RESUMO
Mycobacterium avium complex (MAC) is a serious disease that is mainly caused by infection with the non-tuberculous mycobacteria (NTM), Mycobacterium avium and Mycobacterium intracellulare. Seven new compounds, designated mavintramycins A-G (1-7), were isolated along with structurally related compounds, including amicetin (9) and plicacetin (10), from the culture broth of Streptomyces sp. OPMA40551 as anti-MAC compounds that were active against M. avium and M. intracellulare. Among them, mavintramycin A showed the most potent and selective inhibition of M. avium and M. intracellulare. Furthermore, mavintramycin A was active against more than 40 clinically isolated M. avium, including multidrug-resistant strains, and inhibited the growth of M. avium in a persistent infection cell model using THP-1 macrophages. Mavintramycin A also exhibited in vivo efficacy in silkworm and mouse infection assays with NTM. An experiment to elucidate its mechanism of action revealed that mavintramycin A inhibits protein synthesis by binding to 23S ribosomal RNA in NTM. Mavintramycin A, with a different chemical structure from those of clinically used agents, is a promising drug candidate for the treatment of MAC infectious disease.
Assuntos
Doenças Transmissíveis , Infecção por Mycobacterium avium-intracellulare , Animais , Camundongos , Complexo Mycobacterium avium , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Mycobacterium aviumRESUMO
Two new cyclic dipeptides, paranazzamides A (1) and B (2) containing a C7-prenylated tryptophan, were isolated from a culture broth of snake fungal disease-isolate Paranannizziopsis sp. UH-21. This is the first report on the new secondary metabolites from Paranannizziopsis sp. The planar structures of 1 and 2 were elucidated using various spectroscopic techniques including MS and 1D/2D NMR. The absolute configuration of 1 was assigned by comparison with the synthesized compound. Compounds 1 and 2 exhibited no antifungal activity, no antibacterial activity, and no cytotoxic activity even at a concentration of 128 µg ml-1, whereas 1 and 2 exhibited amphotericin B potentiating activity against Candida auris in combination treatment.
Assuntos
Dipeptídeos , Peptídeos Cíclicos , Triptofano , Triptofano/química , Triptofano/metabolismo , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/isolamento & purificação , Animais , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Candida/efeitos dos fármacos , Prenilação , Anfotericina B/farmacologia , Estrutura Molecular , HumanosRESUMO
During our screening for anti-mycobacterial agents against Mycobacterium avium complex (MAC), two new polycyclic tetramate macrolactams (PTMs), named hydroxycapsimycin (1) and brokamycin (2), were isolated along with the known PTM, ikarugamycin (3), from the culture broth of marine-derived Streptomyces sp. KKMA-0239. The relative structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Furthermore, the absolute configuration of 1 was confirmed by a single-crystal X-ray diffraction analysis. Compounds 2 and 3 exhibited moderate antimycobacterial activities against MAC, including clinically isolated drug-resistant M. avium.
Assuntos
Antibacterianos , Lactamas , Testes de Sensibilidade Microbiana , Streptomyces , Streptomyces/metabolismo , Streptomyces/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Complexo Mycobacterium avium/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Lactamas Macrocíclicas/farmacologia , Lactamas Macrocíclicas/química , Lactamas Macrocíclicas/isolamento & purificação , Cristalografia por Raios X , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/isolamento & purificação , Compostos Policíclicos/farmacologia , Compostos Policíclicos/isolamento & purificação , Compostos Policíclicos/química , Estrutura MolecularRESUMO
The marine actinomycete strain OPMA02852, identified as the genus Streptomyces, was found to produce anti-mycobacterial compounds against Mycobacterium avium complex (MAC). One new compound, designated as steffimycin E (1), was isolated together with three known steffimycins (steffimycin (2), 10-dihydrosteffimycin (3), and 8-demethoxysteffimycin (4)) from the culture broth of this producing microorganism by solvent extraction, ODS column chromatography, and preparative HPLC. Compound 1 has a tetracyclic quinone structure with a sugar moiety. Compound 1 exhibited anti-mycobacterial activity against M. intracellulare, M. bovis BCG, and M. smegmatis.
Assuntos
Antraciclinas/farmacologia , Antituberculosos/farmacologia , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium avium/efeitos dos fármacos , Streptomyces/química , Antraciclinas/química , Antituberculosos/química , Linhagem Celular Tumoral , Células HeLa , Humanos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológicoRESUMO
Although the presence of Brucella spp. in the western Pacific has been suggested by epidemiological studies on cetaceans, it has not been confirmed by bacterial isolation. Here, for the first time, we report that a marine Brucella strain was isolated in the western Pacific from a bottlenose dolphin with osteomyelitis. The isolate from the lesion was confirmed to be B. ceti of sequence type 27 by multilocus sequence typing and Bruce-ladder PCR. Infrequent-restriction-site PCR and omp2 gene sequencing revealed that molecular characteristics of this isolate were similar to those of Brucella DNA previously detected from minke whales in the western North Pacific. These results suggest that genetically related Brucella strains circulate in cetacean species in this region.
Assuntos
Golfinho Nariz-de-Garrafa/microbiologia , Brucella/isolamento & purificação , Osteomielite/veterinária , Animais , Brucella/genética , Brucelose/diagnóstico , Brucelose/microbiologia , Brucelose/veterinária , DNA Bacteriano , Masculino , Tipagem de Sequências Multilocus , Osteomielite/microbiologia , Oceano Pacífico/epidemiologia , Reação em Cadeia da PolimeraseRESUMO
In 2018, Brucella ceti was isolated from a bottlenose dolphin from the western Pacific Ocean. Here, we report a draft genome sequence of the isolate BD1442 of sequence type 27, which is the only sequence type known to have been isolated from human clinical cases.