title: Pharmacological properties of the marine natural product marinopyrrole A against methicillin-resistant Staphylococcus aureus.
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.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California 92093-0687, USA.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Haste
authors.forename: Chambers C
authors.initials: CC
authors.lastname: Hughes
authors.forename: Dan N
authors.initials: DN
authors.lastname: Tran
authors.forename: William
authors.initials: W
authors.lastname: Fenical
authors.forename: Paul R
authors.initials: PR
authors.lastname: Jensen
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hensler
mesh_terms: D006367:HeLa Cells; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D044967:Serum / Q000737:chemistry
chemical_list: D011758:Pyrroles; C528298:marinopyrrole A