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.Front. Cell. Infect. Microbiol
.Front. Cell. Infect. Microbiol
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Abstract: |
Background: 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.
Purpose: 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.
Methods: We 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.
Results: Preliminary 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 mg/ml and 1 mg/mL, respectively, versus S.
coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl2-butenyl ester against bacteria (MIC50: 2 mg/ml and MIC90: 4 mg/mL) and fungi
(MIC50: 4 mg/ml and MIC90: 8 mg/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 vancomycinresistant 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.
Conclusion: S. 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.
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