Pharmacological Properties of the Marine Natural Product Marinopyrrole A against Methicillin-Resistant Staphylococcus aureus
Abstract
Pharmacological Properties of the Marine Natural Product Marinopyrrole A against Methicillin-Resistant Staphylococcus aureus ▿ Nina M. Haste 1 , 3 , Chambers C. Hughes 3 , Dan N. Tran 2 , William Fenical 1 , 3 , Paul R. Jensen 3 , Victor Nizet 1 , 2 and Mary E. Hensler 2 , * 1 Skaggs School of Pharmacy and Pharmaceutical Sciences 2 Department of Pediatrics 3 Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California—San Diego, La Jolla, California 92093-0687 ABSTRACT The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains in hospital and community settings presents a great challenge to public health and illustrates the urgency of discovering new antibiotics. Marinopyrrole A is a member of a structurally novel class of compounds identified from a species of marine-derived streptomycetes with evidence of antistaphylococcal activity. We show that marinopyrrole A has potent concentration-dependent bactericidal activity against clinically relevant hospital- and community-acquired MRSA strains, a prolonged postantibiotic effect superior to that of the current first-line agents vancomycin and linezolid, and a favorable resistance profile. Marinopyrrole A showed limited toxicity to mammalian cell lines (at >20× MIC). However, its antibiotic activity against MRSA was effectively neutralized by 20% human serum. A variety of marinopyrrole analogs were isolated from culture or synthetically produced to try to overcome the inhibitory effect of serum. While many of these compounds retained potent bactericidal effect against MRSA, their activities were also inhibited by serum. Marinopyrrole A has significant affinity for plastic and may therefore have potential as a potent anti-MRSA agent in cutaneous, intracatheter, or antibiotic-lock applications.