MyxA was identified as a potent inhibitor (MICs in sub-to low µg/mL range) from a screen of purified natural products of myxobacterial origin for growth inhibitory activity against M. tuberculosis. The natural product was bactericidal against M. tuberculosis in vitro (Fig. ) and bacteriostatic ex vivo (Fig. ). Spontaneous resistant mutants of M. tuberculosis were isolated at a frequency of ~6´10 -7 at 10fold MIC. Whole-genome sequencing of mutant strains displaying MIC shifts of >40-fold (Table ) revealed mutations in rrl, the 23S ribosomal RNA gene, identifying the ribosome as the likely antibacterial target of myxovalargins. The rrl mutations associated with M. tuberculosis resistance to MyxA showed limited overlap with those found in strains resistant to the oxazolidinone antibiotic linezolid, a key component of a new treatment-shortening regimen for extensively drug-resistant tuberculosis (XDR TB) .