BackgroundAntimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options.PurposeThus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections.MethodsWe isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method.ResultsPreliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 μg/ml and 1 μg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 μg/ml and MIC90: 4 μg/mL) and fungi (MIC50: 4 μg/ml and MIC90: 8 μg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. ConclusionS. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.

Background Newcastle disease virus (NDV) is a severe disease that affects domestic and wild birds. Controlled antibiotics derived from probiotics have been examined as prospective solutions for preserving seroconversion in NDV-vaccinated fowl. In this study, the secondary metabolite “telomycin” was extracted from Streptomyces coeruleorubidus (S. coeruleorubidus) isolated from Egypt's cultivated soil. The structure of telomycin was determined by the elucidation of spectroscopic analysis, including nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, and comparison with the literature. The antiviral activity of the secondary metabolite was tested by checking its effect on NDV hemagglutination activity (HA). Moreover, HA of NDV was tested after inoculation of NDV (control) and a combination of telomycin and NDV in 10- days- specific pathogen-free embryonated chicken eggs (SPF-ECE) daily candling. Histopathological examination was performed for chorioallantoic membranes and liver of SPF-ECE. Results S. coeruleorubidus secondary metabolite “telomycin” showed complete hemagglutination inhibition (HI) activity of NDV strain (MN635617) with log106 infectivity titers (EID50/mL). The HA of NDV strain was 8 log2 and 9 log2 with 0.5% and 0.75% of chicken RBCs, respectively. Preserved structures of chorioallantoic-membranes (CAM) with dilated capillary networks were observed in the treated group inoculated with telomycin and NDV. Histological changes in SPF-ECE liver were examined after inoculation in ova to further characterize the telomycin effect. Telomycin and NDV mixture inoculated group showed preserved cytoarchitecture of hepatocytes with the presence of perivascular foci of lymphocytes. The group that was inoculated with telomycin alone showed normal histology of hepatic acini, central veins, and portal triads. Conclusion S. coeruleorubidus telomycin is a promising bioactive agent that might be a biological weapon against a deadly chicken NDV that costs farmers a lot of money.

Background The Newcastle Disease Virus (NDV) is present throughout the world, and outbreaks in Egypt caused serious economic losses in the poultry industry. Actinobacteria are a phylum of bacteria known for their potential in producing structurally diversified natural products which promising natural compounds used to combat viruses are presented and evaluated. Streptomyces Misakimycin isolated from Egyptian soil, and evaluated for their efficacy in controlling NDV. On the basis of the biochemical characteristics S. Misakimycin metabolites, identified by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. Results In this investigation, NDV was found to have been isolated in February from a chicken farm in the Dakahlia Governorate of Egypt by the Animal Health Research Institute in Dokki, Giza. Diethylpthalate (DEP), a secondary metabolite of S. misakimycin, completely inhibited the hemagglutination (HI) activity of the NDV strain (MN635617) at log107 infectivity titers (EID50/mL). With 0.5 percent and 0.75 percent of chicken RBCs, the HA of the NDV strain was 2 log2 and 5 log2, respectively. In the treated group that received DEP and NDV inoculations, chorioallantoic-membranes (CAM) structures were preserved along with dilated capillary networks. Histological changes in SPF-ECE liver were examined after inoculation in ova to further characterize the DEP effect. Diethylpthalate and NDV mixture inoculated group showed preserved cytoarchitecture of hepatocytes with the presence of perivascular foci of lymphocytes. The group that was inoculated with telomycin alone showed normal histology of hepatic acini, central veins, and portal triads. Conclusion A potentially bioactive substance called diethylpthalate has the potential to be a biological weapon against a fatal chicken NDV that quickly increase cost losses for farmers.