Hetiamacin E and F, New Amicoumacin Antibiotics from Bacillus subtilis PJS Using MS/MS-Based Molecular Networking

Wang, Ting; Lu, Qinpei; Sun, Cheng‐Hang; Lukianov, Dmitrii A.; Osterman, Ilya А.; Сергиев, Петр В.; Dontsova, Olga А.; Hu, Xinxin; You, Xuefu; Liu, Shaowei; Wu, Gang

doi:10.3390/molecules25194446

Cited by 19 publications

(12 citation statements)

References 40 publications

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“…As a biosensor of antimicrobial activity, the described assay was reported to be successfully applied for identification of a series of promising antibiotics whose antibacterial activity had not been reported previously, such as 2-Guanidino-quinazolines ( Komarova et al, 2017 ), N-pyridyl-substituted carboxypiperidine amides ( Ivanenkov et al, 2019b ), and N-substituted triazolo-azetidines ( Ivanenkov et al, 2019c ). Furthermore, in our previous study, this platform contributed to effective discovery of some novel antibiotics that act via the translation inhibition mechanism, such as Beilunmycin ( Jiang et al, 2020 ), Hetiamacin E and F ( Wang et al, 2020b ), acetyl-griseoviridin, and desulphurizing griseoviridin ( Wang et al, 2020a ). In the present research, two Streptomyces strains and two Saccharothrix strains induced Katushka2S expression, demonstrating the protein inhibitory activities in their ethyl acetate extractions.…”

Section: Discussionmentioning

confidence: 99%

Bioprospecting of Soil-Derived Actinobacteria Along the Alar-Hotan Desert Highway in the Taklamakan Desert

Liu

Wang

et al. 2021

Front. Microbiol.

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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.

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Section: Discussionmentioning

confidence: 99%

Bioprospecting of Soil-Derived Actinobacteria Along the Alar-Hotan Desert Highway in the Taklamakan Desert

Liu

Wang

et al. 2021

Front. Microbiol.

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“…In contrast, thiocillin targets the gram-negative bacterium Pseudomonas aeruginosa by binding to ferrioxamine receptor FoxA, which disrupts the proton motive force to inhibit translation [ 113 ]. Hetiamacin E and F (39–40) ( Figure 10 ) produced from B. subtilis PJS display antibacterial activity against methicillin-resistant Staphylococcus aureus, with MIC values of 8–16 µg/mL and 32 µg/mL, respectively [ 114 ]. Hetiamacin E and F inhibit protein biosynthesis, resulting in the disruption of mRNA translation, leading to cell death [ 114 ].…”

Section: Antimicrobial Metabolites and Their Mechanism Of Actionmentioning

confidence: 99%

“…Hetiamacin E and F (39–40) ( Figure 10 ) produced from B. subtilis PJS display antibacterial activity against methicillin-resistant Staphylococcus aureus, with MIC values of 8–16 µg/mL and 32 µg/mL, respectively [ 114 ]. Hetiamacin E and F inhibit protein biosynthesis, resulting in the disruption of mRNA translation, leading to cell death [ 114 ]. Rhizocticin A (41) ( Figure 10 ) is a potent antifungal first produced from B. subtilis 6633.…”

Section: Antimicrobial Metabolites and Their Mechanism Of Actionmentioning

confidence: 99%

Antimicrobial Bacillus: Metabolites and Their Mode of Action

Tran

Cock

Chen³

et al. 2022

Antibiotics

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The agricultural industry utilizes antibiotic growth promoters to promote livestock growth and health. However, the World Health Organization has raised concerns over the ongoing spread of antibiotic resistance transmission in the populace, leading to its subsequent ban in several countries, especially in the European Union. These restrictions have translated into an increase in pathogenic outbreaks in the agricultural industry, highlighting the need for an economically viable, non-toxic, and renewable alternative to antibiotics in livestock. Probiotics inhibit pathogen growth, promote a beneficial microbiota, regulate the immune response of its host, enhance feed conversion to nutrients, and form biofilms that block further infection. Commonly used lactic acid bacteria probiotics are vulnerable to the harsh conditions of the upper gastrointestinal system, leading to novel research using spore-forming bacteria from the genus Bacillus. However, the exact mechanisms behind Bacillus probiotics remain unexplored. This review tackles this issue, by reporting antimicrobial compounds produced from Bacillus strains, their proposed mechanisms of action, and any gaps in the mechanism studies of these compounds. Lastly, this paper explores omics approaches to clarify the mechanisms behind Bacillus probiotics.

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“…To combat the escalating levels of antibiotic resistance, novel strategies are being developed to address the ongoing demand for new natural antibiotics. The study by Wang et al, 2021 aimed to investigate amicoumacin antibiotics from the desert-derived Bacillus subtilis PJS by using the modern MS/MS-based molecular networking approach [ 15 ]. Hetiamacin E had strong antibacterial activity on methicillin-sensitive and -resistant Staphylococcus epidermidis at 2–4 µg/mL, and methicillin-sensitive and -resistant Staphylococcus aureus at 8–16 µg/mL.…”

mentioning

confidence: 99%