Continuing its dominance in driving advances in our understanding of Borrelia burgdorferi persistence, Global Lyme Alliance funded a study by Monica E. Embers, Ph.D. (Tulane University) recently published in Frontiers in Microbiology titled “The Functional and Molecular Effects of Doxycycline Treatment on Borrelia burgdorferi Phenotype”. This study is the first of its kind to identify specific changes in B. burgdorferi gene activity associated with Doxycycline exposure that results in the formation of antibiotic-tolerant persisters. Identifying persister-associated genes is of critical importance as such knowledge can reveal novel targets for antimicrobial intervention.
In the current study, next-generation RNA sequencing was performed on doxycycline-treated spirochetes and treated spirochetes following regrowth, comparing them to untreated B. burgdorferi. A number of genes were perturbed and most of those which were statistically significant were down-regulated in the treated versus the untreated or treated/re-grown. Genes upregulated in the treated B. burgdorferi included a number of erp genes, which encode surface-exposed outer membrane proteins (Osps) that are produced during the initial stages of mammalian infection. Among those genes associated with post-treatment regrowth were many of the ‘usual suspects’ or best studied borrelial proteins OspA, OspB, and OspC, to name a few.
Studies also funded by GLA are currently underway to determine if these same genes are perturbed in B. burgdorferi treated with Doxycycline in a mammalian host environment.
Click here to read study abstract.
image: Illustration of Doxycycline