Archive for the ‘research’ Category

How Does the Lyme Spirochete Control OspC?

https://journals.asm.org/doi/10.1128/jb.00440-22

Gac Is a Transcriptional Repressor of the Lyme Disease Spirochete’s OspC Virulence-Associated Surface Protein

Authors: Tatiana N. Castro-Padovani, Timothy C. Saylor, Olivia T. Husted, Andrew C. Krusenstjerna, Nerina Jusufovic, Brian Stevenson https://orcid.org/0000-0002-2406-4776 brian.stevenson@uky.eduAUTHORS INFO & AFFILIATIONS
DOI: https://doi.org/10.1128/jb.00440-22
ABSTRACT

The OspC outer-surface lipoprotein is essential for the Lyme disease spirochete’s initial phase of vertebrate infection. Bacteria within the midguts of unfed ticks do not express OspC but produce high levels when ticks begin to ingest blood. Lyme disease spirochetes cease production of OspC within 1 to 2 weeks of vertebrate infection, and bacteria that fail to downregulate OspC are cleared by host antibodies. Thus, tight regulation of OspC levels is critical for survival of Lyme borreliae and, therefore, an attractive target for development of novel treatment strategies. Previous studies determined that a DNA region 5′ of the ospC promoter, the ospC operator, is required for control of OspC production. Hypothesizing that the ospC operator may bind a regulatory factor, DNA affinity pulldown was performed and identified binding by the Gac protein. Gac is encoded by the C-terminal domain of the gyrA open reading frame from an internal promoter, ribosome-binding site, and initiation codon. Our analyses determined that Gac exhibits a greater affinity for ospC operator and promoter DNAs than for other tested borrelial sequences. In vitro and in vivo analyses demonstrated that Gac is a transcriptional repressor of ospC. These results constitute a substantial advance to our understanding of the mechanisms by which the Lyme disease spirochete controls production of OspC.
IMPORTANCE
Borrelia burgdorferi sensu lato requires its surface-exposed OspC protein in order to establish infection in humans and other vertebrate hosts. Bacteria that either do not produce OspC during transmission or fail to repress OspC after infection is established are rapidly cleared by the host. Herein, we identified a borrelial protein, Gac, that exhibits preferential affinity to the ospC promoter and 5′ adjacent DNA. A combination of biochemical analyses and investigations of genetically manipulated bacteria demonstrated that Gac is a transcriptional repressor of ospC. This is a substantial advance toward understanding how the Lyme disease spirochete controls production of the essential OspC virulence factor and identifies a novel target for preventative and curative therapies.

Category:

Lyme, research

Study: Lyme Forms May Affect Persistence

https://www.mdpi.com/1422-0067/24/6/5594

Pleomorphic Variants of Borreliella (syn. Borrelia) burgdorferi Express Evolutionary Distinct Transcriptomes

by Nina Čorak1, Sirli Anniko2,3, Christina Daschkin-Steinborn2, Viktoria Krey2,4, Sara Koska1, Momir Futo1,5,6, Tin Široki5, Innokenty Woichansky 2, Luka Opašić1, Domagoj Kifer7, Anja Tušar1, Horst-Günter Maxeiner2,8, Mirjana Domazet-Lošo5, Carsten Nicolaus2 and Tomislav Domazet-Lošo1,6,*
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. 2023, 24(6), 5594; https://doi.org/10.3390/ijms24065594
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)

Abstract

Borreliella (syn. Borrelia) burgdorferi 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.
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**Comment**
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 lives.  Censorship, 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.

Category:

Lyme, research, Testing

CDC: Babesiosis Cases Rise Sharply in Northeastern US

https://www.lymedisease.org/cdc-babesiosis-rises-sharply/

CDC: Babesiosis cases rise sharply in Northeastern US

Cases of the tick-borne disease babesiosis increased sharply in some Northeastern states between 2011 and 2019, according to a new CDC report.

The agency says the infection is now endemic in three new states: Maine, New Hampshire, and Vermont.

Previously, the disease was considered endemic only in Connecticut, Massachusetts, Minnesota, New Jersey, New York, Rhode Island and Wisconsin.

Humans typically acquire babesiosis from deer ticks, whose bites can transmit Babesia parasites that infect red blood cells.

It can also be transmitted via blood transfusion or during pregnancy, from an infected mother to her unborn child.

For more information:

CDC report

New York Times

ABC News

For more:

Category:

Babesia, research

IV Antibiotics Helpful For PTLDS

https://danielcameronmd.com/intravenous-antibiotics-helpful-for-ptlds/

INTRAVENOUS ANTIBIOTICS HELPFUL FOR PTLDS

antibiotics-ptlds

Post Treatment Lyme Disease Syndrome (PTLDS) can develop in patients even after receiving antibiotic treatment for Lyme disease. Although the exact cause of PTLDS is unknown, it could be due to a persistent infection. PTLDS is characterized by fatigue, pain and cognitive difficulties.

By 

In their study “Efficacy and safety of antibiotic therapy for post-Lyme disease? A systematic review and network meta-analysis,” Zhang and colleagues described a meta-analysis review of four Randomized Clinical Trials (RCT) addressing Post-Treatment Lyme Disease Syndrome.¹

The four randomized controlled trials included 485 subjects who met the following inclusion criteria:

  • Randomized controlled trials
  • Patients with Post-Lyme Disease Syndrome which has persisted for at least 6 months after treatment of the initial infection and who tested positive by IgG Western blot
  • Patients aged 18 years and above
  • Number of cases providing valid data to measure outcomes
  • Studies that the control group used placebo, while the observation group took the antibiotic

Their meta-analysis showed that ceftriaxone had better results than placebo on FSS. “FSS-11 is the most widely used scale to measure the fatigue severity of the subjects,” wrote Zhang et al.

“Ceftriaxone treatment may be the best choice for antibiotic treatment of PTLD, which provides useful guidance for antibiotic treatment of PTLD in the future.”

The systemic meta-analysis concluded that intravenous ceftriaxone may be the best choice for treating Post-Treatment Lyme Disease Syndrome.

An NIH-sponsored clinical trial demonstrated that intravenous ceftriaxone therapy improved patients’ cognitive function in the short term, according to Fallon.² There were no trials addressing pain.

The authors were not able to show significant gains in the Beck Depression Inventory (BDI), Mental Health Scale and Physical Functioning Scales. Neither were they able to show significant gains with oral doxycycline.

Zhang et al. acknowledged several limitations to their study. “The number of RCTs is small; The duration and dose of treatment in these RCTs are not uniform; The follow-up time of various RCTs is different to some extent.”

Author’s Note: I have been reluctant to recognize the term PTLDS until there is a reliable test to exclude a persistent infection. This systemic meta-analysis validated my concerns that PTLDS may be the result of a persistent infection.

Related Articles:

Podcast: Post-Treatment Lyme Disease Syndrome Cases

4 Distinct Post-Treatment Lyme Disease Syndromes?

Number of Post-Treatment Lyme Disease Syndrome cases expected to soar

References:
  1. Zhang X, Jiang Y, Chen Y, et al. Efficacy and safety of antibiotic therapy for post-Lyme disease? A systematic review and network meta-analysis. BMC Infect Dis. Jan 12 2023;23(1):22. doi:10.1186/s12879-023-07989-4
  2. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. Mar 25 2008;70(13):992-1003. doi:10.1212/01.WNL.0000284604.61160.2d

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For more:

Please note that the FDA’s continued attack on supplements and medications it deems a threat could very well impact Lyme/MSIDS patients.

Category:

Activism, Lyme, research, Treatment

The Real Reason the FDA is Attacking NAC

https://wmcresearch.substack.com/p/friday-hope-n-acetyl-cysteine-nac

Friday Hope: N-Acetyl Cysteine (NAC) Revisited: Taming the ROS Storm

The Oxygen Radical Removal Specialist

Walter M Chesnut

March 17, 2023
Article Excerpts:

We have long known of the cytokine and bradykinin storms associated with the severity and mortality of COVID-19. However, as my research began to reveal, I believe these are secondary to the main culprit in COVID-19 and Spike Protein pathology: The Reactive Oxygen Species (ROS) Storm.

Indeed, this has been hypothesized by others.

Previous studies highlighted the significance of a cytokine storm to the severity of SARS-CoV-2 infection, and more recently, the possibility of another storm, the bradykinin one, also contributing to the widespread tissue damage observed in some COVID-19 patients, involving those with hypertension comorbidity. Under these unprecedented conditions, there is yet, another equally relevant, still overlooked, storm on the forecast for hypertension: the reactive oxygen species (ROS) storm.

This is where NAC enters the picture.

It acts directly as a scavenger of free radicals, especially oxygen radicals. NAC is a powerful antioxidant. It is also recommended as a potential treatment option for different disorders resulted from generation of free oxygen radicals.

A Review on Various Uses of N-Acetyl Cysteine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507

N-Acetylcysteine to Combat COVID-19: An Evidence Review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649937/

NAC has the potential to be one of our most effective weapons against SARS-CoV-2 and its Spike Protein.

(See link for article)

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**Comment**

If the FDA attacks a supplement or medication, rest assured, there’s a nefarious reason they don’t want you to have it.

For more:

Supplements stand in the way of this medical monopoly our corrupt government is so determined to own.

Category:

Activism, research, Supplements, Viruses