Understanding and exploiting the Mce proteins from Streptomyces

  • Emily Addington

Student thesis: Doctoral Thesis

Abstract

Streptomyces are Gram-positive bacteria which are typically non-pathogenic saprophytes present in great abundance in soil. This genus is a member of the Actinobacteria phyla, which contains notable pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis in humans.Mammalian cell entry (mce) genes, originally discovered in M. tuberculosis as factors which enabled bacterial entry into human cells, have been identified wildly throughout Actinobacteria, in both pathogenic and non-pathogenic species. Bioinformatic analysis suggests all Actinobacterial operons descend from a singular ancestral operon which underwent proliferation and duplication with minimal gene reshuffling. In many Actinobacteria, mce operons have now been characterised as ABC transporters for lipids.The genome of Streptomyces coelicolor encodes one copy of the mce operon which shares significant homology with the four mce operons of M. tuberculosis, known to be vital for the bacterium’s virulence and persistence within hosts. Within M. tuberculosis, mce1 and mce4 encode ABC transporters for fatty acids and cholesterol respectively.This thesis explores the function of the singular mce operon of S. coelicolor through knockout of the cluster and subsequent phenotypic analysis. Results from this work strongly suggest that the mce operon of S. coelicolor encodes an ABC transporter for sterol import which likely facilitates bacterial survival in the highly competitive rhizosphere. Further results demonstrate that deletion of the mce operon has profound effect on spore resistance, as well as on rate of sporulation and germination, and impacts interaction of the bacterium with soil protists.
Date of Award4 Feb 2022
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsEPSRC (Engineering and Physical Sciences Research Council)
SupervisorPaul Hoskisson (Supervisor) & Katherine Duncan (Supervisor)

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