Association of Mycobacterium Proteins with Lipid Droplets. J Bacteriol 2018 Aug 15;200(16)
Date
05/16/2018Pubmed ID
29760207Pubmed Central ID
PMC6060360DOI
10.1128/JB.00240-18Scopus ID
2-s2.0-85050494395 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Mycobacterium tuberculosis is a global pathogen of significant medical importance. A key aspect of its life cycle is the ability to enter into an altered physiological state of nonreplicating persistence during latency and resist elimination by the host immune system. One mechanism by which M. tuberculosis facilitates its survival during latency is by producing and metabolizing intracytoplasmic lipid droplets (LDs). LDs are quasi-organelles consisting of a neutral lipid core such as triacylglycerol surrounded by a phospholipid monolayer and proteins. We previously reported that PspA (phage shock protein A) associates with LDs produced in Mycobacterium In particular, the loss or overproduction of PspA alters LD homeostasis in Mycobacterium smegmatis and attenuates the survival of M. tuberculosis during nonreplicating persistence. Here, M. tuberculosis PspA (PspAMtb) and a ΔpspA M. smegmatis mutant were used as model systems to investigate the mechanism by which PspA associates with LDs and determine if other Mycobacterium proteins associate with LDs using a mechanism similar to that for PspA. Through this work, we established that the amphipathic helix present in the first α-helical domain (H1) of PspA is both necessary and sufficient for the targeting of this protein to LDs. Furthermore, we identified other Mycobacterium proteins that also possess amphipathic helices similar to PspA H1, including a subset that localize to LDs. Altogether, our results indicate that amphipathic helices may be an important mechanism by which proteins target LDs in prokaryotes.IMPORTANCEMycobacterium spp. are one of the few prokaryotes known to produce lipid droplets (LDs), and their production has been linked to aspects of persistent infection by M. tuberculosis Unfortunately, little is known about LD production in these organisms, including how LDs are formed, their function, or the identity of proteins that associate with them. In this study, an established M. tuberculosis LD protein and a surrogate Mycobacterium host were used as model systems to study the interactions between proteins and LDs in bacteria. Through these studies, we identified a commonly occurring protein motif that is able to facilitate the association of proteins to LDs in prokaryotes.
Author List
Armstrong RM, Carter DC, Atkinson SN, Terhune SS, Zahrt TCAuthors
Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of WisconsinScott Terhune PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Amino Acid MotifsBacterial Proteins
Heat-Shock Proteins
Lipid Droplets
Lipid Metabolism
Mycobacterium tuberculosis
Phospholipids
Protein Transport
Proteomics
Triglycerides
