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Biogenic Quorum-Sensing Amides from Streptomyces sp. NP10.

Marija S Genčić1, Tatjana Ilic-Tomic2, Marko Z Mladenović1,3

  • 1Department of Chemistry, Faculty of Sciences and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.

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Microbial amides from Streptomyces enhance Pseudomonas aeruginosa biofilm formation while suppressing quorum sensing (QS). These compounds, including novel natural products, offer potential for anti-virulence strategies by modulating bacterial communication.

Keywords:
1H NMR spectral simulation2-alkyl-4-quinolones (AHQs)N-acyl homoserine lactones (AHLs)Pseudomonas aeruginosa PAO1Streptomyces sp. NP10biofilm formationbiogenic amidesquorum sensingvolatile organic compounds

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Area of Science:

  • Microbiology
  • Natural Products Chemistry
  • Bacterial Communication

Background:

  • Microbial volatile organic compounds (VOCs) are key in inter- and intra-kingdom signaling.
  • Quorum sensing (QS) and biofilm formation are critical virulence factors in bacteria like Pseudomonas aeruginosa.
  • Understanding microbial signaling molecules is vital for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the ecophysiological roles of nine amides from Streptomyces sp. NP10.
  • To determine the effects of these amides on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa PAO1.
  • To identify potential anti-virulence agents from microbial metabolites.

Main Methods:

  • Gas chromatography-mass spectrometry (GC-MS) for profiling and identification of amides.
  • Chemical synthesis and spectral validation of identified compounds.
  • Co-injection experiments, biofilm assays, QS inhibition assays (AHLs and AHQs), motility assays, and cytotoxicity tests.

Main Results:

  • Identified nine amides, including two novel compounds: N-(3-methyl-2-butenyl)acetamide and N-(2-methylbutyl)acetamide.
  • Most amides enhanced P. aeruginosa biofilm formation at subinhibitory concentrations, with specific amides showing potent effects.
  • These amides suppressed QS by reducing N-acyl homoserine lactones (AHLs) and 2-alkyl-4-quinolones (AHQs), with differential effects on signaling pathways.

Conclusions:

  • The studied amides act as microbial signals modulating both QS and biofilm formation in P. aeruginosa.
  • The observed opposing effects on QS and biofilm suggest complex regulatory circuit involvement.
  • These amides, particularly non-cytotoxic ones, represent promising leads for developing anti-virulence strategies against bacterial infections.