Transcriptome Changes of Mycobacterium marinum in the Process of Resuscitation From Hypoxia-Induced Dormancy

Abstract

Nearly one-third of the world's population is latently infected with <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>), which represents a huge disease reservoir for reactivation and a major obstacle for effective control of tuberculosis. During latent infection, <i>M. tb</i> is thought to enter nonreplicative dormant states by virtue of its response to hypoxia and nutrient-deprived conditions. Knowledge of the genetic programs used to facilitate entry into and <i>exit</i> from the nonreplicative dormant states remains incomplete. In this study, we examined the transcriptional changes of <i>Mycobacterium marinum</i> (<i>M. marinum</i>), a pathogenic mycobacterial species closely related to <i>M. tb</i>, at different stages of resuscitation from hypoxia-induced dormancy. RNA-seq analyses were performed on <i>M. marinum</i> cultures recovered at multiple time points after resuscitation. Differentially expressed genes (DEGs) at each time period were identified and analyzed. Co-expression networks of transcription factors and DEGs in each period were constructed. In addition, we performed a weighted gene co-expression network analysis (WGCNA) on all genes and obtained 12 distinct gene modules. Collectively, these data provided valuable insight into the transcriptome changes of <i>M. marinum</i> upon resuscitation as well as gene module function of the bacteria during active metabolism and growth.