Journal of Antibiotics

Two new antifungal polyketides, named cytosporones Y (1) and Z (2), were discovered from the cultured broth of Trichoderma sp. FKI-6626. Their structures were elucidated by MS and NMR analysis. Both compounds exhibited antifungal activity against five Aspergillus species, the causative agents of aspergillosis.

Two new spirotetronate class compounds designated wychimicins E (1) and F (2) were isolated from the culture extract of an actinomycete Cryptosporangium sp. RD061707. Their structures were determined through extensive NMR analysis in comparison with wychimicin C. Both compounds lack one hydroxy group in the decalin moiety, and the relative configuration of the remaining hydroxy group was assigned by NMR analysis of triacetylwychimicin E (3). Compounds 1 and 2 showed potent antimicrobial activity against Kocuria rhizophila and Staphylococcus aureus...

Sporangimicins A-D (1-4), four anomeric pairs of diacyl disaccharides that represent a new metabolite class, were discovered from the culture extract of an actinomycete Pseudosporangium sp. RD061809. Compounds 1-4 caused peak separation in the HPLC chromatogram and partial duplication of the NMR resonances by anomeric interconversion of a maltose core modified at the two sugar 6-positions with an isobutanoyl and a methyl-branched long-chain dienoyl groups. A highlight of the structure elucidation was application of Ohrui-Akasaka's method to a chromatographically inseparable mixture of 3 and 4, which proved the composition ratio of 3 and 4 to be 82:18 and the R/S ratio at the anteiso-methyl bearing chiral center in 3 to be 66:34...

This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates...

A new actinomycete strain, ODS25T , exhibited antimicrobial activity against Bacillus subtilis, Kocuria rhizophila, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, Candida tropicalis, was isolated from the ants, Odontomachus simillimus, collected from National Science Museum Thailand, Pathum Thani, Thailand. A polyphasic technique was used to characterize the taxonomic position. The morphological and chemotaxonomic properties of the strain are typical of members of the genus Streptomyces...

Most of the natural products containing tetramic acid have trans configuration of the decalin moiety. Undana A (1), a new cis decalin-bearing tetramic acid metabolite was isolated from endophytic fungi Nigrospora oryzae associated with Avicennia marina. The structure was determined based on the mass and NMR spectral data together with the comparison of the literature. This is the first report of cis decalin-tetramic acid metabolite from the mangrove endophytic fungus. Compound 1 was tested for cytotoxic against L5178Y mouse cancer cells and antibacterial activity against several gram-positive including MRSA and gram-negative bacteria but was found inactive...

Escherichia coli and Klebsiella pneumoniae are important members of the Enterobacteriaceae family, involved in many infections. The increased resistance rate towards β-lactams and fluoroquinolones -which are the main therapeutic options- limits their treatment options. This study aimed to assess the local resistance patterns against different antimicrobials and to determine the extended-spectrum β-lactamase (ESBLs) producers. The study revealed that 36% of clinical isolates were ESBL producers, showing high resistance rates towards β-lactams and non-β-lactams, especially sulphamethoxazole-trimethoprim and fluoroquinolones...

Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors. We also report in vivo efficacy in a Staphylococcus aureus murine infection model supported by corresponding pharmacokinetic studies...

Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model...

An actinomycete, designated strain CH9-7T , was isolated from the rhizosphere soil of Mangifera indica. The morphological and chemotaxonomic properties, such as the production of spiral spore chains and the presence of LL-diaminopimelic acid in the peptidoglycan, showed that it belongs to the genus Streptomyces. Based on the 16S rRNA gene analysis, it was confirmed that strain CH9-7T was a member of the genus Streptomyces and revealed 99.9% 16S rRNA gene sequence similarity to its closest relative strains, Streptomyces lydicus NBRC 13058 T and Streptomyces chattanoogensis NBRC 12754 T ...

Herbidospora is one of the underexplored actinomycete genera from which only a limited number of secondary metabolites are reported. In our continuing investigation on less explored actinomycetes, a liquid culture of Herbidospora sp. RD 11066 was found to contain unknown metabolites that had no match in our in-house UV database. Chromatographic separation and following structural analysis using NMR and MS identified these metabolites to be chromanone and chromene derivatives, which were respectively composed of an inseparable mixture of two isomeric forms...

The versatile human commensal bacteria and pathogen Staphylococcus aureus cause several community and hospital-acquired illnesses associated with significant morbidity and death. Antibiotic therapy for S. aureus infections has grown increasingly difficult as the organism has developed a wide spectrum of antibiotic resistance mechanisms. This situation emphasizes the significance of developing and advocating new antimicrobials for preventative and therapeutic measures. Our study aimed to identify and evaluate new therapeutic options against S...

This study was aimed at understanding the distributions of the MICs (minimum inhibitory concentrations) of aztreonam-avibactam, ceftazidime-avibactam and meropenem with respect to Klebsiella pneumoniae isolates producing different types of carbapenemases and their combinations. K. pneumoniae isolates were collected between 2019 and 2022 from 37 hospitals. PCR was used to screen for blaKPC -, blaNDM - and blaOXA-48 -like genes. MICs were determined by the broth microdilution method for meropenem, aztreonam-avibactam and ceftazidime-avibactam at a constant avibactam concentration of 4 mg l-1 ...

A novel actinomycete, designated as TPMA0078T , was isolated from a soil sample collected in Shinjuku, Tokyo, Japan. 16S rRNA gene sequence analysis indicated that strain TPMA0078T belongs to the genus Actinoplanes and is closely related to Actinoplanes regularis IFO 12514T (99.86% 16S rRNA gene sequence similarity). The spores of strain TPMA0078T were motile, and the sporangia were cylindrical. The diamino acids in the cell wall peptidoglycan of strain TPMA0078T were meso-diaminopimelic acid and 3OH-meso-diaminopimelic acid...

Two new depside antibiotics, geministatins A (1) and B (2), were isolated from the fungus Austroacremonium gemini MST-FP2131 (Sordariomycetes, Ascomycota), which was recovered from rotting wood in the wet tropics of northern Australia. The structures of the geministatins were elucidated by detailed spectroscopic analysis, chemical degradation and comparison with literature values. Chemical degradation of 1 and 2 yielded three new analogues, geministatins C-E (3-5), as well as a previously reported compound dehydromerulinic acid A (6)...

Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50 ) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B...

Staphylococcus aureus is one of the most common nosocomial biofilm-forming pathogens worldwide that has developed resistance mechanisms against majority of the antibiotics. Therefore, the search of novel antistaphylococcal agents with unexploited mechanisms of action, especially with antibiofilm activity, is of great interest. Seryl-tRNA synthetase is recognized as a promising drug target for the development of antibacterials. We have carried out molecular docking of compounds with antistaphycoccal activity, which were earlier found by us using phenotypic screening, into synthetic site of S...

Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli...

The development of new therapeutic uses for existing drugs is important for the treatment of some diseases. Cephalosporin antibiotics stand as the most extensively utilized antibiotics in clinical practice, effectively combating bacterial infections. Here, we found that the antimicrobial drug ceftazidime strongly upregulates p27 protein levels by inhibiting p27 ubiquitination. The p27 protein is a classic negative regulator of the cell cycle. Next, we demonstrated that ceftazidime can impede the cell cycle from G1 to S phase, thus inhibiting cell proliferation...