Aiosa Nicole, Sinha Anupama, Albataineh Hanan, Phillips Ashlee M, Mageeney Catherine M, Wilde Delaney S, Williams Kelly P, Collette Nicole M, Branda Steven S, Garg Neha
School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA 30332, USA.
Biotechnology & Bioengineering, Sandia National Laboratories, 7011 East Avenue, Livermore, CA 94550, USA.
Chembiochem. 2023 Apr 3;24(7):e202200802. doi: 10.1002/cbic.202200802. Epub 2023 Mar 10.
The emergence of drug-resistant pathogens necessitates the development of new countermeasures. In this regard, the introduction of probiotics to directly attack or competitively exclude pathogens presents a useful strategy. Application of this approach requires an understanding of how a probiotic and its target pathogen interact. A key means of probiotic-pathogen interaction involves the production of small molecules called natural products (NPs). Here, we report the use of whole-cell matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry to characterize NP production by candidate probiotics (mouse airway microbiome isolates) when co-cultured with the respiratory pathogen Burkholderia. We found that a Bacillus velezensis strain inhibits growth of and elicits NP production by Burkholderia thailandensis. Dereplication of known NPs detected in the metabolome of this B. velezensis strain suggests that a previously unannotated bioactive compound is involved. Thus, we present the use of whole-cell MALDI as a broadly applicable method for screening the NP composition of microbial co-cultures; this can be combined with other -omics methods to characterize probiotic-pathogen and other microbe-microbe interactions.
耐药病原体的出现使得开发新的应对措施成为必要。在这方面，引入益生菌以直接攻击或竞争性排除病原体是一种有用的策略。应用这种方法需要了解益生菌与其目标病原体如何相互作用。益生菌与病原体相互作用的一个关键方式涉及称为天然产物（NPs）的小分子的产生。在此，我们报告了使用全细胞基质辅助激光解吸/电离飞行时间（MALDI-ToF）质谱来表征候选益生菌（小鼠气道微生物群分离株）与呼吸道病原体伯克霍尔德菌共培养时NP的产生情况。我们发现一株贝莱斯芽孢杆菌抑制泰国伯克霍尔德菌的生长并引发其产生NP。对在该贝莱斯芽孢杆菌菌株代谢组中检测到的已知NP进行去重复分析表明，涉及一种先前未注释的生物活性化合物。因此，我们展示了使用全细胞MALDI作为一种广泛适用的方法来筛选微生物共培养物的NP组成；这可以与其他组学方法相结合，以表征益生菌与病原体以及其他微生物之间的相互作用。
