Cpn Antibiotic Resistance

Both Hammerschlag and Stratton observed in their research that Cpni appeared to rapidly develop resistance against antibioticsi. Hammerschlag noted that she searched gene databanks for known resistance genesi but found no matches. I also spent a great deal of time searching the Genbank using BLAST and also found no matches to any known resistance genes. Nonetheless apparent resistance is always noted during in vitro experiments with antibiotics. All antibiotics that Cpn are susceptible to cause an initial die off of greater than 90% of Cpn. This invariably levels off and there is little die off after the first 24-48 hours. 

In vivo there is apparent resistance in diseasesi thought to be caused by Cpn as there will often be a big initial improvement when taking a new antibiotic. For example years ago I took a larger than normal initial dose (450 mg) of rifabutin after not taking it for the preceding year. In that experiment my health improved dramatically. I felt better than I had any idea one could feel. Unfortunately I was not taking NACi back then and the improvement only lasted a week or two as presumably the dead Cpn were replaced by EBs that would not have been killed.

The most common mechanism of antibiotic resistance is via efflux pumps. These are small proteins that pump out a specific molecule(s) and lower its concentration within the bacteria. There are a large number of these that have been identified and they are often shared between bacteria as they come into contact with others. They tend to be very specific, i.e. there are several for tetracyclines (TetA, TetB) and macrolides (MacA, MacB). Their specificity is important as these pumps are metabolically expensive and if they pumped out molecules that would otherwise not be a danger to the bacteria, it would limit the bacteria's viability as there is limited energy availability. Also the fact that these extracellular bacteria replicate rapidly and share DNA lends to the approach of allowing creation of very targeted pumps.

Cpn has a completely different life style than most other bacteria that may have led to a different evolutionary pathway in dealing with antimicrobial agents. First it is an obligate intracellulari pathogen which means that it interacts far less with other bacteria which would not lend itself to rapid development of needed pumps. Also it tends to grow more slowly than other bacteria which would also work against it developing a number of specific pumps. However it does have availability of almost unlimited supplies of ATP which is needed to drive these efflux pumps. The host cells that it infects oftentimes have hundreds or even thousands of mitochondria that are producing ATP in a highly efficient manner. Whereas Cpn can produce only 2 ATP molecules per glucose molecule, mitochondria produce 30 ATP. So Cpn can expend large amounts of ATP removing harmful molecules and even “waste” energy pumping out harmless molecules that are not needed for its growth or survival.

I think Cpn have evolved down the path of pumping out all substances that are not needed. If this is the case it would follow that none of the efflux pumps that Cpn has would be conserved by other bacteria as these multi substance pumps would not be beneficial to other bacteria. Also it would follow that Cpn would have none of these targeted, resistance efflux pumps as these would be redundant. And in fact there does not seem to be any overlap between the efflux pumps Cpn encodes and those of other bacteria. Cpn does have about a dozen ATP driven efflux pumps that are for the most part unidentified. It seems possible that many of these are capable of pumping out antimicrobial agents. This is not to say that killing Cpn with antibiotics is not possible. In fact I think understanding its strengths can also lead to finding its weaknesses such as the example I mentioned above.

- Paul

Hi Paul,

did you successfully eradicate Cpni?

Helen

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Doing Thibault protocol (NACi/minoi/roxi/tinii/nattokinase)...but considering morphing to Stratton protocol

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