Dynamic persistence of antibiotic-stressed mycobacteria.

[kiny]

http://www.sciencemag.org/content/339/6115/91.long

Dynamic persistence of antibiotic-stressed mycobacteria.

Wakamoto Y, Dhar N, Chait R, Schneider K, Signorino-Gelo F, Leibler S, McKinney JD.

School of Life Sciences, Swiss Federal Institute of Technology in Lausanne, Switzerland.

2013 Jan

Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.

 

[kiny]

"Our Science paper provides clear experimental proof that other mechanisms of persistence also exist, our findings necessitate the re-examination of the mechanisms of persistence at the single-cell level in other bacteria, including Mycobacterium tuberculosis, which causes TB in humans.At present we can only speculate as to whether the same or similar mechanisms exist in other bacterial species, although we think this is likely"

 

[mnsun]

Kiny, I too think there is something along the lines of a persistent virus/mycobacteria as another key causal factor of crohn's among us who are predisposed. Have you completely ruled out, or have an opinion on, systemic measles viruses--likely due to vaccine induced immune/antigen complexes?

The recent findings of two girls given Gardisil vaccines, who died as a result and had their brains dissected, showed HPV-16-L1 antigen used in Gardisil in the blood vessels of their brains. This reminded me of the apparently revolving-door-like immuno-surveillance system of intestinal cells ( http://www.sciencedaily.com/releases/2012/12/121213121755.htm ) which may specifically have to do with newly found goblet cells ( http://www.sciencedaily.com/releases/2012/03/120314142049.htm ).

These articles in addition to the older preliminary findings of Wakefield (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499879/) spurred me to find this later study: http://gut.bmj.com/content/46/2/163.full

This gut.bmj study seems odd to me. A lot of loose ends are left to fray. I think its odd that they assume that finding measles antigen (they don't hypothesize the source--ie. vaccines, imho) is perfectly normal in IBD and non-IBD patients systemically: in the jejunum, duodenum, esophagus and stomach... They don't go on to assume, like I am here, that POSSIBLY we simply have a predisposition to overreact immunologically to this "normal" systemic measles antigen.

Despite their conclusions they admit the following in the Discussion section:"Although the possibility still remains that, in the present study, the antigen recognised in colonic mucosa by 4F12 is measles virus antigen (the measles specific antigen), we assume such a possibility is extremely slight..."

Any thoughts?

 

[kiny]

Thank you, will read the study (it takes me some time to read the things, it took me a while to understand what most studies talk about, I am much better at it though, I knew nothing about crohn when I first got it)

Regarding antigen response, there's a study that shows that MAP antigen is able to induce full thickness necrotising http://www.ncbi.nlm.nih.gov/pubmed/22486997

When he says "antigen" he is talking about dead MAP, pasteurised MAP.

I also think that the issue of detection of pathogens with biopsies might give conflicting results if the primary inflammation is at the lymphatic system, in deeper layers of submucosa, which some studies have shown. Not at the mucosal barrier, I think the gut flora might mediate pathogenic entry and the dysbiosis is maybe a response to a chronic infection, but I don't think it is involved in any causality, the gut flora is not sustaining any inflammation, it might make it worse though and some commensals might exploit it. I wish there were more studies looking at the lymphatic system. Inflammation is deep in submucosa.

It's also werid that people suggest that there has to be presence of mycobacteria or other pathogens to propose a causal link, no that's not needed, it isn't the case for M leprae but we still treat people for it even though you can't even culture it.

 

[kiny]

These articles in addition to the older preliminary findings of Wakefield (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499879/) spurred me to find this later study: http://gut.bmj.com/content/46/2/163.full

Dunno, I know from school that staining techniques can very unreliable compared to DNA testing. They also don't show an antigen response, only the antigen, and only in one study. I dunno.

That it doesn't cause disease in all hosts is something that isn't a good rule to go by though, helicobacter pylori is in many people but it only causes ulcers in a very select few people.