How can antibiotics act selectively against bacteria? Why may antibiotics have no effect on bacteria? Describe the main bacterial antibiotic resistance mechanisms.
Antibiotics are selectively toxic against bacteria because bacteria differs greatly from human cells, mainly the bacteria have cell walls that for the outer boundary of the cell. The type of wall a bacterium has is one factor that determines which antibiotic can kill it. Some antibiotics selectively kill either gram positive bacteria or gram negative bacteria (narrow spectrum) eg. Vancomycin that selectively kills gram positive bacteria like staphylococcus, streptococcus and enterococcus. Broad spectrum antibiotics will kill gram positive and negative, but no antibiotic can kill all bacteria. the sites of action of main antibiotics include peptidoglycan synthesis (beta lactams- causing the bacteria to lyse), protein synthesis, nucleic acid synthesis, biosynthesis of folic acid (starve bacteria), DNA replication, transcription and cytoplasmic membrane integrity.
Gram negative bacteria have less peptidoclycan in their cell wall and are more antibiotic resistant than gram positive bacteria. Some of the bacteria might no have an effect on the bacteria unless they are combined with an antibiotic that breaks down the cell wall, because they wont get into the bacteria to have their effect. E.g. sulphonamides, aminoglycosides, tetracylines, cloramphenicols and Linchosamides,macrolides. Efflux pump pumping these out of the bacteria will also be an important reason for developing resistance.
There are resistance genes that inactivated antibiotics.
Hydrolysis that inhibit Beta lactams with beta lactamase occurs in both gram negative and positive bacteria. Penicillin G has a huge resistance and there is therefore need to develop beta lactamase resistant beta lactams like methicillin. One can also give beta lactamase inhibitor.
Chemical modification: aminoglycosisdes or chloramphenicols are altered so that its prevented to bind to its target site.
Active efflux pump will actively pump antibiotics out of the cytoplasma so that it cant reach its target site.
Alteration of the target site can happen if aquires a gene for altered penicillin binding protein from another organism like MRSA. Macrolides are chemical mediators of antibiotic binding sites with reisitance enzyme methylate 2 adeninne which prevent antibiotic binding.
Metabolic byplass can happen when the plasma codes variance of enzymes giving a lower affinity to the antibiotic. This occurs with suphonamides and trimethoprim.
sometimes the resistance is gene is passed on to clinical bacteria. Evolution of multi R plasmid will help transmit resistant genes to different bacteria. S.typhimuruim was an example of a clone that is multi-resistant to antibiotics, its now banned
Discuss how antibiotics can interfere with peptidoglycan and protein biosynthesis. Discuss why antibiotics may have no effect on bacteria.
Peptidoglycan is in the bacteria cell wall causing rigidity and strength due to the peptide bonds. It causes the cell wall of the bacteria and protects it, because the bacteria will lyse without it. (except for a few.e.g mycoplasma). Peptidoglycan will grow outside the membrane but synthesis precursors in the cytoplasm and transport the precurors across the cell membrane by specific transport proteins. Glucopeptides will inhibit the action of the precursors to the peptidoglycan. Beta lactams will inhibit cross linking (e.g. penicillin). Penicillin and cephalosporins compromises the largest and most important class of antibacterial drugs which inhibit cell wall synthesis. Whilst a number inhibit protein synthesis. Aminoglycosides bind to 30s ribosomal subunit and affect a number of different steps in protein synthesis. Macrolides inhibit protein synthesis by inhibiting 50s ribosome subunit. Drugs which act synergistically including sulponamides and trimethorprim act at two different sites in the folic acid pathway, and clavulanic acid and penicillin combination inhibit beta lactamase activity and therefore prevent the inactivation of penicillin.
Beta lactam antibiotics involved binding to the receptor known as penicillin binding protein and cause the bacteria to lyse by interfering with the crosslinking of peptidoglycan in the cell wall of the bacteria. Bacteria which produces beta lactamases are resistant to beta lactam antibiotics because beta lactamase cleave the beta lactams rings, rendering the antibiotic ineffective. These enzymes may be plasma mediated, as in staphylococci, or they may be chromosomally encoded as in gram negative bacteria. Resistant genes can be transferred between bacteria through transduction, conjugation, transponsable elements or transformation. Resistance to an antibacterial agent often results in cross resistance to other agents in the same plass. Mechanisms producing resistance to antibacterial drugs include production of enzymes by bacteria which destroy or inactivate the drug and reduction of bacterial cell permeability. Bacteria may also develop alternative metabolic pathways to those inhibited by the drug. The antibiotic may be eliminated from the cell(efflux pump), or the target site of the drug might be structurally altered. Bacterial resistance is widespread and control measures are being put into place to prevent the resistant bacteria reaching the human populations. This will most often result in the antibiotic class being banned for use in animal.