Appropriate DevR (DosR)-Mediated Signaling Determines Transcriptional Response, Hypoxic Viability and Virulence of Mycobacterium tuberculosis

Background: The DevR(DosR) regulon is implicated in hypoxic adaptation and virulence of Mycobacterium tuberculosis. The present study was designed to decipher the impact of perturbation in DevR-mediated signaling on these properties. Methodology/Principal Findings: M. tb complemented (Comp) strains expressing different levels of DevR were constructed in Mut1 * background (expressing DevR N-terminal domain in fusion with AphI (DevRN-Kan) and in Mut2DdevR background (deletion mutant). They were compared for their hypoxia adaptation and virulence properties. Diverse phenotypes were noted; basal level expression (,5.362.3 mM) when induced to levels equivalent to WT levels (,25.869.3 mM) was associated with robust DevR regulon induction and hypoxic adaptation (Comp 9 * and 10*), whereas low-level expression (detectable at transcript level) as in Comp 11 * and Comp15 was associated with an adaptation defect. Intermediate-level expression (,3.361.2 mM) partially restored hypoxic adaptation functions in Comp2, but not in Comp1 * bacteria that coexpressed DevRN-Kan. Comp * strains in Mut1 * background also exhibited diverse virulence phenotypes; high/very low-level DevR expression was associated with virulence whereas intermediate-level expression was associated with low virulence. Transcription profiling and gene expression analysis revealed up-regulation of the phosphate starvation response (PSR) in Mut1 * and Comp11 * bacteria, but not in WT/Mut2DdevR/other Comp strains, indicating a plasticity in expression pathways that is determined by the magnitude of signaling perturbation through DevRN-Kan

Functional Genetic Diversity among Mycobacterium tuberculosis Complex Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival

Tuberculosis exerts a tremendous burden on global health, with ∼9 million new infections and ∼2 million deaths annually. The Mycobacterium tuberculosis complex (MTC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are more genetically and functionally diverse than appreciated previously. The impact of this natural variation on the virulence and clinical manifestations of the pathogen remains largely unknown. This report examines the effect of genetic diversity among MTC clinical isolates on global gene expression and survival within macrophages. We discovered lineage-specific transcription patterns in vitro and distinct intracellular growth profiles associated with specific responses to host-derived environmental cues. Strain comparisons also facilitated delineation of a core intracellular transcriptome, including genes with highly conserved regulation across the global panel of clinical isolates. This study affords new insights into the genetic information that M. tuberculosis has conserved under selective pressure during its long-term interactions with its human host

The evolutionary psychology of leadership trait perception

Knowles, Kristen K. - ORCID 0000-0001-9664-9055 https://orcid.org/0000-0001-9664-9055Many researchers now approach the understanding of how facial characteristics shape the perception of leadership ability through the lens of human evolution. This approach considers what skills and characteristics would have been valuable for leaders to possess in our evolutionary history, including dominance, masculinity, and trustworthiness. Moreover, it gives an understanding about why rapid categorisation of these social cues from faces is adaptive. In this chapter, I present evolutionary arguments for social inferences based on faces, and discuss how our understanding of this categorisation has shifted away from purely associative phenomena towards evolved, innate processes. I explain how the perception of leadership ability in faces is linked to variance in facial morphology, and how these morphologies tell us something about the individuals who carry them. Specific facial cues relating to leadership-relevant traits are discussed, as well as the underlying biological systems that accompany these traits. I also explain the importance of context and individual differences on the prioritisation of seemingly disparate facial cues to leadership: dominance and trustworthiness. I also discuss recent findings in this area which further extend these concepts to examine cues to leadership in women’s faces, generally overlooked by evolutionary psychologists, and how political ideology can interact with these effects.https://doi.org/10.1007/978-3-319-94535-4_5pubpu