Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters, 2019, Rudenko et al

[Andy]

The survival of spirochetes from the Borrelia burgdorferi (sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation.

Both subpopulations represent the cells in different physiological states. “Dormancy” and “persistence” do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of “persisters” substituted the originally-used term “survivors”, referring to the small bacterial population of Staphylococcus that survived killing by penicillin.

The phenomenon of persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics.

Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients?

Open access, https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3495-7

 

[duncan]

Early Lyme investigators threw antibiotics at their young patients, and when those often failed, concluded that Lyme was of a viral etiology. They were wrong.

It would take a few years to realize the causative agent behind the single strain of microbe infecting neighborhoods around Lyme CT was bacterial. They immediately started different abx regimens. (Although some patients were selected to not get any treatment at all so that researchers could see how the disease might play out, but that's a different story)

When antibiotics continued to fail in too many patients, early researchers unilaterally - some patients might have argued arbitrarily - bifurcated symptoms into Major vs Minor. Major symptoms included mostly things a doctor could see or measure, eg, gross encephalitis, swollen knees, palsy, etc. Minor symptoms were things like nausea and pain and cognitive decline and balance and many other subjective measures. These doctors said they could cure Lyme in a majority of cases except for a few lingering minor symptoms that didn't amount to much more than a transient inconvenience.

So even as they began to downplay symptom severity in patients whose symptom cluster did not resolve with treatment, they were willing to admit that anywhere from 10% to 40% or more of treated patients didn't recover. As we got closer to diagnostic standardization, and the associated windfall from a bourgeoning diagnostics market (thank you Bayh-Dole Act), and the looming opportunities associated with vaccines, that number shrank until it was pretty much accepted at 10% to 20%. But 10-20% of just a few thousand each year of a hard to get easy to cure infection was no big deal.

We now know that currently over 400,000 cases of Lyme occur each year in the US alone. That number climbs annually. The 10% to 20% number now appears alarmingly large. So an Old Guard study found back in 2015 or there abouts that really less than 5% of treated patients reported persistent symptoms after several years. Lyme advocates quickly pointed out that this study concentrated on early stage Lyme. It seemed to ignore patients who were failed by the diagnostic protocol and never got treatment until after Borrelia had coursed through their bodies and entered privileged sites, where abx had a hard time reaching and when it could, was met by biofilms etc.

If those victims were included, that 5% number would likely balloon. Even if it only ballooned up to 10% - the low end of the once widely acknowledged spectrum of patients who did not recover - that would mean 40,000 very sick patients, many disabled, were being added to the failed-treatment roles year after year after year.

The realization that abx believed to be effective against most strains of Bb sl - like doxy and Rocephin and amoxicillan - were actually ineffective against persister cells in vitro was a watershed moment. But the IDSA and its proxies were quick to counter that persister cells were not all that uncommon afterall, and the normal way of things would be for a patient's immune system to mop up what the abx failed to eradicate.

The problem with that logic was the bacteria at question had evolved a unique capability for fooling human immune systems. This it was truly gifted at. Bb is a little bug with a genius for eluding our immune systems' defenses, not the least of which - beyond changing shapes and building biofilms - was antigenic variation.

Between persister cells immune to most abx, and the bacteria's innate savant-type strategies to thwart the most able immune attacks, the ability to claim medical authority over a substantive portion of Lyme sufferers' infection(s) is fast fading.

I wrote this off-the-cuff, so I apologize for vagueness or any inadvertent mistakes. I think the gist is right, though.