Impact of the alkaline volatile trimethylamine on the physiology of <i>Streptomyces venezuelae</i> : an integrated transcriptomic and metabolomics study

<i>Streptomyces</i> bacteria use volatile compounds for a range of functions, including communication and to kill competing species. We previously showed that the wild-type <i>Streptomyces venezuelae</i> strain ISP5230 produces the alkaline volatile trimethylamine (TMA), which can completely rescue the morphological defects of the <i>S. venezuelae</i> mutant strain MU-1, suggesting that TMA can have a significant impact on <i>Streptomyces</i> physiology. In this study, we further characterized strain MU-1 and elucidated the effects of alkaline volatiles on <i>S. venezuelae</i> by comparing the transcriptomic data of the wild-type strain ISP5230 and strain MU-1. Our RNA-sequence analysis revealed that MU-1 exhibited differentially expressed genes (DEGs) in multiple categories, including genes involved in development, carbon metabolism, antibiotic production, and transport, and these data were verified by real-time PCR analysis. Using metabolomics analysis, we next showed that organic acids accumulated in MU-1, consistent with the acidification of the growth medium by MU-1. In addition, our quantitative analysis showed much higher residual glucose content in the growth medium of MU-1, suggesting inefficient consumption of glucose by this mutant. Notably, TMA exposure restored the normal expression pattern of the DEGs in MU-1, consistent with the ability of TMA to rescue the MU-1 phenotype, including morphology, acidification of the growth medium, glucose uptake, and antibiotic production; these findings indicated a global impact of TMA on <i>S. venezuelae</i> physiology. In conclusion, our study suggests that the alkaline volatile TMA profoundly affects the physiology of <i>S. venezuelae</i> and may promote the growth of <i>S. venezuelae</i> mutants, enabling their survival in complex microbial communities.IMPORTANCEMicrobes produce a wide array of volatile compounds for which diverse biological roles have been implicated in microbial volatiles. In <i>Streptomyces</i>, the alkaline volatile trimethylamine (TMA) enables communication between cells, and in <i>Streptomyces venezuelae</i>, TMA could also rescue the defective morphology of the mutant strain MU-1, indicating a broader impact of TMA on <i>Streptomyces</i> physiology. In this study, we identified differentially expressed genes (DEGs) in MU-1 and demonstrated that TMA exposure induced normal expression of these DEGs in the mutant strain to levels comparable with those in the wild-type strain, consistent with the ability of TMA to rescue the abnormal phenotype of this mutant. Our study expands the role of TMA to a global impact on the physiology of recipient cells and adds a new understanding of the importance of volatile compounds in microbial communities.