Widely Used Antibiotics ↔ Mitochondrial Dysfunction

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Lola Lyme
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Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by Lola Lyme » Tue 24 Mar 2015 10:14

Widely Used Antibiotics Affect Mitochondria
From plants to mice and human cells, tetracyclines lead to mitochondrial dysfunction in model organisms.
March 12, 2015

The tetracycline-controlled promoter system is a widely used tool to conditionally switch gene transcription on or off in the presence of the eponymous antibiotic. Adding tetracyclines to eukaryotic cells leads to altered mitochondrial genome translation and cellular respiration defects across five widely used eukaryotic model systems..

Two years ago, study coauthor Johan Auwerx, an energy metabolism researcher at the École Polytechnique Fédérale in Lausanne, Switzerland, and his colleagues observed that the tetracycline class of antibiotics, which target mitochondrial translation, led to an imbalance between mitochondrial and nuclear protein translation in both worms and mammalian cell lines. Expanding on this observation, the researchers have now shown that even low concentrations of tetracyclines can inhibit mitochondrial function and lead to changes in both mitochondrial and nuclear protein expression. Across four commonly used human cell lines, as little as 1 microgram of the drug per milliliter resulted in a decrease in cellular respiration, signaling impaired mitochondrial activity. Treatment with amoxicillin, an antibiotic that does not target protein synthesis in the mitochondria, did not lead to these effects. Further, genome-wide expression data showed global repression of mitochondrial protein synthesis in the presence of the tetracycline doxycycline.

Given their results, the researchers cautioned against widespread tetracycline use in livestock because of the potential repercussions for neighboring plant life and human health. “This aspect of some antibiotics . . . has been overlooked,” said study coauthor Riekelt Houtkooper, a molecular biologist who studies metabolic aging at the Laboratory Genetic Metabolic Diseases of the Academic Medical Center in the Netherlands. “There is a lot of interest in antibiotic resistance and on the effects of antibiotics on the microbiome, but the effects on mitochondria is a whole new angle.”

“Our guts contain 10 times more bacteria than cells but the mitochondria are even more abundant than the bacteria in our guts,” Houtkooper continued. “We need more studies to show how the environment is affected by antibiotics.”

Nunnari agreed. “The pervasive use of any drug class, as in the case of tetracyclines, should always raise concerns about the more global consequences,” she said. “As basic scientists, we don’t think about the global consequences of the use of this drug class enough. This [study] will raise awareness.”
Read more Source: TheScientist

duncan
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Re: Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by duncan » Sun 29 Mar 2015 18:20

I've been meaning to say thank you, Lola Lyme, for posting this.

It is a bit alarming when you realize most Lyme patients have been prescribed tretracyclines at one time or another, some of us for protracted periods. I'm on a cocktail that includes mino right now.

Even when we think we've a good and reliable set of directions to get out of this dangerous terrain, it would appear we have managed to wander into the middle of a minefield.

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ChronicLyme19
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Re: Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by ChronicLyme19 » Sun 29 Mar 2015 22:07

Some tetracyclines are also prescribed long term for acne as well.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

Lorima
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Re: Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by Lorima » Mon 30 Mar 2015 3:07

Here's a link to the full text of the paper:
http://www.sciencedirect.com/science/ar ... 1?via=ihub

I think the point they're making is reasonable, that one should consider the environmental effects of spreading tetracyclines around excessively. Lots of organisms might have organelles less tolerant to them than mammals.

It was less alarming that I feared, with regard to mammals and LD treatment, when I looked at the mouse data. I don't know enough about variations in normal mitochondrial function between mouse strains, or different humans, to know if the differences they observed are likely to be clinically significant. But they used very large doses of doxy: 50 mg/kg/day (which would be 2500 mg/day in a 50 kg person, while a Lyme patient on IDSA treatment would be taking 200 mg/day, and on ILADS treatment maybe 400 mg/day, or at most 600 mg/day; needless to say, a BIG difference). They also tried 500 mg/kg/day (a huge dose: 25 grams/day in a 50 kg person!).

I rather doubt they would see any effect at a normally used dose.

The theoretical possibility that it's a problem relevant to LD treatment still exists; it's just not something to panic about.
"I have to understand the world, you see."
Richard Feynman

TDP
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Re: Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by TDP » Thu 9 Apr 2015 22:35

At the dose levels used to treat humans, there my be more potential benefit than harm from the effects on mitochondria. Very recent work by a group at the Breakthrough Breast Cancer Unit at Manchester U. has just been published in Oncotarget http://www.impactjournals.com/oncotarge ... 5B%5D=6139

Doxycyclin was one of a number of antibiotics shown to have significant inhibitory effects in vitro on a range of tumour cell lines. The head of the unit, Prof Michael Lisanti, has been studying the role of mitochondria in cancer growth and metastasis.

His group have shown that at least some cancer cells 'hijack' energy production for neighbouring cells such as fibroblasts. Mitochondria were once bacteria, so are susceptible to inhibition by antibiotics that target ribosomes (small structures that assemble amino acids into protein as they move along mRNA strands).

The study also showed little reduction in growth of normal (non-transformed) cell lines even at concentrations 10 times higher than that which significantly inhibited the tumour cells.

Definitely worth watching developments, especially because as well as breast cancer, two other potential targets are pancreatic cancer and lung cancer; both of which have very poor survival rates.

It is also noted in the paper that doxycyclin is officially prescribed for periods of 4 - 6 months or longer for certain infections. Other potential benefits are mentioned in the discussion.

You might want to look at the authors' affiliations, especially that of Camilla Lisanti. I have never before seen a paper with an author aged 8!

lou
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Re: Widely Used Antibiotics ↔ Mitochondrial Dysfunction

Post by lou » Sun 19 Apr 2015 2:02

Thank you Lorima for pointing out the dosages, which definitely puts a different slant on it.

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