Antibiotic resistance

Descripción

From the 12-03-14 Drugs and Disease lecture.
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Resumen del Recurso

Pregunta Respuesta
What is acquired resistance? Acquired resistance refers to situations in which a drug has previously been effective but no longer is.
What is intrinsic resistance? A situation in which a drug could never be effective because of a cell feature, such as the Gram negative bacterial outer membrane containing such tightly packed proteins and glycoproteins that vancomycin, a large antibiotic, cannot pass through the membrane.
Which two types of events does acquired resistance develop as a result of? A mutational of transmissible event - and this is usually a result of selective pressure exerted on a bacterial population during antibiotic therapy.
Mutational resistance occurs s------------ and r-------, and, if it confers resistance to an antibacterial agent in the environment, the bacterium will survive and proliferate while sensitive bacteria die. Spontaneously and randomly.
How rapidly/frequently do some E. coli strain divide? ~one every 20 minutes
The frequency of division of some bacterial species/strains increases the likelihood of mutational events. What are the ways in which a bacterium conferring resistance to an antibiotic agent might transfer this resistance (other than simple division)? Passive - transformation or transduction - or active - conjugation.
What is transformation and how does it result in the acquisition of resistance genes? Transformation is a passive transferal mechanism for acquired antibiotic resistance. A bacterium with a resistance gene is lysed and its naked DNA is taken up by proximal, intact bacterial cells, which are naturally 'competent' because they can take up DNA in the environment. As long as the donor DNA is not disintegrated by the recipient bacterium, it will be integrated into the recipient's genome.
What is transduction and how does it confer acquired antibiotic resistance? Another passive mechanism for acquiring resistance. Plasmid DNA is enclosed in a bacteriophage and transferred from the original resistant cell to the next cell to be infected. This is clinically important in the transmission of resistance genes between strains of staphylococci and of streptococci.
What is conjugation and how does it confer acquired antibiotic resistance? An active mechanism of acquired antibiotic resistance. A pilus is extended from one bacterium to another and genetic material is transferred unidirectionally. This genetic material may be chromosomal or extrachromosomal, for example a plasmid, which are replicated independently of DNA and are the main component in conferring resistance to antibacterial agents. These plasmids may contain a resistance gene which has resulted from a spontaneous mutational event, or which has resulted from insertion of a transposon into a plasmid (either from chromosomal DNA or from another plasmid) which is then transferred to another bacterium during conjugation.
Can resistance genes ever confer resistance to more than one antibacterial agent? Yes, resistance genes may confer resistance to an entire class of antibacterial agents, or multiple transposons may be inserted into a plasmid, conferring resistance to a maximum of up to 5 or 6 antibacterial agents - these mechanisms are resulting in the prevalence of highly resistant strains e.g. methicillin-resistant Staphylococcus aureus.
How might resistance genes confer resistance? The genes conferred may encode a protein that prevents drug entry, such as a change in membrane structure, or a pump that eliminates the drug upon entry, they can modify the drug target, for instance ribosomes, so that the drug cannot affect them, and they can confer the use of different biochemical pathways so that metabolism occurs without the blocked molecules.
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