A new drug uses fresh tactics to kill potentially deadly drug-resistant bacteria, which have become increasingly common in recent years. The new antibiotic was described in a report published Wednesday in the journal Nature, and was reported on ScienceNews.org.
While most traditional antibiotics aim to weaken the cell wall of bacteria, or inhibit the production of key proteins, the new drug instead targets an enzyme in the cell membrane that bacteria use to secrete proteins.
The team was led by Peter Smith, an evolutionary biologist with Genentech, a biotech firm based in South San Francisco, California.
“We’re hitting a new target,” according to Smith.
The team began with natural compounds called arylomycins, according to Science, which can penetrate the outer membrane of “gram-negative” bacteria. This class of bacteria has a double cell wall that presents extra challenges for antibiotic drugs, limiting options when resistances develop. It includes diseases such as meningitis and pneumonia.
The team chemically modified the arylomycins to better bind to enzymes within the inner membrane of these cells. The new molecule, called G0775, is at least 500 times as potent as natural arylomycin in fighting disease-causing gram-negative bacteria such as Escherichia coli. But most importantly, it was just as effective against 49 different isolates of multidrug-resistant forms of these bacteria, including one particularly drug-resistant strain of K. pneumoniae.
Smith noted “We’re really excited. We’ve made the necessary changes to the molecules so that they can hit the real deal.”
Further testing will be necessary to establish that the drug won’t be toxic and will retain potency when used in larger animals, but early signs have been positive – only moderate doses were necessary to kill bacteria in mice, and it has not shown potential toxicities in mammalian cells.
Antibiotics are used frequently in both hospitals and agriculture, and drug-resistant strains of bacteria have proliferated. When only the hardiest organisms are left behind, they are able to then pass their resistance on to the next generation of bacteria.
Drug-resistance can turn familiar, normally harmless infections into potentially fatal situations for patients. The World Health Organization has warned that infectious diseases could eventually become uncontrollable as a result, and with an increasingly globalized economy, could spread rapidly around the world.
The new drug would not be a long-term solution either. If they go into widespread use, bacteria will eventually evolve resistance to them too. But for the moment, this innovation may represent a new fallback against drug-resistant bacteria.