“Anti-microbial Resistance Testing: Phenotype, Genotype and ?Proteotype”

There has long been a debate over whether the microbial genotype or phenotype is a better determinant of clinical response when looking at antimicrobial resistance testing. The genotype for antimicrobial susceptibility testing identifies genes within the microbe that have the potential to cause resistance. However it does not provide information on whether the gene is “switched on”. The phenotype is how the microbe responds to the antimicrobial in the laboratory setting, but would not pick up resistance potential, and in particular resistance genes that may code for “inducible” resistance.  There has been a trend in recent years for a move towards calling results from genotypic testing the “gold standard”. This is probably due to two factors:

  • Increased range of molecular assays for resistance determinants available.
  • Fear of not knowing the genotype and thus missing the potential for resistance.

My worry would be that genotypic resistance testing may well be over-calling anti-microbial resistance in some cases, and thus pushing patients unnecessarily towards broader spectrum antibiotics, thus starting a vicious circle of resistance. This is not something however, that is often brought up in the anti-microbial stewardship committee setting.

In addition to this confused picture, if Maldi-tof techniques start reliably detecting resistance determinants, then we will have another category to deal with. Maldi-tof in it’s current form in the diagnostic laboratory looks mainly at proteins, so we will therefore have the PROTEOTYPE. This is different from both genotype and phenotype. Although it provides information on gene expression, it still does not necessarily predict the phenotypic response.

Thus, as the process of anti-microbial susceptibility testing gets ever more complex, the number of people who fully understand it, (if anyone) diminishes further.

It may also be that as more and more genes are discovered that have the “potential” to cause resistance, the “gap” between the resistance genotype and phenotype, which is currently quite small, will continue to widen.

It’s an interesting topic, and I am sure debate on the above points will continue for generations yet.


p.s. I have downloaded some software which facilitates viewing of the website on I-phones etc.

Leave a Reply

Your email address will not be published. Required fields are marked *