Microbes Fight Back Against Antibiotics
Mechanisms of Resistance

Microbes, have developed complex tools to combat antibiotics. Many bacteria have evolved efflux pumps, which transport antibiotics out of the organism before the drug can be effective. The antibiotic tetracycline, for example, must enter the cell and attach to the 30s ribosomal subunit in order to inhibit bacteria. Tetracycline resistant bacteria, however, remove the drug from the organisms before it can attach to the ribosome, thereby withstanding up to 100 times the therapeutic dosage of susceptible bacteria. Microbes have also evolved enzymes, which degrade the drug before it reaches the target within the microbe. This mechanism of resistance is extremely effective and the most widespread of any of the modes of resistance. Enzymes alter, and so inactivate, many antibiotics, including streptomycin, kanamycin, cephalosporin, and penicillin. Another, less common form of resistance, is the alteration of the antibiotic target within the bacteria. Instead of attacking the antibiotic, some bacteria alter the chemical structure of the target yielding several classes of antibiotics useless. Using this mechanism, resistance to rifampin, quinolones, and tetracylclines have evolved in many classes of bacteria. Thus, bacteria have evolved numerous mechanisms to combat common antibiotics. 

The fungus Penicillium notatum was allowed to grow on this plate the yellow bacterium, Micrococcus luteus was overlayed. The absence of yellow in the center of the plate shows the antibiotic effects of penicillin on this bacteria. Image from The University Edinburgh.
Transmitance of Resistance Genes
This plate analyzes the resistance of various antibiotics against the Bacillus bacteria. Bacillus bacteria that are affected by the antibiotic will not grow around the circle of antibiotic. However, the novobiocin antibiotic, identified with the arrow in the whole-plate image, is not effective against Bacillus because the bacteria has developed resistance to the antibiotic. Image from The University of Edinburgh.

The dilemma of antibiotic resistance is heightened by the numerous methods bacteria have evolved to spread resistance genes. On occasion, bacteria develop a point mutation that resists antibiotic treatment. The resistant gene can then be passed down to progeny to create more resistant bacteria. This process is called vertical genetic exchange. More frequently, microbes use horizontal genetic exchange to transmit resistant genes to bacteria other than the progeny.

Horizontal genetic exchange takes place by conjugation, transposition, transduction, and transformation. Conjugation occurs between two bacteria, one containing the resistance gene and one susceptible to the therapy. The resistance genes, encoded on small circular pieces of DNA, are copied and transferred to the susceptible bacteria. Microbes also spread resistance genes by transposition. In this process transposons, small segments of DNA, jump from bacteria to bacteria, each time leaving a copy of the resistance gene. Transduction is another frequent mechanism of resistant gene transfer. Transduction occurs when a bacteriophage, a virus specific for bacteria, carries a resistant gene. Upon infection of the bacteria the resistant gene can be incorporated in the bacterial genome, thus causing resistance. Another, method of resistant gene transfer is transformation. Transformation takes place when free DNA, encoding antibiotic resistance, is incorporated into the genome of bacteria. Thus, through different, and integrative transfer processes bacteria have evolved to resist many of the current antibiotics.

 

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