Jason Carlyon, Director of Studies. (Credit: Virginia Commonwealth University)
Various microbial rebounds threaten human health. So far, antibiotics greatly benefit from bacteria. however Sleeping on bearings is not in place because creatures can adapt to drugs. Maintaining leadership depends on trying to find new ways fight.
Virginia Commonwealth University researchers and their collaborators from four other US-based universities have contributed to maintaining leadership. In the disclosed publications, some antidepressants inhibit the growth of at least four intracellular parasitess.
In human cell lines in the tube and even in one microbial type in vivo, the mice examined the antimicrobial activity of the tricyclic antidepressant desipramine. They also discussed the mechanisms individual microbial species and their developmental stages.
They got excellent bacterial results in the tests against bacteriaand Anaplasma phagocytophilum induces human granulocytic anaplasmosis, which may end up in elderly patients with weaker immune function and have no antibiotic intervention death. The infection spreads with ticks, and although the disease is rarely known as other stomach-related diseases, it can also be transmitted to the Czech Republic.
parasite Anaplasma p. it contaminates white blood cells. (CC BY-SA 3.0)
Likewise, desipramine well rotated with the microorganism Coxiella burnetii producer Fever Q. However, rare zoonosis is common in domesticated and domesticated animals. Mostly it is obtained from animals by inhaling contaminated dust or not swallowingwrought animal products. As a result of this very low dose of infectionky and Persianse environment has been tested on andMarine soldiers within the framework of the Biological Weapons Development Program. Q is no exotic voice in Europethem unprecedented issues proves 4000 cases recorded between years 2007 – 2010 in the Netherlands.
Only the latterofChlamilleydiim because the experiments with them did not go so well. Chlamydia trachomatis which causes nruling withxinfectious urogenital infections. it was statistically significant inhibitedbut the blocking speed did not reach biological importance. The test was betterand a slower growing pathogen Chlamydia pneumoniae specialized respiratory tract infections system. U his treatment of illusions had partially suppressed reproduction.
The lower graph shows the number of copies of the genetic information Anaplasma p. the blood of infected mice depending on the infection. The blue mark belongs to the control group of animals and the red group to which desipramine was given. Infection in the group under the influence of antidepressant did not come at all. The upper chart shows almost the same. Only the lack of enzyme function is innate in ASM – / – mice (red marking), which makes them resistant. Similarly, in humans, we know the hereditary Niemann-Pick disease caused by ASM deficiency. So they too have to be immune to infection. (Credit: DOI: 10.26508 / lsa.201800292, CC BY 4.0)
Significant antimicrobial properties observed indicate that they may have antidepressantsand to replace antibiotics with anaplasmOhZY in the end Q fever. although The tested pathogens are generally completely sensitive to suitable antibioticsé and acute Infection, if the situation so requires, usually solves its short-term management, records any willingness to conduct clinical trials on several assumptions in the future. In particular, desipramine does not directly damage the parasite but affects the fate of cholesterol in a host cell that does not control the pathogen. For this reason, it is probably excluded that he would have accepted an easily accessible adaptation mechanism against him.
In addition, any action to reduce classical antibiotic consumption limits the selection of resistant bacteria. In addition, the narrow spectrum substance does not affect the patient's natural and beneficial microbes. Both properties would be particularly useful in the treatment of chronic infections. Because of the different lifestyles of beginners, it can sometimes be difficult dispose of the human body. The presence of an antibiotic prevents proliferation, but bacteria with low metabolic activity do not kill. Hiding internal cells with loss of ability apoptosis Intruders protect against the immune system. Then they can live in the body for quite a long time and under favorable conditions to start a new attack. For example, when fever Q goes into chronic form, treatment requires at least 18 months of antibiotic intake.
As already explained, noé Therapeutic despair does not force clinical trials and desipramine signs expand. Nor is it anything simple and does not see any financial benefit for pharmaceutical companies. On the other hand, the long-term use of the registered drug, the taking of evidence and the administration itself all experimental compound should go left behind.
The authors have not yet reviewed all the representatives suspects hit black. Whether antidepressant Prevent parasites Ehrlichia chaffeensis, Toxoplasma gondii and Brucella abortus waiting for response. Partial suppression detected by P cannot be eliminated Chlamydia pneumoniae. It is certainly necessary combination with common antibiotic. It certainly adds success treatment and reduces the likelihood of developing resistance.
Other authorized medicines with the same effect
Although intracellular parasites living in host cells are bacteria, their strategy resembles mannersismy viruses. To create a new generation, they must definitely get into the cell and enslave it his put to account. produce Unlike viruses, proteins lead from their own devices. What they need to steal (ATP) comes from the mitochondria that they lost during coevolution. Although they have tools to ensure a lot of independence in the synthesis of building materialsat, they seem to collect actively to build a cholesterol-separating diaper it is from cytoplasm host cells and suffer from anxiety if this process is disturbed.
The graph shows an increase in chlamydia in cell culture. C. trachomatis is slightly blocked (black beam) against control (white bar). U C. pneumoniae blocking is clearer. (Credit: DOI: 10.26508 / lsa.201800292, CC BY 4.0)
In a cell, cholesterol can come from within (synthesis) or from outside. In the second case, what is decisive From the point of view of desipramine activity, cholesterol retains cellular receptors in the form of LDL particles. Then the trapped lipid is transported cell organelles lysosome, where it passes hydrolysis. This host cell is chemically modified. The bacterium then promises lysozyme to remove the finished material.
Hydrolysis of cholesterol v lysosomitoiminnan an old protein attached to the organoleptic membrane of the cell; acidicFingomyelinase (ASM). It is an ASM blocker that interrupts the route and closes the parasite with a cholesterol tap. The microbial disorder wipes the biological expression of a broader group of substances, including desipramine. They have the abbreviated name FIASMA (Functional Inhibitors of Acid Sphingomyelinase).
The FIASMA ASM inhibition method is more detailed. Neutral FIASMAs penetrate the acidic environment of lysosome and form cations that make lysosome organelles they can't escape. That's why lysoziyhe will accumulate and Lipophilic interactions adhere to the membrane negatively charged under the membrane. Because they have a positive charge, they target the opposite mark of the membrane and thus isolate the binding force of ASM to the substrate. So far, anchored ASM loses the soil and the subsequent release of protein destroys proteolytic events.
The principle of blocking means that FIASMAs may not be strict configuration such as other inhibitors. UPjust enough structure was a weak lipoFand basic features. because there is many of these substancesand approved medicines, but they are not all as effective. Z registered medicines include all tricyclic and SSRI antidepressants antipsychotics, antihistamines, antihypertensives and others. In short, there is a lot to choose from and maybe between them hiding the future Assistant for the management of several selected infectious diseases.
DOI: 10.26508 / lsa.201800292