I hope that my message isn’t to be considered as an unsolicited nuisance (aka spam). I would like to answer to the message you addressed to Jean Staune, which appeared as an attachment to his post on Sur-la Toile.
In fact, despite that plasmids are well known for mycobacteria, I don’t think they can explain the multi-resistant strains recently emerging. You are right at that point. I was referring essentially at transduction by mycobacteriophages, for the part HGT, and response to antibiotics-induced stress as a mechanism generating diversity.
« The first point that might be useful to emphasize arguing with Vekris is that he is most likely referring to the known phenomenon of existance of plasmids (extrachromosomal elements, relatively small pieces of DNA that can replicate independently inside the cells) that contain many different genes of resistance to different antibiotics, and other drugs, like heavy metals (Mercury, in particular). These plasmids have been shown to jump between different species of bacteria via the horizontal transfer, that he is talking about. This would instantly make bacteria resistant to several different drugs at once.
Indeed, if this was the case with Mycobacterium tuberculosis, we would have nothing to talk about, as Darwinism is still be easily compatible with this phenomenon.
However, it appears that most of the drug resistant cases in Mycobacterium Tuberculosis are not like this – they do appear as mutations in previously existing chromosomal genes. Here is just one refernece of many papers on this subject, with an abstract (I am not sure that is the most autoritative group, and if necessary something better can be pulled from Medline) »
Now, recombination between plasmids and chromosomal elements is a common phenomenon, so even if primary mutations are on chromosomal genes they may be carried by plasmids afterwards. And this is the same with any genetic element known to recombine with chromosomal DNA and spreading across individuals of the same or different species. And plasmids aren’t always small pieces, mycobacterial ones make it to up to 320 kb, that’s around 7% of the tuberculosis chromosome.
HGT is know to occur naturally in mycobacteria (also). I don’t understand why you consider pointing to the HGT database as irrelevant. It’s an evidence that such transfers occurs.
The most pertinent part of your comment is the last paragraph.
« Or would not it? As far as I understand (but it should be checked) – the multidrug therapy is based on parallel treatment of the patient with all four (or seven?) drugs altogether. Thus, it would not be of any advantage for a bacterial to have only one mutation – it will die anyway, because the three other drugs will be enough to kill it. Thus, the hypothetical intermediates in this scheme (independent mutations in different genes conferring mutations to different drugs) would not exist. I repeat, this depends on how strictly the therapeutic protocols are actually followed in the hospitals. It is hard to know, and it is kind of ironic that the fate of Darwinism is depending on how honest the doctros are:-) However, as McFadden notices, we should also expect that these intermediates would be isolated from patients, and they were not. »
First, the last point: there are plenty of intermediaries known between sensible M. tuberculosis and the multi-resistant XDR-TB causing ones. Simple, double, triple, quadruple etc. resistant strains.
WHO defines XDR-TB strains as MDR-TB with additional resistance (http://www.who.int/mediacentre/news/notes/2006/np23/en/index.html« MDR-TB (Multidrug Resistant TB) describes strains of tuberculosis that are resistant to at least the two main first-line TB drugs – isoniazid and rifampicin. XDR-TB, or Extensive Drug Resistant TB (also referred to as Extreme Drug Resistance) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. »)
Why McFadden don’t mention them? Great question. Why McFadden don’t consider plasmids and mycobacteriophages causing HGT once chromosomal mutations occurred? I don’t have any answers that wouldn’t be insulting for Dr McFadden, do you?
Now, the first part: is it possible for a non-ressistant strain to develop multi-resistance if treated simultaneously with several antibiotics? Or, rephrased, do we know how this would be possible?
An hyper-mutator, able to overcome deleterious mutations, presenting the possibility for intensive recombination between several genomes would be ‘one’ of the solutions, isn’t it? Without the ‘immediate need’ for horizontal gene transfer.
There is a mechanism increasing the rate of mutations of mycobacteria under stress, including drug induced stress : DnaE2 Polymerase Contributes to In Vivo Survival and the Emergence of Drug Resistance in Mycobacterium tuberculosis, Helena I.M. Boshoff, Michael B. Reed, Clifton E. Barry III and Valerie Mizrahi, Cell, Vol. 113, 183–193, April 18, 2003
What about escaping deleterious mutations and increased recombination levels?
The ‘best’ would be to have several genomes in the same ‘cell’, a syncytium, result of inhibited septation.
Such an inhibition is known by beta-lactam antibiotics (Morphological changes induced by beta-lactam antibiotics in Mycobacterium avium-intracellulare complex, Y Mizuguchi, M Ogawa, and T Udou, Antimicrob Agents Chemother. 1985 April; 27(4): 541–547). But it make ‘necessary’ the presence of additional elements (common in patients with multiple infections such as those observed in AIDS).
It is more convenient to consider that, at least, M. tuberculosis present such a state naturally, when infecting macrophages: Mycobacterium tuberculosis Cells Growing in Macrophages Are Filamentous and Deficient in FtsZ Rings, Ashwini Chauhan, Murty V. V. S. Madiraju, Marek Fol, Hava Lofton, Erin Maloney, Robert Reynolds, and Malini Rajagopalan, J Bacteriol. 2006 March; 188(5): 1856–1865.
So, the ‘ingredients’ are all in place, without the ‘necessity’ to consider poorly managed TB care. In fact, such low quality health care is observed, not as a consequence of « how honest the doctors » are, but rather « incorrect drug prescribing practices by providers, poor quality drugs or erratic supply of drugs, and also patient non-adherence » (same WHO reference as above).
I would like to add that there is nothing « darwinian » or not about that. It is rather a question of trying to explain the mechanisms that lead to observed results without supporting one or another ideology.
My main point criticizing Jean Staune’s book was to demonstrate that the field wasn’t completely covered, as he claims, and that a lot of knowledge was simply left aside, probably because it doesn’t fit with his ideology.
I think that the fact that he ignored or eluded (directly or based on McFadden’s assertions) HGT and known hypermutating states of mycobacteria makes the point.
Jean Staune thinks that such matters are « debatable ». I consider that as far as the lab work to explain observations isn’t finished, it is an error publishing partial observations, especially in general public books, trying to legitimate opinions/ideology on the basis of poor analysis; if any.
Staune said on Sur-la-Toile that you read his book and found nothing to object about the multi-resistance of Mt.
Grâce à Vasily Ogryzko généticien de classe internationale et directeur de recherches à l’INSERM j’ai pu avoir accès à l’avis de généticiens de très haut niveau qui confirment que les mutations adaptatives restent en partie un mystère pour le darwinisme (en passant Vasily n’a rien trouvé à redire au passage sur la multirésistance , j’en conclu que l’argument est solide) »
Is it true?
A. Vekris (aka OldCola)