Researchers have developed sensors that can determine how well an antibiotic is working by measuring the concentration of active antibodies in the blood and this could help in developing personalized treatments for infections.
Antibiotics we use to fight off infections work in various ways, some blocking essential bacterial enzymes and protein synthesis and others inhibiting bacteria from turning glucose into energy. But the most powerful class of antibiotic agents, such as penicillin and cephalosporin, attack bacterial cell walls and membranes, working like termites eating away at the wooden walls, until the bacteria eventually collapse.
These antibiotics are so chosen to attack only the bacteria but not other healthy cells in your body. However, various other molecules, such as serum proteins, in the blood can bind to these antibiotics and prevent them from tearing down the cell walls.
When this happens, a drug that is bound to blood serum is no longer available to target the harmful organisms and becomes anti-bacterially inactive. So there will be less number of antibiotic molecules left in the blood to attack bacterial cell walls.
Measuring active free drug molecules in the body which are available to attack bacteria and those that have become anti-bacterially inactive is very important to understand the efficacy of a drug and to identify the correct and safe patient dosage.
Now researchers from the Institute of Molecular Bioscience affiliated to the University of Queensland and the London Centre for Nanotechnology (LCN) at University College London, have designed extremely small nanoscale sensors that can determine how effective an antibiotic is by rapidly calculating the concentration of active antibodies in a blood sample.
“These sensors, just one billionth of a metre in size, detect the bending that occurs in a cell wall when it is under attack by antibiotics,” says one of the researchers Professor Matt Cooper from The University of Queensland. “This enables us to measure how many antibiotic molecules are free in the blood to attack bacteria and treat the infection based upon how much force they exert onto the wall.”
The research, published in the journal Nature Nanotechnology, is the first time nanomechanics have ever been used to compare the drug resistance of a newer antibiotic against an older antibiotic and to provide guidance and understanding as to the therapeutic doses needed in the whole blood.
The researchers tested the method on vancomycin, a drug-of-last-resort used to treat multi-drug resistant infections such as Methicillin-resistant Staphylococcus aureus, and oritavacin, a new antibiotic yet-to-be-approved by FDA but is believed to show promise in combating vancomycin-resistant bacteria, to understand how variations in strong and weak competing ligands in blood can be used to determine dosages in drug therapies.
Since the amount of free antibiotics varies from person to person, the research also helps to make out the specific tailored dosage required to each individual to immediately treat an infection. This is a great advance towards personalized medicine to identify the best antibiotic dosages for different individuals and different infections.
This research, which uses nanomechanical cantilevers as surface-stress sensors to study how surface receptors on bacterial cell walls respond to different antibiotics in the presence of competing ligands in solution, also gives insights into how stronger antibiotics can be designed to fight off superbugs.
Superbugs are the bacteria that have developed resistance to multiple antibiotics largely via genetic mutations. They survive antibiotics by inactivating or modifying the drug molecules, altering target sites or metabolic pathways and more importantly, by having stronger bacterial cell walls that decrease permeability to the drug molecules and reducing drug accumulation around the cell surface.
“Understanding the way antibiotics use physical force against bacteria could also provide researchers with a new angle on the design of better drugs to fight superbugs, which often have thicker, stronger cell walls,” Professor Cooper said.
With superbugs infecting 2 million people and killing 23,000 every year in the US alone, this is perhaps just the right kind of research needed at this stage to understand how more potent antibiotics can be designed to identify, de-activate and destroy drug-resistant bacteria.