AUTHOR=Abdelaziz Rewan , Tartor Yasmine H. , Barakat Ahmed B. , EL-Didamony Gamal , Gado Marwa M. , Berbecea Adina , Radulov Habil dr. Isidora 

TITLE=Bioactive metabolites of Streptomyces misakiensis display broad-spectrum antimicrobial activity against multidrug-resistant bacteria and fungi

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1162721

DOI=10.3389/fcimb.2023.1162721

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Antimicrobial 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.</p></sec><sec><title>Purpose</title><p>Thus, 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.</p></sec><sec><title>Methods</title><p>We isolated <italic>Streptomyces</italic> 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.</p></sec><sec><title>Results</title><p>Preliminary screening revealed that <italic>Streptomyces misakiensis</italic> and <italic>S. coeruleorubidus</italic> exhibited antimicrobial potential. The MIC<sub>50</sub> and MIC<sub>90</sub> 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 <italic>S. coeruleorubidus</italic> metabolites: thiocarbamic acid, <italic>N,N</italic>-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC<sub>50</sub>: 2 μg/ml and MIC<sub>90</sub>: 4 μg/mL) and fungi (MIC<sub>50</sub>: 4 μg/ml and MIC<sub>90</sub>: 8 μg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of <italic>Streptococcus pyogenes</italic>, <italic>S. agalactiae</italic>, <italic>Escherichia coli, Klebsiella pneumoniae</italic>, and <italic>Salmonella</italic> enterica serovars, colistin-resistant <italic>Aeromonas hydrophila</italic> and <italic>K. pneumoniae</italic>, and vancomycin-resistant <italic>Staphylococcus aureus</italic>. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant <italic>Candida albicans</italic>, <italic>Cryptococcus neoformans</italic>, <italic>C. gattii, Aspergillus flavus, A. niger</italic>, and <italic>A. fumigatus</italic>. Ursolic acid methyl ester was applied <italic>in vivo</italic> for treating <italic>S. aureus</italic> septicemia and <italic>K. pneumoniae</italic> 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 (<italic>P</italic> &lt; 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. </p></sec><sec><title>Conclusion</title><p><italic>S. misakiensis</italic> 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.</p></sec>