<i>In vitro</i> activity of MRS-2541, a novel MetRS inhibitor, against a selection of resistant gram-positive organisms associated with serious hospital infections

Infections caused by antibiotic-resistant bacteria are inherently challenging to treat. Poor outcomes, including higher death rates, are associated with infections caused by antibiotic-resistant organisms. As a result, there is an urgent need for new antibiotics, particularly ones that act via novel mechanisms that evade established resistance mechanisms. In this paper, we provide new data about MRS-2541, a preclinical antibiotic that acts by inhibiting the bacterial methionyl-tRNA synthetase. We show that MRS-2541 has potent in vitro activity against diverse strains of <i>Staphylococcus</i>, <i>Streptococcus</i>, and <i>Enterococcus</i>. For example, all 115 strains of <i>Staphylococcus</i> spp. (including 27 methicillin-resistant <i>Staphylococcus aureus</i> strains and 12 vancomycin-intermediate <i>S. aureus</i> strains) were fully susceptible to MRS-2541 with MICs of <0.25 μg/mL. The specific activity against gram-positive bacteria and sparing of gram-negative flora indicates that MRS-2541 may be less disruptive of intestinal microbiota than broad-spectrum antibiotics. MRS-2541 is a promising preclinical candidate for infections due to resistant gram-positive organisms.