The Actinobacterial mce Operon: Structure and Functions

Abstract

The results of studies on mce operons of the causative agent Mycobacterium tuberculosis and actinobacteria are summarized. Mce transporters belong to a group of cell-wall proteins. The genome of M. tuberculosis contains four mce operons that encode complexes, each of which consists of two integral membrane proteins (YrbEB) followed by six other Mce proteins (MceA-F). These proteins are functionally similar to ABC transporters. Despite their significant role in the pathogenesis of M. tuberculosis infection, Mce proteins remain poorly studied due to their complex structure and operon regulation. However, a number of their functions have been characterized; they include the penetration of host cells by M. tuberculosis and its survival, as well as the transport of cholesterol and mycolic acids, which are pathogenicity factors of no small importance. The expression of mce operons depends on many factors, such as the growth phase, the culture medium, and the localization of M. tuberculosis infection. Today, strains of M. tuberculosis and M. bovis with deleted mce operons are considered candidates for the development of new attenuated vaccines that might one day replace the M. bovis BCG vaccine, which is no longer deemed strong enough to hold back the tuberculosis epidemic.

Structure of an endogenous mycobacterial MCE lipid transporter

“…In particular, the Mammalian Cell Entry (MCE) family of proteins has been implicated in the import of substrates such as fatty acids [4][5][6][7] and cholesterol 1,4,8 across the cell envelope of Mtb and related species such as Mycobacterium smegmatis (Msmeg) (Fig. 1a) 3,13,14 . MCE proteins are critical for virulence in Mtb and other bacterial pathogens 1,3,[15][16][17][18][19] , underscoring their fundamental importance for nutrient acquisition from the host.…”

“…Each cluster has a core module of eight conserved genes: 1) two yrbE genes encoding the transmembrane subunits of an ATP-binding-cassette (ABC) transporter and 2) six genes encoding MCE proteins. A variable number of "accessory" proteins are often found adjacent to the eight-gene core module 13 . Additional proteins encoded elsewhere in the genome are also required for Mtb MCE transporter function, including an ATPase, MceG 1,30 , and an integral membrane protein, LucA 4,5 .…”

Structure of an endogenous mycobacterial MCE lipid transporter

“…In particular, the Mammalian Cell Entry (MCE) family of proteins has been implicated in the import of substrates such as fatty acids [4][5][6][7] and cholesterol 1,4,8 across the cell envelope of Mtb and related species such as Mycobacterium smegmatis (Msmeg) (Fig. 1a) 3,13,14 . MCE proteins are critical for virulence in Mtb and other bacterial pathogens 1,3,[15][16][17][18][19] , underscoring their fundamental importance for nutrient acquisition from the host.…”

“…The Mammalian Cell Entry (MCE) proteins are important virulence factors (2,(9)(10)(11)(12)(13)(14) and have been implicated in the import of substrates such as fatty acids (15)(16)(17)(18), and cholesterol (2,15,19) across the cell envelope of Mtb and related species such as Mycobacterium smegmatis (Msmeg) (Fig. 1A) (9,20,21).…”

“…Each cluster has a core module of eight conserved genes: 1) two yrbE genes encoding the transmembrane subunits of an ATP-binding-cassette (ABC) transporter and 2) six genes encoding MCE proteins. A variable number of “accessory” proteins are often found adjacent to the eight-gene core module ( 20 ). Additional proteins encoded elsewhere in the genome are also required for Mtb MCE transporter function, including an ATPase, MceG ( 2, 22 ), and an integral membrane protein, LucA ( 15, 16 ).…”