Drug-resistant bacteria infect two million people per year, and are capable of developing resistance to antibiotics faster than the scientific community can create new drugs (1). Professors Kim Lewis and Slava Epstein at Northeastern University, and colleagues from University of Bonn, NovoBiotic Pharmaceuticals, and Selcia Limited have made breakthroughs that suggest ways to combat this global problem. Using a novel incubation method, they have discovered a new antibiotic teixobactin that has proven effective against drug resistant strains of gram-positive bacteria (1).
Staphylococcus aureus surrounding a white blood cell (4).
Most researchers develop antibiotics by screening bacteria grown in a petri dish. However, this approach only examines one percent of microorganisms from soil, as most soil-borne bacteria will not grow under standard laboratory conditions (2). In this study, Epstein and Lewis used an iChip, which they invented in 2010. The iChip allows researchers to grow about half of the soil microorganisms that do not normally survive in the laboratory (2).
The researchers first segregated each bacterial cell from a sample of soil to a separate chamber in the iChip. Then they placed the iChip back in the soil with semipermeable membranes, permitting certain nutrients and growth factors to diffuse into the chambers and thus the bacteria to grow in their natural environment. The bacteria produced colonies that were then extracted and grown on petri dishes.
Bacteria are classified as gram-negative or gram-positive bacteria based on their cell wall’s compatibility with the Gram stain. The antibiotic teixobactin was isolated from Eleftheria terrae, a type of Gram-negative bacteria (2). During testing, teixobactin was ineffective against most Gram-negative bacteria, but very effective against Gram-positive pathogens, including drug-resistant strains of Staphylococcus aureus and Mycobacterium tuberculosis (2). It was also active against Clostridium difficile and Bacillus anthracis, which cause colitis and anthrax respectively (2).
Teixobactin operates by binding to a particular section of lipid II that is highly conserved amongst bacteria and to lipid III (2). By binding to lipid II (the precursor to peptidoglycan, a vital component of bacterial cell walls), teixobactin inhibits cell wall synthesis. Teixobactin further destabilizes bacterial cell walls by binding to lipid III, a precursor of teichoic acid that aids in the stabilization of peptidoglycan. By inhibiting cell wall synthesis, teixobactin effectively kills Gram-positive bacteria.
Teixobactin has strong potential to be used as a new antibiotic, because it does not become incorporated into DNA, RNA, or protein (2). When injected in mice, teixobactin remained effective against S. aureus and Streptococcus pneumoniae without causing detectable side effects (2).
The researchers acknowledge that resistance to teixobactin may emerge, but noted that it took 30 years for resistance to the antibiotic vancomycin (commonly used against S. aureus and other Gram-positive bacteria) to develop. They speculate that because teixobactin is even rarer than vancomycin, a comparative level of resistance will take even longer to emerge.
Teixobactin will not be tested on humans for another two years and will require several more years to be eligible to pass FDA regulations (3). If found to be effective and safe in humans, teixobactin will likely have a positive impact on the defense against harmful Gram-positive bacteria. The research foreshadows a new era of antibiotics discovery and the potential to combat multidrug resistant bacteria.
Sources:
1. Centers for Disease Control and Prevention. (2014, August 6). Antibiotic / Antimicrobial Resistance. Retrieved January 11, 2015, from http://www.cdc.gov/drugresistance/
2. Ling, L. L., Schneider, T., Peoples, A. J., Spoering, A. L., Engels, I., Conlon, B. P., . . . Lewis, K. (2015). A new antibiotic kills pathogens without detectable resistance. Nature, 1-18. http://dx.doi.org/10.1038/nature14098
3. Grady, D. (2014, January 8). New antibiotic stirs hope against resistant bacteria. New York Times, sec. A, p. 13.
4. National Institutes of Health. (2009, January 26). Staph aureus outside a white blood cell [Photograph]. Retrieved from http://commons.wikimedia.org/wiki/File:Staph_aureus_outside_a_white_blood_cell.jpg
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