Peptidomimetic Antibiotics Target Outer-Membrane Biogenesis in <i>Pseudomonas aeruginosa</i>

TLDR

Pseudomonas aeruginosa is an opportunistic pathogen, and drug‑resistant strains pose a serious health problem. The peptidomimetic antibiotics target the essential outer‑membrane protein LptD involved in lipopolysaccharide assembly, without lysing the membrane. The synthesized peptidomimetic antibiotics are active against Pseudomonas, show therapeutic efficacy in a mouse infection model, and targeting LptD—widely present in gram‑negative bacteria—suggests potential for broader‑spectrum antibiotic development. Srinivas et al.

Abstract

Killing Pseudomonas Gram-negative Pseudomonas bacteria are opportunistic pathogens, and drug-resistant strains present a serious health problem. Srinivas et al. (p. 1010 ) synthesized a family of peptidomimetic antibiotics that is active only against Pseudomonas . These antibiotics do not lyse the cell membrane, but instead target an essential outer membrane protein, LptD, which plays a role in the assembly of lipopolysaccharide in the outer cell membrane. Activity in a mouse infection model suggests that the antibiotics might have therapeutic potential. In addition, LptD is widely distributed in gram-negative bacteria and so its validation as a target has the potential to drive development of antibiotics with a broader spectrum of activity against gram-negative pathogens.