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Tag : Persisters

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Interview with Prof. Ying Zhang at the NorVect Conference 2015

Prof Ying Zhang from John Hopkins Bloomberg School of Public Health explains why Lyme disease is so difficult to treat. Having worked with Tuberculosis (TB) for many years, he sees the similarities and differences between these to bacteria. With Tuberculosis it is known that you have to treat with certain drug combinations that kill the growing form and the non-growing form (persisters) and if you treat shorter than 6 months, the patient will get a relapse.

The bacterium that causes Lyme disease is much more advanced than the TB bacterium, and the main reason is that it also takes a persisting form. These persister forms of the Borrelia bacteria cannot be cultured.

The two views – ILADS and IDSA are two different ways of seeing the same disease. Prof. Zhang thinks they are both right. When it comes to acute Lyme disease, IDSA is right. Then you only need shorter courses of treatment. When the disease turns chronic, longer courses of treatment with the right drug combinations are needed (ILADS view).

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Borrelia burgdorferi forms drug-tolerant persister cells.

A new study published in Antimicrobial Agents and Chemotheraphy shows that Borrelia burgdorferi bacteria form drug-resistant persister cells that are not easily killed by antibiotics.

Link to article here

En ny studie viser at borrelia bakterien ikke blir drept av standard antibiotikabehandling som gis her i Norge. Bakteriene kapsler seg inn for å beskytte seg mot immunsystemet og antimikrobiell behandling. Dette kan være en årsak til at mange får tilbakefall etter behandlingsstopp.

Link til engelsk artikkel her

Dieterle silver stain of genital culture from Patient 12. Note darkly staining spirochete. Formalin fixed slide, 400× magnification

 

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New research from Prof. Zhang on persister drugs

Ying Zhang Ph.D, MD, who spoke at the NorVect conference this past weekend has published very interesting new research today in the journal “Emerging Microbes & Infections”.

Ying Zhang

BACKGROUND:
Several studies (incl. animal models) have indicated the continued presence of B. burgdorferi in some form and suggest that current Lyme treatment may not be sufficient to eliminate B. burgdorferi persisters, or that the immune system fails to clear persisting organisms or bacterial debris, which may be underlying causes for those who suffer from non-resolving symptoms of Lyme disease. To date, there is currently no effective antibiotic treatment or preventative strategy for those who suffer from persistent symptoms after Lyme disease.

Consistent with the difficulty to eradicate B. burgdorferi in animal models, B. burgdorferi develops various morphological variant forms, such as round bodies and microcolonies, that are refractory or resistant to antibiotics and stresses. For example, it has been demonstrated that whereas the frontline drugs, such as doxycycline and amoxicillin, kill or inhibit the growing spirochetal form of B. burgdorferi effectively, they have little activity in killing non-growing persisters that are enriched in the stationary phase or microcolonies or as biofilm-like aggregates of B. burgdorferi. There is significant interest in the identification of drugs that target B. burgdorferi persisters.

SUMMARY AND FINDINGS:
Zhang’s research team set out to identify drugs that can more effectively kill B. burgdorferi persisters, and has recently developed a new viability assay using SYBR Green I/propidium iodide (PI) dyes, which allowed them to screen FDA-approved drug library against stationary phase B. burgdorferi persisters. Using this high-throughput assay, they identified a number of drug candidates, such as daptomycin, clofazimine, cefoperazone, and carbomycin that have excellent activity against in vitro B. burgdorferi persisters.

You can read the whole article here

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