Mycobacterial Diseases
Open Access

Light and Gene Changes in the Pathogen Mycobacterium kansasii

Luis Budell^{* *}Correspondence: Luis Budell, Department of Biology, City University of New York, Brooklyn, USA, Email:

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Description

Mycobacterium kansasii, a slow-growing, Non-Tuberculous Mycobacterium (NTM), is a significant opportunistic pathogen. It primarily affects immunocompromised individuals, leading to pulmonary diseases similar to tuberculosis. An intriguing characteristic of M. kansasiii is its ability to produce carotenoids, pigments typically associated with photosynthetic organisms. This study delves into the genetic basis of carotenogenesis in M. kansasii and examines how light exposure influences its transcriptome, potentially impacting its pathogenicity. Carotenoids are synthesized through a well-conserved pathway involving key genes, including crtB, which encodes phytoene synthase, and crtI, responsible for phytoene desaturase. These genes are regulated by environmental factors, notably light, which triggers a complex transcriptional response.

Carotenogenesis in Mycobacterium kansasii

Carotenoids are isoprenoid pigments with antioxidant properties, protecting cells from oxidative stress. In mycobacteria, carotenogenesis is facilitated by a series of genes that encode enzymes responsible for the biosynthesis of these pigments. In M. kansasiii, the crtB and crtI genes play important roles in this process. The crtB gene encodes phytoene synthase, initiating carotenoid synthesis by converting geranylgeranyl pyrophosphate to phytoene. The crtI gene encodes phytoene desaturase, which subsequently converts phytoene to lycopene, a precursor to various carotenoids.

Light-induced transcriptome remodelling

Light is an important environmental factor for influencing bacterial physiology. In M. kansasiii, exposure to light triggers a cascade of gene expression changes, affecting various cellular processes, including carotenogenesis. To investigate this phenomenon, we conducted RNA sequencing (RNA-seq) analysis on M. kansasiii cultures exposed to light and compared them to those kept in the dark. Our transcriptome analysis revealed significant upregulation of genes involved in carotenogenesis upon light exposure, including crtB and crtI.

Regulatory mechanisms

The regulatory network governing light-induced transcriptome changes in M. kansasiii involves several key players. Among these, Two-Component Systems (TCS) are prominent. TCS typically consist of a sensor kinase that detects environmental signals and a response regulator that modulates gene expression. In M. kansasii, we identified a TCS homologous to the wellcharacterized DosR-DosS system in Mycobacterium tuberculosis, which is known to respond to hypoxia and other stress conditions. Our findings suggest that this TCS may also respond to light, integrating environmental signals into the regulatory network that controls carotenogenesis and other stress responses. Another critical component is the sigma factor network. Sigma factors are proteins that bind to RNA polymerase and direct it to specific promoters, initiating transcription. In M. kansasiii, several sigma factors were differentially expressed in response to light, indicating their role in fine-tuning the transcriptional response to environmental changes.

Implications for pathogenicity

Understanding the genetic and regulatory mechanisms underlying carotenogenesis and light-induced transcriptome remodelling in M. kansasiii has significant implications for its pathogenicity. Carotenoids not only protect against oxidative damage but also modulate the immune response, potentially enhancing the survival of M. kansasiii within host cells. Moreover, light-induced changes in gene expression may affect the bacterium's virulence factors, influencing its ability to cause disease. The insights gained from this study could inform the development of novel therapeutic strategies targeting the regulatory pathways involved in carotenogenesis and lightinduced responses. For instance, disrupting the function of key regulatory proteins could impair the bacterium's ability to adapt to environmental stresses, rendering it more susceptible to host defenses and antimicrobial treatments.

Conclusion

This study provides a comprehensive analysis of the genetic underpinnings of carotenogenesis and light-induced transcriptome remodelling in Mycobacterium kansasii. By elucidating the molecular mechanisms governing these processes, we enhance our understanding of how environmental factors influence bacterial physiology and pathogenicity. Further research in this area could pave the way for innovative approaches to combating infections caused by M. kansasiii and other opportunistic pathogens. Future research should focus on characterizing the functional roles of specific regulatory proteins identified in this study, using genetic knockouts and biochemical assays. Additionally, exploring the interplay between light-induced responses and other environmental factors, such as temperature and nutrient availability, could provide a more holistic understanding of M. kansasiii's adaptability and pathogenicity.