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Surface hydrolysis of sphingomyelin by the outer membrane protein R v0888 supports replication of M ycobacterium tuberculosis in macrophages
Author(s) -
Speer Alexander,
Sun Jim,
Danilchanka Olga,
Meikle Virginia,
Rowland Jennifer L.,
Walter Kerstin,
Buck Bradford R.,
Pavlenok Mikhail,
Hölscher Christoph,
Ehrt Sabine,
Niederweis Michael
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13073
Subject(s) - sphingomyelin , ceramide , biology , sphingomyelin phosphodiesterase , bacterial outer membrane , biochemistry , phosphocholine , microbiology and biotechnology , mutant , intracellular , respiratory burst , escherichia coli , membrane , phospholipid , apoptosis , phosphatidylcholine , gene
Summary Sphingomyelinases secreted by pathogenic bacteria play important roles in host–pathogen interactions ranging from interfering with phagocytosis and oxidative burst to iron acquisition. This study shows that the M tb protein R v0888 possesses potent sphingomyelinase activity cleaving sphingomyelin, a major lipid in eukaryotic cells, into ceramide and phosphocholine, which are then utilized by M tb as carbon, nitrogen and phosphorus sources, respectively. An M tb rv0888 deletion mutant did not grow on sphingomyelin as a sole carbon source anymore and replicated poorly in macrophages indicating that M tb utilizes sphingomyelin during infection. R v0888 is an unusual membrane protein with a surface‐exposed C ‐terminal sphingomyelinase domain and a putative N ‐terminal channel domain that mediated glucose and phosphocholine uptake across the outer membrane in an M . smegmatis porin mutant. Hence, we propose to name R v0888 as SpmT ( sp hingomyelinase of M ycobacterium t uberculosis ). Erythrocyte membranes contain up to 27% sphingomyelin. The finding that R v0888 accounts for half of M tb's hemolytic activity is consistent with its sphingomyelinase activity and the observation that R v0888 levels are increased in the presence of erythrocytes and sphingomyelin by 5‐ and 100‐fold, respectively. Thus, R v0888 is a novel outer membrane protein that enables M tb to utilize sphingomyelin as a source of several essential nutrients during intracellular growth.