Quorum sensing is known to play a major role in the regulation of secondary metabolite production, especially, antibiotics, and morphogenesis in the phylum Actinobacteria. Although it is one of the largest bacterial phylum, only 25 of the 342 genera have been reported to use quorum sensing. Of these, only nine have accompanying experimental evidence; the rest are only known through bioinformatic analysis of gene/genome sequences. It is evident that this important communication mechanism is not extensively explored in Actinobacteria. In this review, we summarize the different quorum sensing systems while identifying the limitations of the existing screening strategies and addressing the improvements that have taken place in this field in recent years. The γ-butyrolactone system turned out to be almost exclusively limited to this phylum. In addition, methylenomycin furans, AI-2 and other putative AHL-like signaling molecules are also reported in Actinobacteria. The lack of existing screening systems in detecting minute quantities and of a wider range of signaling molecules was a major reason behind the limited information available on quorum sensing in this phylum. However, recent improvements in screening strategies hold a promising future and are likely to increase the discovery of new signaling molecules. Further, the quorum quenching ability in many Actinobacteria has a great potential in controlling the spread of plant and animal pathogens. A systematic and coordinated effort is required to screen and exploit the enormous potential that quorum sensing in the phylum Actinobacteria has to offer for human benefit.
Concerning the biological interactions within the gut microbiome, the specialized small molecules encoded by commensal microbes mediate distinct functional aspects. However, the landscape of antagonistic interactions mediated by specialized strains and their small molecules broadly remains. Here, we sought to evaluate antimicrobial interactions as a defensive contributor to gain new insights into structure-related functions or to bring the therapeutic potential of derived molecules. We elucidated the antagonistic landscape within a collection of 330 human-gut-derived commensal microbial strains cultivated from healthy human subjects. We characterized potential antagonistic strains and found a strain-specific selective inhibition contrary to common antimicrobial drugs that wipe out a broad range of species usually found in environmental microbes. Using functional and genomic approaches for accessing biologically active natural product molecules, we identified significant biosynthetic gene clusters (BGCs) encoding the important compound families in representative gut strains which contribute to antagonistic activities and are important in host defense or maintaining homeostasis in the gut. The subsets of the BGCs were represented in metagenomics sequencing data from healthy individuals. The cell culture secretome of strains revealed potential biomarkers linked to hallmark pathways. Together, these microorganisms encode biosynthetic novelty and represent a source of biologically significant natural products important in developing new treatments for infectious diseases to cut the usage of broad-spectrum antibiotics and represent a way to combat antimicrobial resistance. Consortia of such strains can be utilized as an option for precise editing of the microbiomes or fine-tuning the microbiota-modulating therapies
The bacterial phylum Actinobacteria encompasses microorganisms with incomparable metabolic versatility and deep resource of medicines. However, the recent decrease in the discovery rate of antibiotics warrant innovative strategies to harness actinobacterial resources for lead discovery. Indeed, microbial culturing efforts measuring the outcomes of specific genera lagged behind the detected microbial potential. Herein, we used a distinct competitive strategy that exploits competitive microbial interactions to accelerate the diversification of strain libraries producing antibiotics. This directed-evolution-based strategy shifted the diversity of Actinobacteria experimental over the time course (0-8 days) and led to the isolation of Actinobacterial strains with distinct antimicrobial spectrum against pathogens. To understand the competitive interactions over experimental time course, the metagenomic community sequencing revealed that actinobacterial members from families Nocardiaceae and Cellulomonadaceae with relatively increased abundances towards end, are thus competitively advantageous. Whilst comparing the Actinobacteria retrieved in the competitive strategy to that of the routinely used isolation method, the Actinobacteria genera identified from competitive communities differed relatively in abundances as well as antimicrobial spectrum compared to actinobacterial strains retrieved in classical method. In sum, we present a strategy that influences microbial interactions to accelerate the likelihood of potential actinobacterial strains with antimicrobial potencies
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