Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23

Abstract

Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria Corallococcus coralloides M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the β-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.

Antimicrobial textile: recent developments and functional perspective

“…Cotton-coated fabric with these structures exhibited activity against Bacillus subtilis [11]. Functional ecofriendly nanohybrid material synthesized using oligochitosan (obtained from crab shells) and nano-silica (obtained from rice husk) was resistant against Phytophthora infestans fungal attack, which points toward advanced research in the green agricultural application [12].…”

Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins

“…However, although coralmycins and cystobactamids have potent anti-Gram-positive activity against standard strains, their extensive antibacterial activity against clinical isolates and in vivo efficacy against Gram-positive strains have not yet been reported. As cystobactamids, coralmycins exert antibacterial functions by inhibiting bacterial DNA gyrase [11,12,16]. Importantly, coralmycins show significantly little cross-resistance with fluoroquinolones [10,11], suggesting a different binding site of coralmycins from that of quinolone antibiotics in DNA gyrase.…”

“…Importantly, coralmycins show significantly little cross-resistance with fluoroquinolones [10,11], suggesting a different binding site of coralmycins from that of quinolone antibiotics in DNA gyrase. Considering their novel structural scaffold and As cystobactamids, coralmycins exert antibacterial functions by inhibiting bacterial DNA gyrase [11,12,16]. Importantly, coralmycins show significantly little cross-resistance with fluoroquinolones [10,11], suggesting a different binding site of coralmycins from that of quinolone antibiotics in DNA gyrase.…”

“…Cbv34 by Muller’s group [ 11 ], has also been isolated from the coralmycin A-producing strain [ 10 ]. From a large-scale culture of Corallococcus coralloides M23, seven more new coralmycin derivatives, coralmycins C–I, have been reported [ 12 ]. Coralmycin A and DH-coralmycin A have potent antibacterial activity against important Gram-positive bacteria, including MRSA, but weak or moderate antibacterial activity against Gram-negative bacteria, such as E. coli and P. aeruginosa .…”

“…As cystobactamids, coralmycins exert antibacterial functions by inhibiting bacterial DNA gyrase [ 11 , 12 , 16 ]. Importantly, coralmycins show significantly little cross-resistance with fluoroquinolones [ 10 , 11 ], suggesting a different binding site of coralmycins from that of quinolone antibiotics in DNA gyrase.…”