As you may have seen in the news earlier this year, there is a new potential antibiotic in testing with activity against gram-positives (and even AFB such as M TB) and, as some have noted, no potential for antibiotic resistance (yet). This antibiotic, Teixobactin, was discovered using a novel technique, referred to as the I-Chip. Teixobactin is the first member of a novel class of peptidoglycan synthesis inhibitors (Ling et al., 2015). The compound is highly potent against a broad range of Gram-positive microbes, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Teixobactin binds to two different targets – lipid II (peptidoglycan precursor) and lipid III (teichoic acid precursor). It binds to the undecaprenyl-PP-sugar region of these precursors, which is not known to be modified. As a result, teixobactin is the first example of a target-specific compound essentially free of resistance. Teixobactin shows excellent activity in several models of infection, and is in preclinical development.
Teixobactin had excellent activity against Gram-positive pathogens, including drug-resistant strains. Potency against most species, including difficult-to-treat enterococci and M. tuberculosis was below 1 µg ml−1. Teixobactin was exceptionally active against Clostridium difficile and Bacillus anthracis (minimal inhibitory concentration (MIC) of 5 and 20 ng ml−1, respectively). Teixobactin had excellent bactericidal activity against S. aureus, was superior to vancomycin in killing late exponential phase populations, and retained bactericidal activity against intermediate resistance S. aureus (VISA). Note that frequent clinical failure in patients with S. aureus MRSA treated with vancomycin has been linked to the poor bactericidal activity of this compound. Teixobactin was ineffective against most Gram-negative bacteria, but showed good activity against a strain ofE. coli asmB1 with a defective outer membrane permeability barrier.
- Nature 517, 455–459, (22 January 2015). doi:10.1038/nature14098