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Whole-Cell MALDI-ToF MS Coupled with Untargeted Metabolomics Facilitates Investigations of Microbial Chemical

Nicole Aiosa1, Anupama Sinha2, Hanan Albataineh1

  • 1School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA 30332, USA.

Chembiochem : a European Journal of Chemical Biology
|February 3, 2023
PubMed

Insights

Probiotics can combat drug-resistant pathogens by producing natural products (NPs). Whole-cell MALDI-ToF mass spectrometry identified a novel NP from Bacillus velezensis interacting with Burkholderia thailandensis.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Drug-resistant pathogens pose a significant global health threat, necessitating novel therapeutic strategies.
  • Probiotics offer a promising approach to combat pathogens through direct antagonism or competitive exclusion.
  • Understanding microbe-microbe interactions, particularly probiotic-pathogen communication via natural products (NPs), is crucial for developing effective interventions.

Purpose of the Study:

  • To develop and apply a whole-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry method for characterizing natural product (NP) production in microbial co-cultures.
  • To investigate the interactions between candidate probiotic bacteria from the mouse airway microbiome and the respiratory pathogen Burkholderia.
  • To identify novel bioactive compounds involved in probiotic-pathogen interactions.

Main Methods:

  • Co-cultivation of candidate probiotic strains (mouse airway microbiome isolates) with Burkholderia species.
  • Whole-cell MALDI-ToF mass spectrometry for direct analysis of natural product profiles from co-cultures.
  • Dereplication of detected natural products against known compound databases to identify novel molecules.

Main Results:

  • A Bacillus velezensis strain was identified that inhibits the growth of Burkholderia thailandensis.
  • Co-cultivation with B. thailandensis elicited significant changes in the natural product (NP) profile of B. velezensis.
  • Analysis suggested the involvement of a previously unannotated bioactive compound in the observed interaction.

Conclusions:

  • Whole-cell MALDI-ToF mass spectrometry is a broadly applicable method for screening the natural product composition of microbial co-cultures.
  • This technique can be integrated with other omics approaches to elucidate complex microbe-microbe interactions.
  • The findings highlight the potential of specific probiotics and their natural products in developing new strategies against bacterial pathogens.
Keywords:
Bacillus sp.Burkholderia thailandensismass spectrometrymass spectrometry imagingmetabolomicsmolecular networkingnatural productswhole-cell MALDI-ToF

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