Dear colleagues,
How can you define the intrinsic resistance of bacteria against anti-microbial agents ?
"Intrinsic resistance is when a bacterial species is naturally resistant to a certain antibiotic or family of antibiotics, without the need for mutation or gain of further genes. This means that these antibiotics can never be used to treat infections caused by that species of bacteria."
"An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer."
"The intrinsic antibiotic resistome is a naturally occurring phenomenon that predates antibiotic chemotherapy and is present in all bacterial species. In addition to the intrinsic resistance mediated by the bacterial outer membrane and active efflux, studies have shown that a surprising number of additional genes and genetic loci also contribute to this phenotype."
It is quite confusing for this notion and how to seperate it from spontaneous resistance / intrinsic mutated genes / other factors.
If you have any suggestion or experience please share with me
Thank you so much ,
The distinction is subtle but important. Bacteria become resistant in one of two general ways. First is expression of some resistance gene which either inactivates the antibiotic, some enzyme that cleaves the antibiotic so that it essentially is all gone. Resistance to beta-lactams (penicillin etc) are one example. In other examples the resistance element creates a pump that removes it from the cell. Resistance to tetracycline is an example. This prevents the antibiotic from acting because it is no longer in the cell.
Mutations to resistance (point mutations) occur at the target site for the antibiotic, so if the antibiotic targets a specific protein in the cell, you might be able to get mutations the change the protein so that the antibiotic no longer binds or has any effect. Mutations to rifampicin resistance or streptomycin resistance are well known examples.
Intrinsic resistance is a situation where the cells, for whatever reason, have a much higher tolerance to the antibiotic. In some cases it may be some properties of the cell membrane that reduce the ability of the antibiotic to enter the cell, or some efflux pumps that tend to pump out in a non-specfici way certain compounds and include antibiotics among them. Or it could be the target site for the antibiotic is a bit different and hence no longer an effective target. In many ways this is arbitrary and just some strains have a much higher MIC than other strains (typically E. coli being the "normal" strain).
An intrinsic resistance is present in all members of a species. This might be because this species of bacteria is expressing eflux-pumps or because the antibiotic can't enter the bacteria of a modified cellmembrane. For example vancomycin can only act upon gram-positiv bacteria and not on gram-negativ bacteria because it can not penetrate the outer-membrane of the gram-negativ bacteria. Thus all gram-negativ bacteria are intrinsicly resistant to vancomycin.
Extrinsic or spontaneous resistance only occures in a singel member of a species, for example a S. Aureus that is expressing beta-lactamase-enzymes and is thus resistent to ampicillin. The key point is, that this resistenc is not natural to this species of bacteria and had to be acquired.
EUCAST has addressed this issue too:
"EUCAST has decided to replace the term "intrinsic" with the terms "expected susceptible phenotype" and "expected resistant phenotype". For a species to be included in the "expected resistant phenotype", 90% or more should be considered resistant (Klebsiella pneumoniae vs. ampicillin is an example). For a species to be included in the "expected susceptible phenotype" the wild type should be considered susceptible (S or I) to the agent and a very high proportion (99%) of isolates should be devoid of acquired resistance to the agent (Streptococcus pyogenes vs. benzylpenicillin is one example). In both cases, susceptibility testing is best avoided. A result which goes against the expected phenotype should be viewed with suspicion."
https://www.eucast.org/expert_rules_and_expected_phenotypes/expected_phenotypes
However, clinical resistance (defined by the clinical breakpoints) differs from in-vitro resistance.
@All answering colleagues,
I am so thankful for your suggestions and evidences accordingly. Now I become confident about this definition.
Best regarding,
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