It’s an all-too-common refrain nowadays, but antibiotic resistance remains one of the world’s most severe public health threats. Bacteria have developed resistance to nearly every antibiotic drug in our arsenal, and the Healthcare Infection Society has estimated that 10 million people will die annually from antibiotic-resistant bacteria by 2050.
Hoping to reverse these worrying trends, researchers from Oregon State University and Sarepta Therapeutics have developed a new method for killing antibiotic-resistant bacteria with drugs that we already have. The technique uses a molecule called a PPMO to directly target and suppress bacterial genes that confer resistance, which re-sensitizes bacteria to existing drugs. Initial experiments have only re-sensitized bacteria to a single drug (meropenem), but the general strategy can be extended to resistance mechanisms that deactivate many antibiotics at once; think “two birds, one stone.”
Therapies that “reverse” antibiotic resistance have been in use for decades, but most have been created via traditional drug discovery methods that are expensive and time-consuming. A PPMO, however, can be easily modified to target different resistance genes. This feature can bypass years of work because identifying these key genes is often easier, faster, and cheaper than building new molecules from scratch. Antibiotic resistance is growing so rapidly that having multiple ways to kill the same pathogen is becoming more and more valuable; think “one bug, many stones.”
PPMOs are nowhere near the clinic yet and will eventually confront resistance themselves, but they embody a promising strategy that aims to be as adaptable as the microbes they’re designed to kill.
Acknowledgments: Many thanks to Tracy Kambara, a graduate student in the Biological & Biomedical Sciences Ph.D. program at Harvard University, for providing her expertise and commentary on the topic.
Managing Correspondent: Christopher Gerry
Original Research: Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo – Journal of Antimicrobial Chemotherapy
Media Coverage: Scientists develop molecule that reverses antibiotic resistance – The Independent; Scientists just announced our best shot at ending antibiotic resistance to date – Science Alert
One thought on “Reversing Resistance: How to teach old antibiotics new tricks”
Mr. Dr. Christopher Gary, I found your work on bacterial resistance very interesting. Congratulations I am sending an essay on the second stage of the epidemiological curve, I would like to know your opinion as to why there is a descendant of the curve. Thanks in advance.
Please don’t call, i don’t speak english.
TEST: EPIDEMIC CURVE
01. After a number of replications, the replicative enzyme pathway becomes corrupted, blocking viral reproduction.
02. Biochemical Processes, Atoms and Molecules do not age or get tired; … They only suffer corruptions in their systems.
03. We will look for factors of corruption in the viral replicative pathways and we will solve much more than Covid-19.
SECOND PHASE OF THE EPIDEMIC CURVE
1. The peak of the curve depends on the population exposed to contagion; the larger the population, the higher the curve.
2. If the population remains exposed, the peak reaches a very high plateau.
3. If the exposed population is small, the curve will be flattened;
4. A question arises: why is there a descending segment of the curve if the exposed population is the same? ; … the virus got tired? … the population’s immunity has increased? this is not the case in the current COVID 19 virus.
5. One way of looking at the curve in its descending phase is through molecular biology;
6. Atoms and molecules do not age or wear out.
7. We work on the following essay:
– the virus has a limited number of replications.
– the enzyme system of this replication may suffer after the given number one
protein corruption preventing viral activity;
8. by studying the enzyme complex for DNA replication, we can see how pertinent this hypothesis is.
9. this hypothesis explains the descending epidemic curve since the exposed population remains the same.
10. viruses that do not have a corrupted system have passed to an endemic stage.
Some authors report that DNA errors are so frequent reaching a rate of 1 million per day, nothing happening because the cell has repair reactions immediately (each biochemical reaction is processed in a peak-second or billionth of a second).
When there are no repairs, malformations, metabolic errors and cancer occur.
If the virus reaches a rate of replication, or duplication of DNA, at risk for errors, it disappears; its virulence has ended and the epidemic curve enters its second phase of descent or fall.
If we ask why the repair enzymes did not work ?; … we will say that some protein was corrupted by messenger RNA representing a second error in the biochemistry of the virus.