Antibiotic Resistance Flashcards
Why have microorganisms developed antibiotics?
To fight against other microorganisms for resources and for quorum sensing (communication and co-operative interactions between organisms of the same species).
How can resistance be divided for classification?
Innate and acquired resistance.
Define innate resistance.
Resistance mechanisms which the organism already has; may be evolved for another purpose other than antibiotic resistance.
Define acquired resistance.
A resistance that develops through mutations selected for by exposure to antibiotics.
Describe the innate resistance mechanism of physical exclusion.
This is the formation of a physical barrier to block compounds from entering the cell. An example of this is Gram-negative cells.
What are easier to kill with antibiotics; Gram-positive or Gram-negative bacteria? Why?
Gram-negative bacteria as they only have one cell wall which only blocks large molecules. The Gram-negative ‘double cell wall’ makes it harder to kill as it excludes smaller molecules such as antibiotic compounds.
Through what protein can certain larger molecules pass through the cell wall of bacteria?
Porins.
What are porins?
Barrel-shaped transmembrane proteins that act as passive pores.
How do aminoglycosides promote their own entry through the outer membrane?
By binding to LPS.
What antibiotics diffuse across the cell membrane by use of porins?
Beta-lactams, quinolones, tetracyclines, macrolides.
Describe the innate resistance mechanism of efflux.
Antibiotics enter the cell by way of porins or self-mediated entry, they are then pumped back out of the cell by energy-consuming efflux pumps before they can act on their targets.
Describe the innate resistance mechanism of target overproduction.
The target for antibiotics is produced at a high level so that enough of the target remains to be active even during antibiotic therapy.
Describe the innate resistance mechanism of bypassing inhibition.
Changes to the substrate specificity of an enzyme, to which an antibiotic doesn’t bind, allowing for metabolism to continue.
Apart from mutation, what other mechanisms are there for developing acquired resistance to antibiotics?
Transformation, transposition, conjugation.
With regards to acquired resistance, what is transformation?
The direct uptake of DNA containing resistance genes.
With regards to acquired resistance, what is transposition?
The movement of resistance genes from the plasmid to the genome.
With regards to acquired resistance, what is conjugation?
The transfer of plasmids between organisms.
What are the specific mechanisms of acquired resistance?
Inactivation and modification, changes in specific target proteins.
With regards to acquired resistance, what are inactivation and modification?
The action that the organism has on the chemistry of the antibiotic compound. Changing the drug so that it no longer has its desired effect.
How do changes in specific target proteins contribute to acquired resistance?
Modification of the target protein so the antibiotic doesn’t bind as effectively or at all.
What are bacteriophages?
Viruses which are designed to attack and kill bacteria.
What principles are used to mitigate the effects of developing resistance?
Careful use of current antibiotics, development of existing agents, targeting of resistance mechanisms, developing drugs active against new targets.
What criteria must be fulfilled when developing new antibiotics?
Active against the microbial target, doesn’t kill good bacteria, inactive against humans or animals, not inferior to other antibiotics used for the same target.
What are bacteriocins?
Protein or peptide antibiotics secreted by bacteria to disadvantage other bacteria.
What are antimicrobial peptides (AMPs) or host defence peptides (HDPs)?
Other bactericidal compounds which form part of innate immunity.