Antibiotic Resistance Mechanisms of Bacteria
Bacterial Resistance to Antimicrobials is Significant and Important
Oct 12, 2009
The early era of antibiotics marked the discovery of effective antimicrobials and antibiotics. From 1900-1960 there was great hope that infectious diseases caused by bacteria could be defeated. Ehrlich's synthesis and discovery of salvarsan, compound 606, Domagk's development of prontosil, Fleming's penicillin and Waksman's streptomycin antibiotic discoveries filled the air with one new hope after another. Streptococci, staphylococci, and syphilis, gonorrhea, plague were, respectively, bacteria and diseases subject to medicine's firm hand, until that fateful time when microbiologists and doctors saw microbial clenched fists held high — multiple-antibiotic resistance had clearly emerged. In 1961, emerging methicillin-resistant staphylococci was a disturbing theme, and resistance continues to develop and expand even today.
Antibiotic Resistance by Mutation and Selection
Typical gastrointestinal bacteria divide and multiply quickly, needing only 15-20 minutes to double by binary fission. The human large intestine contains about 100 billion bacteria per gram of solid matter and over 100 different species of bacteria.
Bacteria grow rapidly and mutate rapidly at a rate of 1 in every 100,000 to 1 in every million. Mutations are random events, and typically are not caused by antibiotics.
When mutations occur, biochemical changes often occur. A membrane protein, enzyme, or ribosome may be altered. DNA base pair mutations often translate into single, different amino acid changes in the protein with accompanying changes in protein shape, or function, or both. The many potential mutations, anywhere along a DNA molecule (the basic hereditary material), increase the chances for development of antibiotic-resistant bacteria.
Antibiotic Resistance by Transformation, Transduction and Conjugation
DNA and associated traits – such as antibiotic resistance – may be transferred between bacteria. DNA transfers may be rare, or fairly common, depending upon circumstances. Large populations of closely-related bacteria increase the chances for gene transfer, including resistance genes, which are among the preferred bacterial gene transfers. The three common gene transfers are:
- Transformation – DNA escapes from damaged or dying cells, and live bacterial cells uptake one strand of the genes and incorporate those into the full DNA gene package..
- Conjugation – One bacterium attaches to another bacterium via a pilus (protein transfer tube) that transfers a portion of its genes to a receiving bacterium. Examples are F+ or Hfr bacteria that transfer to F- bacterium. One, or many genes, may be passed in this manner.
- Transduction – A virus carries a portion of one bacterium's genes into another bacterium. The virus attaches to the bacterium, injects viral and some bacterial DNA, which becomes incorporated into the host, recipient bacterium. If the bacterium survives the infection and multiplies, that gene is maintained and passed on to all offspring bacteria.
The article photo below, when clicked, enlarges and summarizes all three gene transfer mechanisms.
Types of Antibiotics and Their Antibacterial Activities
The antibiotic antibacterial activity includes:
- membranes - distortion and damage with leakage of vital cell materials and death. Examples: polymyxin B, colistin.
- walls - inhibition of cell wall synthesis of glycopeptide (peptidoglycan). Weakened walls cause osmotic bursting. Examples: penicillin, cephalosporins, bacitracin, monobactams, carbapenems.
- ribosomes - interference with mRNA, tRNA, ribosomes. Examples – amikacin, azithromycin, chloramphenicol, clarithromycin, doxycycline, gentamycin, kanamycin, minicycline, streptomycin, neomycin, netilmycin, tetracycline, tobramycin.
- nucleic acids - interfere with the DNA or RNA structure, synthesis or functions. Examples: rifampin, naldixic acid, quinolones.
- competitive inhibition - e.g. sulfa drugs involved with PABA and folic acid synthesis. Examples: sulfonamides, sulfadiazine
Antibiotics may inhibit or kill microbes, but macrophages (monocytes) and neutrophils ingest and destroy bacteria, and the entire host immune system ultimately accounts for host survival.
Molecular Mechanisms of Antibiotic Resistance
Here are some ways antibiotics may be inactivated:
- Membrane changes block antibiotic entrance and penetration into the cell.
- Enzymes degrade antibiotics, or inactivate them by reactions of: phosphorylation, adenylation, or acetylation.
- Ribosomes become altered, mutated, and chemical-physical changes prevent antibiotic attachment to those ribosomes.
- Molecular pumps energetically transfer antibiotics out of the cell.
The world of prokaryotes, the simplest of cells, is far from simple.
Sources
Brooks, G.F., J.S. Butel and S. A. Moore. 2004. Medical Microbiology. 23rd ed., Lange Medical Books, McGraw-Hill, New York. 818pp
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