Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skele-tons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitro antibacterial activity against an extensive clinical isolate collec-tion, time-kill kinetics, pharmacokinetics (PK), and in vivo efficacy of coralmycins were studied. Coralmycin A showed potent antibacterial activity with an MIC90 of 1 mg/L against 73 clinical methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci isolates, which was 2–8 times higher than the corresponding activities of DH-coralmycin A, vancomycin, daptomycin, and linezolid, and against 73 vancomycin-resistant Enterococcus and Streptococcus pneumoniae isolates, which was 4–16 times higher than the corresponding activities of DH-coralmycin A, daptomycin, and linezolid. Pharmacokinetic analysis after i.v. injection showed that coralmycins have a moderate vol-ume of distribution and moderate-to-high clearance in mice. The coralmycin A and DH-coralmycin A bioavailability values were 61.3% and 11.7%, respectively, after s.c. administration. In a mouse respiratory tract infection model, coralmycin A showed bacteriostatic and bactericidal in vivo efficacies at an s.c. administration of 4 and 100 mg/kg bid, respectively; these efficacies were similar to those of vancomycin at 4 and 20 mg/kg bid, respectively. The present findings indicate that coralmycin A has great potential as a new class of antibiotic for treating infections caused by multidrug-resistant Gram-positive bacteria.
Bibliographical noteFunding Information:
Funding: This work was funded by the Ministry of Health & Welfare, Korea through the Korea Health Technology R&D Project of the Korea Health Industry Development Institute (KHIDI) (grant number HI17C1807), the Ministry of Education, Korea, through the Basic Science Research Program of the National Research Foundation of Korea (NRF) (grant number NRF-2021R1I1A2048905) and the Korea Research Institute of Bioscience & Biotechnology (KRIBB) Research Initiative Program, Korea.
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Pharmacology, Toxicology and Pharmaceutics(all)
- Microbiology (medical)
- Infectious Diseases
- Pharmacology (medical)