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 Bacterial Resistance to Antibiotics (page 3) (This chapter has 4 pages) © Kenneth Todar, PhD Bacterial mechanisms of antibiotic resistance Several mechanisms have evolved in bacteria which confer them with antibiotic resistance. These mechanisms can either chemically modify the antibiotic, render it inactive through physical removal from the cell, or modify target site so that it is not recognized by the antibiotic. The most common mode is enzymatic inactivation of the antibiotic. An existing cellular enzyme is modified to react with the antibiotic in such a way that it no longer affects the microorganism. An alternative strategy utilized by many bacteria is the alteration of the antibiotic target site. These and other mechanisms are shown in the the figure and accompanying table below.
Three mechanisms of antibiotic resistance in bacteria. Most, but not all, resistance mechanisms are encoded by plasmids, which are potentially transmissible to other bacteria. Clockwise. 12 o'clock: Efflux pumps are high-affinity reverse transport systems located in the membrane that transport the antibiotic out of the cell. This is the mechanism of resistance to tetracycline. 4 o'clock: A specific enzyme modifies the antibiotic in a way that it loses its activity. In the case of streptomycin, the antibiotic is chemically modified so that it will no longer bind to the ribosome to block protein synthesis. 9 o'clock: An enzyme is produced that degrades the antibiotic, thereby inactivating it. For example, the penicillinases are a group of beta-lactamase enzymes that cleave the beta lactam ring of the penicillin molecule.
The development of resistance is inevitable following the introduction of a new antibiotic. Initial rates of resistance to new drugs are normally on the order of 1%. However, modern uses of antibiotics have caused a huge increase in the number of resistant bacteria. In fact, within 8-12 years after wide-spread use, strains resistant to multiple drugs become widespread. Multiple drug resistant strains of some bacteria have reached the proportion that virtually no antibiotics are available for treatment. Antibiotic resistance in bacteria may be an inherent trait of the organism (e.g. a particular type of cell wall structure) that renders it naturally resistant, or it may be acquired by means of mutation in its own DNA or acquisition of resistance-conferring DNA from another source. Inherent (natural) resistance. Bacteria may be inherently resistant to an antibiotic. For example, an organism lacks a transport system for an antibiotic; or an organism lacks the target of the antibiotic molecule; or, as in the case of Gram-negative bacteria, the cell wall is covered with an outer membrane that establishes a permeability barrier against the antibiotic. Acquired resistance. Several mechanisms are developed by bacteria in order to acquire resistance to antibiotics. All require either the modification of existing genetic material or the acquisition of new genetic material from another source. Vertical gene transfer Once the resistance genes have developed, they are transferred directly to all the bacteria's progeny during DNA replication. This is known as vertical gene transfer or vertical evolution. The process is strictly a matter of Darwinian evolution driven by principles of natural selection: a spontaneous mutation in the bacterial chromosome imparts resistance to a member of the bacterial population. In the selective environment of the antibiotic, the wild type (non mutants) are killed and the resistant mutant is allowed to grow and flourish Horizontal gene transfer There are at least three possible mechanisms of HGT, equivalent to the three processes of genetic exchange in bacteria. These are transduction, transformation or conjugation. Transformation is a process where parts of DNA are taken up by the bacteria from the external environment. This DNA is normally present in the external environment due to the death and lysis of another bacterium. Transduction occurs when bacteria-specific viruses (bacteriophages) transfer DNA between two closely related bacteria. Mechanisms of horizontal gene transfer (HGT) in bacteria The combined effects of fast growth rates to large densities of cells, genetic processes of mutation and selection, and the ability to exchange genes, account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial adaptation (resistance) to the antibiotic environment seems to take place very rapidly in evolutionary time. Bacteria evolve fast!
chapter continued Previous Page © Kenneth Todar, Ph.D. All rights reserved. - www.textbookofbacteriology.netWhat are three causes of antibiotic resistance?Misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. Lack of clean water and sanitation and inadequate infection prevention and control promotes the spread of microbes, some of which can be resistant to antimicrobial treatment.
What are the 3 types of antibiotic resistance?Antimicrobial resistance mechanisms fall into four main categories: (1) limiting uptake of a drug; (2) modifying a drug target; (3) inactivating a drug; (4) active drug efflux.
What are 3 ways that antibiotic resistance genes work?Resistant bacteria continue to multiple, even when exposed to antibiotics; Horizontal Gene Transfer – Antibiotic-resistant genetic material is transferred between different bacteria cells. This can happen in three different ways: transformation, transduction or conjugation.
What is the process of developing antibiotic resistance?Through mutation and selection, bacteria can develop defense mechanisms against antibiotics. For example, some bacteria have developed biochemical “pumps” that can remove an antibiotic before it reaches its target, while others have evolved to produce enzymes to inactivate the antibiotic.
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Describe three different processes by which antibiotic resistance develops
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