Drug-resistant bacteria may still be killed if antibiotics "push" hard enough, researchers have found.
In a study published in the journal Scientific Reports, researchers led by a team from University College London detailed a promising new means by which antibiotic resistance can be overcome, offering scientists the opportunity to design drugs to be more effective.
How Antibiotics Work
"Antibiotics work in different ways, but they all need to bind to bacterial cells in order to kill them," said Joseph Ndieyira, the study's lead author.
He likened antibiotics and bacteria to keys and locks. Antibiotics have "keys" that fit into "locks" located on bacterial surfaces. When a key fits into a lock, antibiotics are able to latch onto bacteria, killing it. When bacteria develops drug resistance then, locks are basically changed. This means the keys won't fit anymore, rendering antibiotics ineffective. However, the researchers discovered that certain antibiotics have the ability to strong-arm locks, forcing themselves unto bacteria. In fact, some antibiotics were so strong that they don't just destroy locks but essentially tear doors apart, killing bacteria instantly.
Antibiotic 'Brute Force'
To measure the mechanical forces four types of antibiotics exerted on bacteria, researchers utilized sensitive equipment. Testing both resistant and non-resistant bacteria, the researchers observed that all of the antibiotics produced similar levels of force on non-resistant bacteria. However, forces exerted on resistant bacteria widely varied.
One of the antibiotics the researchers tested was vancomycin, a powerful drug used as a last resort for treating Methicillin-resistant Staphylococcus aureus infections and others. A modified form of vancomycin used on complex skin infections, oritavancin was also tested.
According to Ndieyira, vancomycin and oritavancin basically have the same "key" but the latter exerted force on bacteria that is 11,000 times stronger compared to the former. The researchers are not clear on how exactly oritavancin was able to effectively kill resistant bacteria, but the force the antibiotic generated was enough to tear holes into and rip apart bacteria.
Vancomycin takes between six and 24 hours to get the job done, disrupting processes to bring bacterial death. As a fast-acting antibiotic, oritavancin, on the other hand, only needs 15 minutes to work. The researchers are suggesting that oritavancin kills bacteria in a completely different manner than vancomycin as the antibiotic's molecules are good forming clusters, sticking and working together to tear bacterial surfaces apart.
Addressing Antibiotic Resistance
Ndieyira and colleagues developed a mathematical model describing antibiotic behavior on bacterial surfaces, which could be used for screening and identifying promising new antibiotics that can take advantage of brute force to kill bacteria.
Aside from guiding development of new antibiotics, the results of the study could be used in modifying existing drugs, turning them more effective at overcoming resistance. Armed with proof that modification bumps up antibiotic efficacy, the researchers are optimistic that similar things can be done, resulting in a new generation of antibiotics that can tackle multidrug-resistant bacterial infections.
The current study received funding support from the Engineering and Physical Sciences Research Council, UCL, the NIHR UCLH Biomedical Research Center, and the European Union.
