Monday, January 06, 2014

Bacterial Persistence- On a Note


     Before I say anything, I wish all a happy New Year (Oh, Yes, am a couple of days late wishing). Am slowly entering the 3rd Year of blogging with hopefully considerable improvement in the material. Probably the person who has gained the most from this blog is myself. It reals helps me to write down my thoughts somewhere. The downside, I have been pretty inconsistent in posting last year. Hope I can make up this year.

        Often i get into arguments with people on what mechanisms influence antibiotic resistance. Acquired antibiotic resistance is one of the important problems in chemotherapy (But not the Only). The kinetics of acquiring resistance is often quite complex. The long standing idea is there is a pre-existing mutation in one or few of the organisms that is being selected for when antibiotic is given leading to emergence of a resistant strain. That is a well credited idea. But, a couple of mutations most often will not lead to a huge leap in MIC for organism in one single replication event. As I have argued before, and still continue to debate, it requires something extra.

    Here's one scenario that often strikes me to project an explanation. Clinical Microbiologists practicing in routine patient care may have noted the following. A disc diffusion test (Usually Kirby Bauer Method), shows sensitivity to a X antibiotic. When the clinician uses the same antibiotic the patient doesn't improve. If you collect sample and isolate again, you still get sensitivity in plate to X. This is not a very common phenomenon, but not so rare either. I simply mean to state, the organism shows sensitivity in vitro and resistance invivo. Both case may be right at the same time, and technically correct.

Example mechanism of persistance. Read more here
   My explanation was that there maybe a "Bystander resistance". But there seems to be a more legitimate alternative explanation and probably, a very unexplored area. In many of my previous blog posts, I had mentioned of existence of subset of population called as persisters. Persisters are a small subgroup of the population that undergoes dormancy, making them highly resistant to the activity of drugs. The concept of persisters has been proposed almost a decade ago, but is probably taken seriously only recently. An excellent commentary is presented by Andrew Jermy.

     On a lighter note, I wish to say that gone are the days when we used to think that and teach there are 2 mechanisms of antibiotic resistance- Innate and Acquired. There are more mechanisms which doesn't fall into any of the classic categories.
Wakamoto Y, Dhar N, Chait R, Schneider K, Signorino-Gelo F, Leibler S, & McKinney JD (2013). Dynamic persistence of antibiotic-stressed mycobacteria. Science (New York, N.Y.), 339 (6115), 91-5 PMID: 23288538

Jermy A (2013). Bacterial physiology: no rest for the persisters. Nature reviews. Microbiology, 11 (3) PMID: 23334264

Wood TK, Knabel SJ, & Kwan BW (2013). Bacterial persister cell formation and dormancy. Applied and environmental microbiology, 79 (23), 7116-21 PMID: 24038684

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