Comparative in silico analysis of mce operons across Mycobacteriaceae and Nocardiaceae: Insights into genetic arrangements and regulatory mechanisms
摘要
The mammalian cell entry (Mce) proteins are critical for the entry and persistence of Mycobacterium tuberculosis (Mtb) within alveolar macrophages. These proteins assemble into an ATP-binding cassette transporter comprising six substrate-binding proteins (MceA-F), two transmembrane domains (YrbEAB), and two nucleotide-binding domains (MceG2). Although Mtb harbours four distinct mce operons, the regulatory mechanisms governing differential operon expression remain insufficiently understood. In this study, we analyzed the genetic organization, regulatory features, and functional roles of operons encoding Mce proteins across two bacterial families, utilizing a comparative sequence-based approach. Our results reveal a conserved operonic arrangement, and the gene neighbourhood trends further establish the involvement of Mce proteins in cholesterol uptake. Notably, the presence of transcriptional regulators, translational coupling mechanisms, conserved gene clusters encoding translation machinery and accessory proteins suggests a complex, multi-layered regulatory network controlling mce operon expression. Thus, this study offers key computational insights into the complex regulatory framework of the Mce system while also outlining potential experimental approaches to validate the proposed hypotheses.