Antibiotic resistance continues to be a growing problem in medicine. While overuse of antibiotics plays its role, the general fact of population and usage over time lends itself to the same outcome.
Some resistance can be mitigated by use of multi-drug systems that make it mathematically impossible for any one bacteria to become resistant to all of them at the same time, but even this isn’t fool-proof. Mis-timing and reliance on patients to always take their medicine at the right time every day isn’t something that can ultimately be controlled.
Because of this, scientists have turned their focus more to developing new kinds of antibiotics to replace the old ones and to better uncover the genetics involved in how antibiotic resistance forms.
Using Antibiotic Resistance To Research It
Research by a team at the Broad Institute of MIT and Harvard has come up with some concerning information in this regard. Their attention has been on how the mutational development of antibiotic resistance occurs and what concentrations of antibiotics are most likely to cause that development.
Using Mycobacterium smegmatis, the researchers applied low concentrations of specific antibiotics to see how it killed sensitive members of the colony while causing resistant mutations in small sections of the colonies.
The mutations were seen to have occurred within the ribosomal DNA (rDNA), whose primary function is building proteins from mRNA instructions. And, as expected, resistance was formed against the class of antibiotics being used, fluoroquinolones.
The Penny Drops
But there was a problem. When they tested other antibiotics on the bacteria, they found that the M. smegmatis had also developed resistance to nine other antibiotics, including several from completely unrelated classes to what was being tested. The bacteria had never even been exposed to those antibiotics in the first place.
From their testing, they found that the extra resistance didn’t appear to come from more mutations, since any further mutations besides those desired in regards to fluoroquinolones were controlled for. Meaning that it was those very same ribosomal mutations being tested that also gave resistance to unrelated antibiotics.
In addition, these ribosomal mutants showed better capabilities with two specific stresses unrelated to antibotics, namely high heat (54 degrees Celsius specifically) and stress on their cell membranes.
A Loss, But A Gain
Suggestions of decreased growth rate caused the scientists to look into whether these additional mutational effects reduced the fitness and capabilities of the bacteria. The answer is, to some extent, yes. The fitness cost of these extra abilities is a slower growth rate. But the is easily offset by the gains the bacteria obtains from the two kinds of stress resistance.
Overall, its fitness is likely improved rather than lowered. Meaning that it actually is more beneficial to the bacteria to aim for high-level multi-drug resistance mutations even with the growth cost for spreading itself out like that, due to the side benefits.
This new phenomenon requires much more research to understand, which the Broad Institute team will be conducting. Hopefully greater knowledge on how this multi-drug resistance works from ribosomal mutations will allow for the development of more targeted antibiotic drugs.
Photo CCs: A course of green cefalexin pills from Wikimedia Commons