Mycobacterium tuberculosis Uses Mce Proteins to Interfere With Host Cell Signaling

Abstract

Tuberculosis continues to be the main cause for mortality by an infectious agent, making Mycobacterium tuberculosis one of the most successful pathogens to survive for long durations within human cells. In order to survive against host defenses, M. tuberculosis modulates host cell signaling. It employs many proteins to achieve this and the Mce proteins are emerging as one group that play a role in host cell signaling in addition to their primary role as lipid/sterol transporters. Mce proteins belong to the conserved Mce/MlaD superfamily ubiquitous in diderm bacteria and chloroplasts. In mycobacteria, mce operons, encode for six different Mce proteins that assemble with inner membrane permeases into complexes that span across the mycobacterial cell wall. Their involvement in signaling modulation is varied and they have been shown to bind ERK1/2 to alter host cytokine expression; eEF1A1 to promote host cell proliferation and integrins for host cell adherence and entry. Recently, structures of prokaryotic Mce/MlaD proteins have been determined, giving an insight into the conserved domain. In this mini-review, we discuss current evidence for the role of mycobacterial Mce proteins in host cell signaling and structural characteristics of the protein-protein interactions coordinated by the human proteins to modulate the host signaling.

Genomic Virulence Features of Two Novel Species Nocardia barduliensis sp. nov. and Nocardia gipuzkoensis sp. nov., Isolated from Patients with Chronic Pulmonary Diseases

“…The genomes of isolates 335427 T and 234509 T contained 167 and 154 genes, respectively, encoding for virulence factor proteins, including those involved in adherence to the host cells ( Figure 2 ). In this context, the mce proteins which were found on the mycobacterial cell surface and found to play a role in invading the host cell during infection were also detected in Nocardia species [ 72 ]. Isolate 335427 T presented the complete mce operons 5, 7 and 9, while isolate 234509 T had operons 7 and 6.…”

“…Isolate 335427 T presented the complete mce operons 5, 7 and 9, while isolate 234509 T had operons 7 and 6. All the operons showed identical genes: two inner membrane permeases YrbEa and YrbEb and six mceA-F integral membrane proteins [ 72 , 73 ]. In contrast, the closest phylogenetic species N. asiatica NBRC 100129 T was devoid of any mce operon on its draft genome sequence unlike N. abscessus NBRC 100374 T which had operons 5, 6 and 7.…”

Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference

“…Proteins encoded by mce genes have been described to interfere with host cell signaling and it has been shown that mutation of these genes affects M . tuberculosis virulence in mice [ 36 , 37 ]. Also, the expression of two metabolic genes and their regulator namely prpD , prpC and prpR (enoding methylcitrate dehydratase, methylcitrate synthase and their transcriptional regulator, respectively; Fig 4C ) were decreased in AF2122:: pknH TB relative to WT.…”

Lipoproteins in Gram-Positive Bacteria: Abundance, Function, Fitness

“…Four closely related ATP-binding cassette (ABC) transporter-like complexes called Mce are responsible for the import ( Wilburn et al, 2018 ). Three of the Mce proteins represent Lpp ( Fenn et al, 2019 ). Mce proteins are involved in modulating host cell signaling and allow the growth with cholesterol as sole C-source.…”