Abstract
Taklamakan desert is known as the largest dunefield in China and as the second largest shifting sand desert in the world. Although with long history and glorious culture, the Taklamakan desert remains largely unexplored and numerous microorganisms have not been harvested in culture or taxonomically identified yet. The main objective of this study is to explore the diversity, novelty, and pharmacological potential of the cultivable actinomycetes from soil samples at various sites along the Alar-Hotan desert highway in the Taklamakan desert. A total of 590 actinobacterial strains were recovered by the culture-dependent approach. Phylogenetic analysis based on 16S ribosomal RNA (rRNA) gene sequences unveiled a significant level of actinobacterial diversity with 55 genera distributed in 27 families of 12 orders. Thirty-six strains showed relatively low 16S rRNA similarities (<98.65%) with validly described species, among which four strains had already been characterized as novel taxa by our previous research. One hundred and forty-six actinobacterial isolates were selected as representatives to evaluate the antibacterial activities and mechanism of action by the paper-disk diffusion method and a double fluorescent protein reporter “pDualrep2” system, respectively. A total of 61 isolates exhibited antagonistic activity against the tested “ESKAPE” pathogens, among which seven strains could produce bioactive metabolites either to be able to block translation machinery or to induce SOS-response in the pDualrep2 system. Notably, Saccharothrix sp. 16Sb2-4, harboring a promising antibacterial potential with the mechanism of interfering with protein translation, was analyzed in detail to gain deeper insights into its bioactive metabolites. Through ultra-performance liquid chromatography (UPLC)-quadrupole time-of-flight (QToF)-MS/MS based molecular networking analysis and databases identification, four families of compounds (1–16) were putatively identified. Subsequent bioassay-guided separation resulted in purification of four 16-membered macrolide antibiotics, aldgamycin H (8), aldgamycin K (9), aldgamycin G (10), and swalpamycin B (11), and their structures were elucidated by HR-electrospray ionization source (ESI)-MS and NMR spectroscopy. All compounds 8–11 displayed antibacterial activities by inhibiting protein synthesis in the pDualrep2 system. In conclusion, this work demonstrates that Taklamakan desert is a potentially unique reservoir of versatile actinobacteria, which can be a promising source for discovery of novel species and diverse bioactive compounds.
Highlights
The finding of novel bioactive compounds is a never-ending process, to meet the everlasting demand for novel drug with antimicrobial properties in order to combat escalating levels of antibiotic resistance in pathogenic microorganisms (Chokshi et al, 2019; Ardal et al, 2020)
The results showed 590 out of 860 isolates were confirmed as actinobacterial strains and assigned to 55 genera in 27 families of 12 orders (Supplementary Table S3), which was further supported by analysis of their 16S ribosomal RNA (rRNA) gene sequence-based dendrogram (Figure 2)
The study reported a relatively integrated investigation on the diversity, novelty, and pharmacological potential of actinobacterial strains isolated from eight soil samples at various sites along the Alar-Hotan desert highway in the Taklamakan desert
Summary
The finding of novel bioactive compounds is a never-ending process, to meet the everlasting demand for novel drug with antimicrobial properties in order to combat escalating levels of antibiotic resistance in pathogenic microorganisms (Chokshi et al, 2019; Ardal et al, 2020). Until April 2020, there are 41 new antibiotics under global clinical development, but only 13 of them have the potential to treat pathogens on the WHO’s critical threat list (Pew Charitable Trusts, 2020) This fact has resulted in today’s eminent lack of new antibiotic drug leads, making us face a looming crisis that the emergence of resistance is outpacing the development of new antibiotics (Dickey et al, 2017; Woodworth et al, 2018). The previous admonitory terms of “gloom scenario,” “dark horizons,” and “back to the pre-antibiotic era” are becoming reality nowadays (Bravo et al, 2018) All these facts impel scientists to rapidly explore new chemical entities for developing novel antibiotics to target the emerging multidrug-resistant microbial pathogens that cause life-threatening infections
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