The nationwide experiment will initially include around 100,000 volunteers.
Bacteria-killing antibiotics might also damage a person’s tissues.
July 3, 2013|
WIKIMEDIA, SHORELANDERIn addition to the growing threat of antibiotic-resistant bugs, there may be another reason doctors should refrain from freely prescribing antibiotics. According to a paper published online today (July 3) in Science Translational Medicine, certain antibiotics cause mammalian mitochondria to fail, which in turn leads to tissue damage.
“What the authors are suggesting is that in addition to the bactericidal properties of antibiotics, they also affect . . . the mitochondria,” said Navdeep Chandel, a professor of medicine and cellular biology at Northwestern University in Chicago, who was not involved in the work. “And what’s fascinating about that is that mitochondria are thought to be [ancient] bacteria themselves.”
Indeed, mitochondria, the organelles responsible for energy production in the cell, have bacteria-like DNA and other molecules, suggesting that mitochondria are the product of an ancient endosymbiotic event, in which a bacterium was engulfed by another cell. The important implication of this, said Ronald DePinho, president of the MD Anderson Cancer Centre in Houston, Texas, who also did not participate in the research, is that “drugs targeted to [bacterial] physiology might also impinge on mitochondrial biology.”
This concern led Jim Collins, a professor of biomedical engineering at Boston University, to study the effect of antibiotics of mitochondria. His team had previously reported that antibiotics cause a surge in the production of reactive oxygen species (ROS)—highly reactive and potentially damaging molecules—inside bacteria, which may be part of the drugs’ bacteria-killing mechanism. Collins and his team therefore asked whether antibiotics also lead to an increase in ROS production in mammalian mitochondria.
The team treated human cell lines from a variety of tissues with three different types of bactericidal antibiotic: ciprofloxacin, ampicillin, and kanamycin. “We found that at clinical levels each of the antibiotics generated ROS,” said Collins, “and we showed that they do this in part by disrupting mitochondrial function.” On the other hand, an antibiotic called tetracycline, which does not kill bacteria but merely prevents their growth, did not cause an increase in ROS.
The cells given the bactericidal antibiotics also exhibited oxidative stress—the damage caused by ROS binding and oxidizing various cellular components. Indeed, there were signs of DNA, protein, and lipid damage, said Collins. And when the same three antibiotics were given to mice, increased ROS levels and oxidative damage to tissues was also apparent.
For the average person who might be prescribed a short course of antibiotics, DePinho reckoned there would probably be nothing to worry about. “We have very robust DNA damage repair mechanisms that in the short term may attenuate any clinical impact,” he said. However, he added, “it could be different in the context of chronic administration of antibiotics.”
To see if they could prevent such damage, Collins and his colleagues treated the human cells and the mice with an antioxidant called N-acetyl-L-cysteine (NAC) in addition to the antibiotics. The NAC mitigated the antibiotic-induced ROS increase and oxidative stress, but importantly it didn’t affect the antibiotics’ bactericidal activities. Mice given a urinary tract infection, then treated with an antibiotic, cleared the bacteria just as effectively whether or not they were given NAC along with an antibiotic treatment.
The lack of NAC’s effect on the bactericidal ability of the antibiotics “is likely specific to this antioxidant,” said Collins, because other antioxidants that his group has since tested did reduce antibiotic activity. Collins speculated that NAC might not penetrate the bacteria themselves, and reduce only the mitochondrial-derived ROS, thereby protecting the cells but not the bacteria. But, Collins said, “more work is needed to find out what would be the effective and appropriate antioxidant to take.”
For now the paper’s immediate message, said Collins, is that “coupled with the concerns about drug-resistance. . . one should only use antibiotics when you really need antibiotics.”
S. Kalghatgi et al., “Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells,” Science Translational Medicine, 5: 192ra85, 2013.
July 7, 2013
July 8, 2013
Thank you very much for publishing this article! I also thank Dr. Collins and all of the other researchers who worked with him on this project. It is WONDERFUL that the adverse effects associated with antibiotics are being looked at. They are not insignificant and it is a move in the right direction to scientifically examine the mechanisms by which antibiotics can hurt people.
At the age of 32 I was "floxed," a term for those who suffer from the array of ailments associated with fluoroquinolone antibiotics, Cipro, Levaquin and Avelox are the most popular fluoroquinolone antibiotics on the market at the moment. My story, as well as the stories of several others, can be found on my web site, www.floxiehope.com.
Because of the delay in onset of adverse reactions to fluoroquinolones, and because the damage done by fluoroquinolones is so severe that it seems unthinkable that an antibiotic could cause the damage that fluoroquinolnes do, the risk/danger associated with these drugs is drastically underestimated. What if fluoroquinolones and the mitochondrial damage that they cause are linked to fibromyalgia, chronic lyme disease, chronic fatigue syndrome / Myalgic Encephalomyelitis, Desert War Syndrome, anxiety, depression, suicide, plantar fascitis, autism, leaky gut syndrome, rheumatoid arthritis, M.S., Lupus, carpal tunnel syndrome, etc.? Many of those are complex diseases with multiple causes, but many cases can likely be traced back to fluoroquinolone use.
I don't want to be critical, but I struggle to understand why these antibiotics were all studied together. A simple look through wikipedia or askapatient.com will clearly show that fluoroquinolones have much more severe adverse effects than other antibiotics. To lump them all together is throwing the baby out with the bathwater a bit.
To anyone who takes the time to read my story in FloxieHope, THANK YOU! It is really important that the stories of the victims of these drugs be listened to and that something be done to prevent further victimization of innocent people.
August 2, 2013
In additon to the disruption of normal ROS signalling pathways mentioned in this paper many antibiotics have two other deleterious effects in human cells. They decrease respiratory competence and shift cell populations to aerobic glycolysis (the Warburg effect) resulting in localized lactic acidosis and a microenviroment favorable to tumor formation, tissue invasion and metastasis. In addition increased poduction of ROS is mutagenic to both nDNA and mtDNA destabilizing both genomes, decreasing mitochondrial survellance and clearing of tumorigenic karyotypes in the nucleus by the intrinsic apoptotic pathway, both hallmark features of cancer. I suggest (in agreement with many other investigators) that such antibiotics are carcinogenic and thus the findings reported here are very clinically relevant especially when administered for chronic infection. We need to find alternative antimicrobial therapies for non life threatening infections that do not harm these patients.