A new class of antibiotics has been discovered by researchers, targeting the lipopolysaccharide (LPS) transporter. This discovery offers a promising treatment option for patients with invasive infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). The novel class of antibiotics, known as tethered macrocyclic peptide (MCP) antibiotics, has been identified and optimized to effectively treat highly drug-resistant CRAB isolates.
The MCP antibiotics work by blocking the transport of bacterial LPS through inhibition of the LptB2FGC complex. This represents an unprecedented antibiotic target in Acinetobacter. The tethered tripeptide structure of MCPs is not expected to be susceptible to existing mechanisms of antibiotic resistance.
A clinical candidate derived from the MCP class, zosurabalpin (RG6006), has been found to effectively treat drug-resistant CRAB isolates both in vitro and in mouse models. Zosurabalpin has demonstrated potent activity against infections caused by pan-drug resistant strains of A. baumannii. The in vitro antibacterial and pharmacokinetic properties of zosurabalpin have been validated in non-clinical data, supporting its selection as a suitable clinical development drug.
The discovery of this novel antibiotic class targeting the LPS transporter offers a promising treatment option for patients with invasive infections due to CRAB, for whom current treatment options are inadequate. This chemical class also identifies LptB2FGC as a tractable target for antimicrobial drug development. The development of MCP antibiotics represents a significant step forward in overcoming existing antibiotic resistance mechanisms and addressing the global health threat posed by drug-resistant bacteria.