Chloramphenicol resistance in Pseudomonas aeruginosa is due to:
Bacteria have evolved in various ways to counter the toxic propeies of antimicrobial agents. These are the following: i. Inactivation of the antimicrobial drug Resistance to penicillin and cephalosporin antibiotics in many bacteria is due to production of an enzyme beta-lactamase, which inactivates the antimicrobial agent. Genes encoding betalactamases may be present on chromosome or plasmid. These genes may be constitutively expressed or induced by a beta-lactam antibiotic. Such form of resistance is seen in S.aureus, H.influenzae, E.coli, K.pneumoniae etc. Aminoglycoside modifying enzymes destroy the drug by adenylylating, phosphorylating, or acetylating them. The genes encoding for aminoglycoside modifying enzymes are usually found on plasmids and transposons. This type of resistance is seen in members of Enterobacteriaceae, Acinetobactersps, Pseudomonas aeruginosa, S.aureus, Campylobacterjejuni etc. ii. Alteration of the antimicrobial target As a result of mutation, the targets of the antimicrobial agents get lost or altered. Sometimes, the existing target may be replaced by an entirely novel protein. Resistances to penicillins/cephalosporins in MRSA, S. pneumoniae or enterococci are often to due to production of altered/novel penicillin binding proteins. Methylation of 23S ribosomal RNA renders the receptor on 50S subunit altered, thereby preventing the binding of erythromycin. Mutations in the 30S subunit of the ribosome interfere with ribosomal binding of streptomycin. Methylation of a single adenine in the bacterial 50s ribosome can lead to resistance against macrolides, lincosamides, and streptogramin B in S. aureus and S. pneumoniae. iii. Adaptation of alternative metabolic pathway Some sulfonamide-resistant bacteria do not require extracellular PABA but, like mammalian cells, can utilize preformed folic acid. A mutational loss in bacteria make them dependent on an external supply of thymine, which contributes to trimethoprim resistance. A mutational change in H. influenzae results in overproduction of dihydrofolate reductases, leading to trimethoprim resistance. iv. Active efflux pumping out of the drug Mutations in ceain bacteria permit the over-expression of the efflux-pump protein.Sometimes, an amino acid substitution in the efflux-pump protein makes it more efficient at expo of the drug. In either case, the intracellular antibiotic concentration is decreased and the bacterium becomes less susceptible to that antibiotic. This kind of resistance is seen to chloramphenicol (P.aeruginosa, K. pneumoniae, E. coli, S. typhimurium, V. cholerae), macrolides (Streptococcus pneumoniae, Enterococcus sps, Bacteroides sps, Pseudomonas sps and Enterobacteriaceae members), tetracyclines (S. aureus, E. coli, A. baumannii, S. typhimurium), aminoglycosides (E. coli, P.aeruginosa, A. baumannii) and beta-lactams (H. influenzae, P.aeruginosa, A. baumannii). v. Decreased permeability of the drug Some strains of P. aeruginosa and other gram-negative bacilli exhibit aminoglycoside resistance due to a transpo defect or membrane impermeabilization. Resistance to cefoxitin in E. coli and K. pneumoniae is due to mutations leading to narrowed outer membrane proteins. Ref: Colour Atlas and Textbook of diagnostic Microbiology by Elmer. W. Koneman; 5th edition.
Inactivation of the antimicrobial drug
Alteration of the antimicrobial target
Active efflux pumping out of the drug
Decreased permeability of the drug