Using a novel technique to culture soil bacteria that previously could not be grown in the laboratory, a team of U.S. scientists has isolated a promising new antibiotic to which resistance may not develop easily.
The research, published this week in Nature , comes at a time when there is growing alarm both at the spread of antibiotic-resistant microbes and the failure to find new classes of antibiotics in recent decades.
During the ‘golden age of antibiotics’ from about 1940 to around 1960, scientists were able to find a number of new drugs by carefully screening soil bacteria, looking for anti-microbial activity. However, they were able to examine only bacteria that could be grown in the laboratory and more than 99 per cent of the bacterial species in the soil resisted such efforts, with the result that such leads eventually petered out.
Dr. Kim Lewis, director of the Antimicrobial Discovery Center at the Northeastern University in the U.S., and colleagues used an ‘isolation chip’ (iChip) developed at the university to culture previously uncultivable soil bacteria.
This chip has a larger number of tiny chambers to hold individual bacterial cells. Covered with semi-permeable membranes, the chip could be then placed in the soil, allowing vital nutrients and growth factors to diffuse into its chambers.
With the iChip, the scientists could grow 10,000 bacterial strains. The extract from one such bacterium, provisionally named Eleftheria terrae , yielded an entirely new sort of antibiotic, teixobactin.
Laboratory tests showed that this molecule was effective against many human pathogens, including drug-resistant ones, that come in the category of gram-positive bacteria.
The drug was “exquisitely active” against a number of hard-to-deal-with bugs, said Dr. Lewis during a press briefing. It might also offer a single-drug therapy for tuberculosis, which currently required prolonged treatment with a multi-drug combination.
Teixobactin worked by binding to highly conserved precursors that bacteria used to build their cell walls, according to Tanja Schneider of the University of Bonn in Germany, one of the co-authors of the Nature paper, whose team worked on the drug’s mode of action.
Even when the susceptible forms of the bacterium Staphylococcus aureus and the one that causes tuberculosis, Mycobacterium tuberculosis , were grown in the presence of low doses of the antibiotic, drug-resistant mutants could not be found.
Nor did such mutants evolve after S. aureus cultures were repeatedly exposed to sub-lethal doses of the antibiotic over several days.
It could be that resistance was less likely to develop against antibiotics that targeted precursors for cell wall synthesis, observed Gerard Wright of McMaster University, Canada, in a commentary published in the same journal.
When, on the other hand, the antibiotic acted on bacterial proteins, genes for those proteins could mutate and produce resistance.
Resistance against vancomycin, which too binds to cell-wall precursors, did not emerge in the clinic till almost four decades after its discovery, he pointed out. Such resistance came about through genes for a self-protective mechanism used by vancomycin-producing bacteria getting transferred to pathogenic strains.
The bacterium producing teixobactin, on the other hand, was protected by an outer membrane, and so there was no self-resistance mechanism that could be passed on, he noted.
The drug could be ready to go into clinical trials two years from now, according to Dr. Lewis.
