The Mycobacterium tuberculosis MmpL11 Cell Wall Lipid Transporter Is Important for Biofilm Formation, Intracellular Growth, and Nonreplicating Persistence
ABSTRACT
The mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The
m
ycobacterial
m
embrane
p
rotein
l
arge (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and
Mycobacterium tuberculosis
pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature consistent with an important role in the basic physiology of the bacterium. MmpL3 is essential and transports trehalose monomycolate to the mycobacterial surface. In this report, we characterize the role of MmpL11 in
M. tuberculosis. M. tuberculosis
mmpL11
mutants have altered biofilms associated with lower levels of mycolic acid wax ester and long-chain triacylglycerols than those for wild-type bacteria. While the growth rate of the
mmpL11
mutant is similar to that of wild-type
M. tuberculosis
in macrophages, the mutant exhibits impaired survival in an
in vitro
granuloma model. Finally, we show that the survival or recovery of the
mmpL11
mutant is impaired when it is incubated under conditions of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell wall lipid substrates are important for survival in the context of adaptive immune pressure and for nonreplicating persistence, both of which are critically important aspects of
M. tuberculosis
pathogenicity.
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