RT Journal Article
T1 Production of Ramoplanin and Ramoplanin Analogs by Actinomycetes.
A1 de la Cruz, Mercedes
A1 González, Ignacio
A1 Parish, Craig A
A1 Onishi, Russell
A1 Tormo, José R
A1 Martín, Jesús
A1 Peláez, Fernando
A1 Zink, Debbie
A1 El Aouad, Noureddine
A1 Reyes, Fernando
A1 Genilloud, Olga
A1 Vicente, Francisca
K1 actinomycetes
K1 antibacterial activity
K1 high-throughput screening
K1 microbial natural products
K1 peptidoglycan intermediate Lipid II
K1 ramoplanin
AB Ramoplanin is a glycolipodepsipeptide antibiotic obtained from fermentation of Actinoplanes sp. ATCC 33076 that exhibits activity against clinically important multi-drug-resistant, Gram-positive pathogens including vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate resistant Clostridium difficile. It disrupts bacterial cell wall through a unique mechanism of action by sequestering the peptidoglycan intermediate Lipid II and therefore does not show cross-resistance with other antibiotics. However, while demonstrating excellent antimicrobial activity in systemic use in animal models of infection, ramoplanin presents low local tolerability when injected intravenously. As a consequence of this limitation, new derivatives are desirable to overcome this issue. During a natural product screening program developed to discover compounds that disrupt bacterial cell wall synthesis by inhibiting peptidoglycan transglycosylation through binding to the intermediate Lipid II, 49 actinomycete strains were identified by HR-LCMS as producers of ramoplanin-related compounds. The producing strains were isolated from environmental samples collected worldwide comprising both tropical and temperate areas. To assess the diversity of this microbial population, the 49 isolates were initially identified to the genus level on the basis of their micromorphology, and 16S sequencing confirmed the initial identification of the strains. These analyses resulted in the identification of members of genus Streptomyces, as well as representatives of the families Micromonosporaceae, Nocardiaceae, Thermomonosporaceae, and Pseudonocardiaceae, suggesting that the production of ramoplanins is relatively widespread among Actinomycetes. In addition, all of these isolates were tested against a panel of Gram-positive and Gram-negative bacteria, filamentous fungi, and yeast in order to further characterize their antimicrobial properties. This work describes the diversity of actinomycete strains that produced ramoplanin-related compounds, and the analysis of the antimicrobial activity exhibited by these isolates. Our results strongly suggest the presence of new ramoplanin-analogs among these actinomycete producers.
SN 1664-302X
YR 2017
FD 2017-03-06
LK http://hdl.handle.net/10668/10982
UL http://hdl.handle.net/10668/10982
LA en
DS RISalud
RD Apr 6, 2025