Research efforts to find safer alternative delivery methods for neomycin, a common topical antibiotic that is never dispensed topically, are ongoing. In so doing, they hope to reduce serious adverse effects and tackle the increasing threat of antibiotic resistance. The antibiotic neomycin was first discovered by scientists in the 1940s. Since then, it’s been quite successful in preventing infections, particularly in over-the-counter ointments such as Neosporin. Using neomycin as an injection to cure systemic infections endangers public health. These often life-changing consequences can be deafness, kidney damage, and neurological impairment.
The research team aims to make neomycin a safer option for injections by understanding how certain cells interact with the antibiotic. They think they can mitigate the drug’s negative impacts. They aim to achieve this by targeting certain proteins that govern how lipids migrate around cell membranes.
Understanding Neomycin and Its Risks
Neomycin, an important and effective topical antibiotic long used worldwide to prevent infection in a variety of surgical and medical contexts. This is because its effectiveness comes from its ability to target and kill bacteria. While there may be other acceptable uses for this drug, its use as an injectable treatment is extremely dangerous. What they found Neomycin carries a dangerous risk of causing deafness and irreversible kidney damage. This peril arises mostly due to its action on cells whose ATP9A and ATP9B proteins are expressed in low amounts.
These proteins are incredibly important as they are responsible for maintaining the asymmetry of the cell membrane. In kidney cells these proteins are less active. As a consequence, another lipid, PI4P, appears on the outer membrane. This exposure shifts the balance of these cells, causing their sensitivity to neomycin distinguished and sensitive cells to undergo adverse effects.
“It is essential to understand the mechanisms of antibiotic resistance in order to develop more effective drugs.” – Todd Graham
The Role of PI4P and P4-ATPases
Studies have demonstrated that P4-ATPases represent key proteins responsible for lipid transport. They act to control levels of PI4P in cellular membranes. Typically PI4P exists within the cytosolic leaflet of the plasma membrane. Mutations in proteins like Neo1 can have catastrophic effects. Considering that Neo1 functions closely with ATP9A as well as ATP9B, this defect can lead PI4P to translocate to the outer monolayer.
This change can make kidney cells more susceptible to the effects of neomycin. Now, researchers are hoping to figure out just what PI4P is doing in membranes. With this knowledge, they want to develop approaches that shield human cells from the harmful effects of neomycin.
The research team looks forward to testing different methods to knock PI4P out from the outer membrane of kidney cells. If adopted successfully, this would make a substantial dent in the grim adverse impacts that have been reported with neomycin injections.
Future Directions in Antibiotic Research
Researchers aren’t solely focusing their efforts on neomycin. Finally, they would like to investigate how PI4P affects human cell susceptibility to other antibiotics. Characterizing these dynamics might inform more general applications for the treatment of antibiotics as well as the management of antibiotic resistance.
The impact of this research goes far beyond just making neomycin safer for intramuscular injection. In so doing, it would open the door for more advanced approaches to antibiotic therapy that spur less resistance and better serve patients.
Today, the scientific community finds themselves in a deepening war against antibiotic resistance. This research holds tremendous promise for the development of more effective and safer drugs that can combat life-threatening infections without the side effects associated with some existing therapies.