoding functions like resistance can be inserted in this region. These transposes carrying (R) genes have the ability to enter a conjugative plasmid or a chromosomes12.

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