Eradication of Biofilm-Like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime
Jie Feng,
Megan Weitner,
Wanliang Shi,
Shuo Zhang and
Ying Zhang*
- Department of Molecular Microbiology and Immunology,
Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
MD, USA
Lyme disease, caused by
Borrelia burgdorferi, is the most
common vector-borne disease in the United States and Europe. While the
majority of Lyme disease patients can resolve their symptoms if treated
promptly, 10–20% of patients suffer from prolonged symptoms called
post-treatment Lyme disease syndrome (PTLDS). Although the cause for
PTLDS is unclear, one possibility is the presence of bacterial
persisters not effectively cleared by the current Lyme antibiotics.
Recent studies identified several drug candidates including daptomycin,
daunomycin, doxorubicin, and mitomycin C that had good activity against
B. burgdorferi persisters. However, their relative activities against
B. burgdorferi
persisters have not been evaluated under the same conditions. In this
study, we tested the anti-persister activities of these drugs against
both 7-day and 15-day old stationary phase cultures of
B. burgdorferi
individually as well as in combination with Lyme antibiotics
doxycycline and cefuroxime (Ceftin). Our findings demonstrate daunomycin
and daptomycin were more active than mitomycin C in single drug
comparison at 10 and 20 μM, as well as in drug combinations with
doxycycline and cefuroxime. In addition, daunomycin was more active than
doxorubicin which correlated with their ability to stain and accumulate
in
B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of
B. burgdorferi
persisters. However, the addition of either daunomycin or daptomycin to
the doxycycline + cefuroxime combination completely eradicated the
biofilm-like structures and produced no visible bacterial regrowth after
7 and 21 days, while the addition of doxorubicin was unable to prevent
regrowth at either 7 or 21 day subculture. Mitomycin C in combination
with doxycycline and cefuroxime caused no regrowth at 7 days but visible
spirochetal regrowth occurred after 21 day subculture. Furthermore, we
found that cefuroxime (Ceftin), the third commonly used and most active
antibiotic to treat Lyme disease, could replace cefoperazone (a drug no
longer available in the US) in the daptomycin + doxycycline combination
with complete eradication of the biofilm-like structures as shown by
lack of any regrowth in subcultures. Our findings may have implications
for improved treatment of Lyme disease.
http://journal.frontiersin.org/article/10.3389/fmicb.2016.00062/full
The latest article from Dr Zhang and his team at Johns Hopkins for earlier studies see -
http://lookingatlyme.blogspot.co.uk/2015/10/lyme-disease-persister-drugs-dr-ying.html
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