Recently it was reported that previous findings which indicate an existence of a general mechanism by which antibiotics kill bacteria could be wrong.
In 2007 researchers discovered that there might be "A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics". Scientists thought they found a discrepancy in classifying antibiotics into categories by their mechanism of action and that rather they shared one common way of killing bacteria.
All antibiotics elicited an increase in "production of highly deleterious hydroxyl radicals in Gram-negative and Gram-positive bacteria which ultimately contribute to cell death" and that "bacteriostatic drugs do not produce hydroxyl radicals". Thus, researchers concluded, "all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response".Now, of course we know that reactive oxygen species (ROS) are nothing to be scoffed at. Any chemist will tell you that having a molecule floating around with an unpaired electron in its outer shell is one of the most dangerous situations a stable local environment can find oneself in. First contact will be the last contact: ROS will bind to its first victim molecule and disrupt the functionality of said molecule. Add several of those angry scavengers and you are certainly in trouble.
Of course, not all is black and white. Some believe that free radicals and ROS under certain conditions can be beneficial to the organism and its longevity. Nothing is yet certain, but the field is certainly not stuck in a blissful state of complete understanding.
Returning to the issue at hand, all would seem at least somewhat logical that by inducing hydroxyl radical production antibiotics clearly contribute to them destroying bacteria. However an aforementioned study in Science refutes this notion.
Researchers claim that they
"found no correlation between an individual cell's probability of survival in the presence of antibiotic and its level of ROS".By using a compound, thiourea, an "ROS quencher" they
"protected cells from antibiotics present at low concentrations, but the effect was observed under anaerobic conditions as well".Since ROS are produced by aerobic respiration, the ability of an ROS quencher to protect bacteria from antibiotics in anaerobic conditions in which ROS cannot be produced indicates that ROS cannot be the deciding factor of bactericidal action.
To be even more sure, they marked cells with a fluorescent tag which showed ROS, separated those cells with highest amount of fluorescence (therefore, highest amount of ROS) from the lowest ones and both populations suffered equivalent cell death upon being bathed in antibiotics.
So the researchers concluded that
"There was essentially no difference in survival of bacteria treated with various antibiotics under aerobic or anaerobic conditions" and thus "this suggests that ROS do not play a role in killing of bacterial pathogens by antibiotics".With this notion of general mechanism by which antibacterials operate severely damaged, we return to viewing each class as different. Some inhibit the synthesis of cell walls (beta-lactams like penicillin), others dampen the synthesis of nucleic acids (fluoroquinolones), proteins (tetracyclines), act as anti-metabolites (folate pathway inhibitors: sulfonamides) or disrupt membrane function (cyclic lipopeptides: daptomycin).
There is yet much to be said about antibiotics, most pressingly their overuse. Ever increasing bacterial resistance to antibiotics is one of the most pressing matters to be solved. This is exemplified by the recent "nightmare bacteria" which is spreading across US hospitals and is resistant to most powerful antibiotics. More importantly, it kills half of those it infects. Dr. Marc Siegel vocalizes the seriousness of this situation: ""To see bacteria that are resistant is worrisome, because this group of bacteria are very common. The more you use an antibiotic, the more resistance is going to emerge. This is an indictment of the overuse of this class of antibiotic [carbapenems]."
There is a growing awareness and desire to cut back on needless antibiotic usage among an increasing number of people. A piece in The Atlantic has one such anti-antibiotic enthusiast who may just be going a bit too far ("our 14-year-old son had never taken antibiotics"), but at least it shows an increase in understanding that an overly runny nose or a mild fever does not require an onslaught of broad-spectrum antibiotics.
One especially crucial point was made:
"Antibiotics are unnecessary for colds or bronchitis, even when they last longer than two weeks. Colds and bronchitis often take more than two weeks to resolve, so if there are no signs of pneumonia, then antibiotics can be withheld safely."Antibiotics are used each and every day and everyone has a general understanding of what they do. In spite of this they remain elusive and still baffle some researchers. They are useful and crucial for keeping the society healthy, however our need to shorten the duration of even the mildest of discomforts can lead to our inability to protect ourselves when the real enemy emerges.
References:
1. I. Keren, Y. Wu, J. Inocencio, L. R. Mulcahy, K. Lewis. Killing by Bactericidal Antibiotics Does Not Depend on Reactive Oxygen Species. Science, 2013; 339 (6124): 1213 DOI: 10.1126/science.1232688
2. Michael A. Kohanski, Daniel J. Dwyer, Boris Hayete, Carolyn A. Lawrence, James J. Collins. A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics. Cell - 7 September 2007 (Vol. 130, Issue 5, pp. 797-810). doi:10.1016/j.cell.2007.06.049
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