Antibacterial polyene-polyol macrolides and cyclic peptides from the marine-derived Streptomyces sp. MS110128.

Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene macrolides, pyranpolyenolides A (1) and B (2), and one new natural cyclic peptide (9), together with two known polyenes (7 and 8) and three known cyclic peptides (10-12), were isolated from a culture of the marine Streptomyces sp. MS110128. In addition, four new polyene macrolides, pyranpolyenolides C-F (3-6), were identified as olefin geometric isomers that were most likely produced by photochemical conversion during the cultivation or isolation procedures. The pyranpolyenolides are 32-membered macrolides endowed with a conjugated tetraene and several pairs of 1,3-dihydroxyl groups. Pyranpolyenolides that contain a hydropyran group have not been previously reported. Four cyclic peptides (9-12) showed significant activities against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant S. aureus with supporting MIC values ranging from 0.025 to 1.25 µg/mL. These cyclic peptides containing piperazic moieties showed moderate activities with MIC values of 12.5 µg/mL against Bacille Calmette Guerin (BCG), an attenuated form of the bovine. Additionally, cyclic peptide 12 showed moderate antifungal activity against Candida albicans with an MIC value of 12.5 µg/mL. KEY POINTS: • Discovery of new polyenes and cyclic peptides from a marine-derived Actinomycete. • Cyclic peptides containing piperazic moieties exhibited good antibacterial activity.

Cytotoxic cardenolides from the latex of Calotropis procera.

Three new cardenolides (3, 9 and 10), along with eight known ones, were isolated from the latex of Calotropis procera. The structural determination was accomplished by the 1D- and 2D-NMR spectra as well as HRESIMS analysis. The growth inhibitory activity of the latex and its sub-fractions as well as isolated compounds was evaluated against human A549 and Hela cell lines. The results exhibited that latex had strong growth inhibitory activity with IC50s of (3.37 µM, A-549) and (6.45 µM, Hela). Among the four extracts (hexane, chloroform, ethyl acetate and aqueous), chloroform extract displayed the highest potential cytotoxic activity, with IC50s of (0.985 µM, A-549) and (1.471 µM, Hela). All the isolated compounds displayed various degrees of cytotoxic activity and the highest activity was observed by calactin (1) with IC50s values of (0.036 µM, A-549) and (0.083 µM, Hela). None of these isolated compounds exhibited good antimicrobial activity evaluated by determination of their MICs using the broth microdilution method against various infectious pathogens. The structure-activity relationships for cytotoxic activity were also discussed.

Candida albicans promotes tooth decay by inducing oral microbial dysbiosis.

Candida albicans has been detected in root carious lesions. The current study aimed to explore the action of this fungal species on the microbial ecology and the pathogenesis of root caries. Here, by analyzing C. albicans in supragingival dental plaque collected from root carious lesions and sound root surfaces of root-caries subjects as well as caries-free individuals, we observed significantly increased colonization of C. albicans in root carious lesions. Further in vitro and animal studies showed that C. albicans colonization increased the cariogenicity of oral biofilm by altering its microbial ecology, leading to a polymicrobial biofilm with enhanced acidogenicity, and consequently exacerbated tooth demineralization and carious lesion severity. More importantly, we demonstrated that the cariogenicity-promoting activity of C. albicans was dependent on PHR2. Deletion of PHR2 restored microbial equilibrium and led to a less cariogenic biofilm as demonstrated by in vitro artificial caries model or in vivo root-caries rat model. Our data indicate the critical role of C. albicans infection in the occurrence of root caries. PHR2 is the major factor that determines the ecological impact and caries-promoting activity of C. albicans in a mixed microbial consortium.