![]() ![]() S.Share on Pinterest WLADIMIR BULGAR/Getty Images PBP2a shows a high resistance to β-lactam antibiotics. ![]() mec A gene encodes PBP2a protein, a new penicillin-binding protein, that is required to change a native staphylococcal PBP. Similarly, in Staphylococcus aureus, the resistance to methicillin and oxacillin is associated with integration of a mobile genetic element – “staphylococcal cassette chromosome mec” – into the chromosome of S.aureus that contains resistance gene mec A. The resistance of Enterococcus faecium to ampicillin and Streptococcus pneumoniae to penicillin is by this mechanism. The presence of mutation in penicillin-binding protein leads to a reduced affinity to β-lactam antibiotics. In place of DNA gyrase or topoisomerase IV, mammalian cells possess topoisomerase II, which has very low affinity for FQ-hence low toxicity to cells.Īlteration in PBP: Modification of the PBP is a favored mechanism of resistance to Gram-positive bacteria, whereas production of β-lactamases is a mechanism for the development of resistance to Gram-negative bacteria. Greater affinity for this enzyme may confer higher potency against Gram-positive bacteria. In Gram-positive bacteria, the major target of action is topoisomerase IV which nicks and separate's daughter DNA strand after DNA replication. The FQ's bind to A subunit with high affinity and interfere with its strand cutting and resealing function. A subunit carries out the nicking of DNA, B subunit introduces negative supercoils, and then A subunit reseal the strands. The DNA gyrase consists of two A subunits and two B subunits. This is necessary to prevent excessive positive supercoiling of the strands when they separate to permit replication or transcription. ![]() The fluoroquinolones (FQ) inhibit the enzyme bacterial DNA gyrase, which nicks the double-stranded DNA, introduces negative supercoils and then reseals the nicked ends. Tetracyclines, such as tetracycline, chlortetracycline, doxycycline, or minocycline, act upon the conserved sequences of the 16S r-RNA of the 30S ribosomal subunit to prevent binding of t-RNA to the A site. They cause misreading and premature termination of translation of mRNA. AG's interact with the 16S r-RNA of the 30S subunit near the A site through hydrogen bonds. These AG have synergism with those antibiotics, which inhibit cell wall synthesis (such as β-lactam and glycopeptides) as it allows greater penetration of AG within the cell and at low dosages. For these reasons, AG work in aerobic conditions and have poor activity against anaerobic bacteria. The main target of action is bacterial ribosome to enter, there it must pass through cytoplasmic membrane requiring energy dependent active bacterial transport mechanism, which requires oxygen and an active proton motive force. The aminoglycosides (AG's) are positively-charged molecules which attach to the OM which is negatively charged leading to formation of large pores, and thus allow antibiotic penetration inside the bacterium. This review discusses the mechanism of action and resistance development in commonly used antimicrobials. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. Infections account for a major cause of death throughout the developing world. ![]()
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