Environ Microbiol. 2017 Aug 24. doi: 10.1111/1462-2920.13897. [Epub ahead of print]

Sleeper cells: The stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle.

Cabello FC1, Godfrey HP2, Bugrysheva J1,3, Newman SA4.

Abstract

Infections with tick-transmitted Borreliella (Borrelia) burgdorferi, the cause of Lyme disease, represent an increasingly large public health problem in North America and Europe. The ability of these spirochetes to maintain themselves for extended periods of time in their tick vectors and vertebrate reservoirs is crucial for continuance of the enzootic cycle as well as for the increasing exposure of humans to them. The stringent response mediated by the alarmone (p)ppGpp has been determined to be a master regulator in B. burgdorferi. It modulates the expression of identified and unidentified open reading frames needed to deal with and overcome the many nutritional stresses and other challenges faced by the spirochete in ticks and animal reservoirs. The metabolic and morphologic changes resulting from activation of the stringent response in B. burgdorferi may also be involved in the recently described non-genetic phenotypic phenomenon of tolerance to otherwise lethal doses of antimicrobials and to other antimicrobial activities. It may thus constitute a linchpin in multiple aspects of infections with Lyme disease borrelia, providing a link between the micro-ecological challenges of its enzootic life-cycle and long-term residence in the tissues of its animal reservoirs, with the evolutionary side-effect of potential persistence in incidental human hosts.

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**Comment**

The idea of sleeper/persistent cells in Lyme and other TBI’s is nothing new to those actively treating patients.  It’s just a matter of time before enough people in power positions acknowledge it.  Also, it needs to be understood that those infected with Lyme often have numerous pathogens that don’t respond well to the mono therapy of Doxycycline and is one reason outcomes are not good.

For more on persistent infection:  https://madisonarealymesupportgroup.com/2017/05/10/chronic-lyme-disease-a-case-definition-at-last/

https://madisonarealymesupportgroup.com/2017/08/18/drexel-prof-lyme-persists/

https://madisonarealymesupportgroup.com/2016/12/21/dr-zhang-on-persisters/