Class of antibiotics | Mechanisms | Descriptions |
---|---|---|
Beta-lactam antibiotics Penicillin, Cephalosporin, Imepenam. | a) Enzyme destruction | Destruction of the beta-lactam ring of antibiotic molecule. |
b) Mutation of PBPs | Methicillin resistance is due to the modification at allosteric binding site of PBPs. | |
c) Down regulation of porins | Diminished the transportation of polar antibiotics into the bacterial cell. Pseudomonas aeruginosa, Klepsiela pneumonia resistant to imepenam | |
Aminoglycosides Streptomycin, Kanamycin, Gentamycin | a) Ribosomal mutation | Mutation of bacterial A site on 16s RNA of 30S ribosome (Mycobacterium resistance to Streptomycin) |
b) Destruction by aminoglycoside metabolizing enzyme (AME) | There are three major enzymes, AACs (AG N-N acyltransferase), ANTs (AG O – Nucleotidyl transferase, APHs (AG O – phosphotransferase). Among all, AACs are more common in Gram-negative bacteria. | |
c) Cell membrane modification | In case of OM modification, the cell membrane is modified by incorporation of positively charged 4-amino-4-deoxy-L-arabinose, which repulses the polycationic aminoglycoside. | |
d) Efflux pump | The efflux pump which decreases the intracellular concentration. | |
Fluoroquinolones Ciprofloxacin, Ofloxacin, Levofloxacin | a) Decreased drug update | It may be due to the alteration in OM and activation of efflux pump. Both are common in Gram-negative bacteria, but S. aureus shows drug resistance through an efflux mechanism alone. |
b) Altered target | The two enzymes, which bind with fluoroquinolones, undergo mutation viz., DNA gyrase (Gram-negative bacteria) and topoisomerase IV (Gram-positive bacteria). | |
c) Qnr protein mediated | Qnr protein is due to expression of mutation that protects the nucleic acid enzyme from binding to fluoroquinolones. | |
Glycopeptides Vancomycin | Mutation in cell wall precursor component by replacement of C-terminal D-alanine with D-lactate or D-serine | There are six types of resistance (Van A, Van B, Van C, Van D, Van E and Van G) among these ABDEG are acquired resistance whereas C is intrinsic. Van A and B are located at plasmid where the rest of them located in the chromosome. |
Macrolides/lincosamides Erythromycin, Oleondomycin | a) Target site modification by methylation (Streptococci) at 23s rRNA of 50S ribosome. | There are nearly 40 erm genes are found among them erm A, B, C, F is reported in pathogenic microbes like Streptococcus, Enterococcus and Bacteroids |
b) Efflux pumps | In Gram-negative bacteria, it is mediated by ABC (ATP-binding cassette transporter) and MFS (major facilitator super-family). In case of Gram-negative bacteria, it is mediated by chromosomally encoded pumps. | |
c) Drug inactivation of enzymes | The enzyme like esterase and phosphoesterase (Enterococci) destroys erythromycin, 14, 15 member macrolides. But these enzymes do not destroy lincosamides. | |
Sulphonamides Sulfomethoxazole Sulfodoxine Sulfodimidine | Mutation of DHPS enzyme (Dihydropteroate synthase) responsible for binding of sulphonamide. | Mediated by sul1 and sul2 genes, which are mediated by horizontal transfer (plasmid coded). Trimethoprim shows resistance via plasmid borne resistance. |
Tetracyclines Doxycycline, Minocycline, Glycylcycline | a) Tetracycline efflux pump (efflux or TET proteins) | Efflux resistant genes are mediated by plasmids. Gram-positive efflux is regulated by an attenuation mechanism whereas Gram-negative efflux is mediated by repressor that binds with tetracycline. |
b) Drug modification | Chemical modification tetracycline by a cytoplasmic protein in presence of NADPH and Oxygen. But still it is unclear. | |
c) Target mutation | Modification of 30S ribosome, which is responsible for the attachment of aminoacyl tRNA to RNA ribosome. | |
d) By specific ribosome protection protein (Tet (O), a translational GTPase) | There are nine ribosomal protection proteins reported that protect the ribosome from tetracyclines. This is mediated by both plasmid and self-transmissible chromosomal elements (Conjugative transposons). |