Pleomorphic Variants of Borreliella (syn. Borreliaburgdorferi Express Evolutionary Distinct Transcriptomes

1Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, HR-10000 Zagreb, Croatia
2BCA-Research, BCA-Clinic Betriebs GmbH & Co. KG, D-86159 Augsburg, Germany
3Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK
4Physics of Synthetic Biological Systems-E14, Physics Department and ZNN, Technische Universität München, D-85748 Garching, Germany
5Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, HR-10000 Zagreb, Croatia
6School of Medicine, Catholic University of Croatia, Ilica 242, HR-10000 Zagreb, Croatia
7Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, HR-10000 Zagreb, Croatia
8Comlamed, Friedrich-Bergius Ring 15, D-97076 Würzburg, Germany
*Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 202324(6), 5594;
Received: 18 February 2023 / Revised: 7 March 2023 / Accepted: 11 March 2023 / Published: 15 March 2023
(This article belongs to the Special Issue Transcriptomics in Health and Disease)


Borreliella (syn. Borreliaburgdorferi is a spirochete bacterium that causes tick-borne Lyme disease. Along its lifecycle B. burgdorferi develops several pleomorphic forms with unclear biological and medical relevance. Surprisingly, these morphotypes have never been compared at the global transcriptome level. To fill this void, we grew B. burgdorferi spirochete, round body, bleb, and biofilm-dominated cultures and recovered their transcriptomes by RNAseq profiling. We found that round bodies share similar expression profiles with spirochetes, despite their morphological differences. This sharply contrasts to blebs and biofilms that showed unique transcriptomes, profoundly distinct from spirochetes and round bodies. To better characterize differentially expressed genes in non-spirochete morphotypes, we performed functional, positional, and evolutionary enrichment analyses. Our results suggest that spirochete to round body transition relies on the delicate regulation of a relatively small number of highly conserved genes, which are located on the main chromosome and involved in translation. In contrast, spirochete to bleb or biofilm transition includes substantial reshaping of transcription profiles towards plasmids-residing and evolutionary young genes, which originated in the ancestor of Borreliaceae. Despite their abundance the function of these Borreliaceae-specific genes is largely unknown. However, many known Lyme disease virulence genes implicated in immune evasion and tissue adhesion originated in this evolutionary period. Taken together, these regularities point to the possibility that bleb and biofilm morphotypes might be important in the dissemination and persistence of B. burgdorferi inside the mammalian host. On the other hand, they prioritize the large pool of unstudied Borreliaceae-specific genes for functional characterization because this subset likely contains undiscovered Lyme disease pathogenesis genes.
And herein lies the age-old problem: unstudied Borreliaceae-specific genes that have not been functionally characterized, and undiscovered Lyme disease pathogenesis genes.  Everything else hinges on these unknowns.
This research is begging to be done, but has been avoided like the plague because of corrupt public health, run by one man doling out research grants whom has far too much power, and whom receives untracked, secret royalty payments.
COVID has shown the world what Lyme/MSIDS patients have been facing, only they have been in this hideous time-warp for over 40 years. Researchers are smart – they know they must cow-tow to the NIAID mafia overlord to get research funding, which means they must espouse the accepted narrative that Lyme is a simple nuisance cured with a couple weeks of a mono-therapy that hasn’t worked from the get-go.
Nobody seems to care but sick patients and a handful of ethical researchers who feverishly attempt to move a 40 year old needle that’s covered with an inch of rust.  When dissenting research finally does come out, it is retracted for flimsy reasons, in this case due to testing methods, but my educated guess is the research simply couldn’t stand because it revealed too much truth.  This is quite ironic considering the COVID ‘pandemic’ only occurred due to faulty testing insisted upon & patented by corrupt public health which quietly had to withdraw its EUA because it can’t distinguish between COVID and the regular flu.  Monopolizing medicine/disease is the CDC & FDA‘s MO and this includes testing, as virtually everything else spawns off of testing.  Control testing and you control the entire paradigm from research to drugs.
This diabolical monopoly then sets the ball rolling for the entire world, again demonstrating the frightening monopoly that must be broken.  Mainstream medicine, which is lazy, remains brain-washed and simply follows orders. And compliance is what corrupt public health is counting on.  Truth is crucified and dissenters are promptly tarred and feathered despite saving livesCensorship, bullying, firing and closing labs down, tossing out and manipulating data, fake science, and “disappearing” are efficiently deployed to silence any opposition.
Believe it or not, mainstream medicine still does not even believe Bb is pleomorphic.
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