This scientific article follows up on the research done by Dr Zhang at Johns Hopkins discussing Borrelia burgdorferi causing drug-tolerant persister cells. As per Dr Sharma and Dr Hu: "In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of B. burgdorferi to form persisters. Killing of growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from exponential to stationary phase. Combinations of antibiotics did not improve killing.
Daptomycin, a membrane-active bactericidal antibiotic, killed stationary phase cells, but not persisters. Mitomycin C, an anti-cancer agent that forms adducts with DNA, killed persisters and eradicated both growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse-dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and antibiotic was added again. Four pulse-doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture".
This article implies that pulse dose antibiotics with Daptomycin, Mitomycin and Rocephin may be helpful in culture. Limitations of this research includes the choice of medications used, as well as not being an in vitro study. Other limitations include Mitomycin being a cancer drug not commonly used in Lyme disease and the study doesn't address bacteria that are difficult to kill in the intracellular compartment, in biofilm colonies and in cystic forms, or those bacteria that may be deep in tissues where antibiotics don't penetrate well. This is an encouraging study however, as researchers are finally admitting that persister cells exist in Lyme disease as they do in other chronic infectious diseases. Co-infections, such as Babesia, Bartonella were also not addressed in this study, and the majority of my patients who are chronically ill have multiple overlapping co-infections, and improve once those co-infections are adequately treated. Further studies are needed to evaluate combination and pulse therapies in Lyme disease, as well as evaluating combination therapies for associated co-infections.
Daptomycin, a membrane-active bactericidal antibiotic, killed stationary phase cells, but not persisters. Mitomycin C, an anti-cancer agent that forms adducts with DNA, killed persisters and eradicated both growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse-dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and antibiotic was added again. Four pulse-doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture".
This article implies that pulse dose antibiotics with Daptomycin, Mitomycin and Rocephin may be helpful in culture. Limitations of this research includes the choice of medications used, as well as not being an in vitro study. Other limitations include Mitomycin being a cancer drug not commonly used in Lyme disease and the study doesn't address bacteria that are difficult to kill in the intracellular compartment, in biofilm colonies and in cystic forms, or those bacteria that may be deep in tissues where antibiotics don't penetrate well. This is an encouraging study however, as researchers are finally admitting that persister cells exist in Lyme disease as they do in other chronic infectious diseases. Co-infections, such as Babesia, Bartonella were also not addressed in this study, and the majority of my patients who are chronically ill have multiple overlapping co-infections, and improve once those co-infections are adequately treated. Further studies are needed to evaluate combination and pulse therapies in Lyme disease, as well as evaluating combination therapies for associated co-infections.
