An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis

Abstract

Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease.

Assessing a transmission network of Mycobacterium tuberculosis in an African city using single nucleotide polymorphism threshold analysis

“…These genes also have been shown to have sphingomyelinase activity which can catalyze the hydrolysis of sphingomyelin and can interfere with the host inflammatory response aiding the infection (Castro-Garza et al, 2016). Alteration and/or inactivation of those genes as observed in our study isolates could potentially modify virulence to decrease lung damage and prolong a less severe disease stage for the host.…”

“…The plcABCD family of genes encodes a phospholipase C, playing a role in pathogenesis by cleaving phospholipids during intracellular replication and trafficking during acute infection (Talarico et al, 2005). These genes also have been shown to have sphingomyelinase activity which can catalyze the hydrolysis of sphingomyelin and can interfere with the host inflammatory response aiding the infection (Castro‐Garza et al, 2016). Alteration and/or inactivation of those genes as observed in our study isolates could potentially modify virulence to decrease lung damage and prolong a less severe disease stage for the host.…”

Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis

“…Besides, the protein encoded by Rv0169 is located on mycobacterial cell wall with its cell entry epitope flank on the surface (Das et al, 2003 ; Mitra et al, 2005 ) suggesting its role in host-pathogen interactions (Shimono et al, 2003 ). Rv1755c upregulated during intracellular replication of mycobacteria has predicted protein product with virulence function and is involved in the pathogenesis of M. tuberculosis for intracellular survival by altering the cell signaling events or directly causing cytotoxicity to host cells (Castro-Garza et al, 2016 ). Altogether, the upregulation of these transcripts controlling the various metabolic states of mycobacteria reflects the adaptation of M. tuberculosis to host immunity and environmental stresses in different conditions.…”

Diverse Facets of Sphingolipid Involvement in Bacterial Infections

“…These compounds are used by bacteria as the sources of carbon, nitrogen and phosphorus (Speer et al, 2015). However, the purpose of M. tuberculosis -produced sphingomyelinases might be not only to provide a source of nutrients, but to modulate sphingolipid signaling and cell death induction, thereby controlling the immune response to this pathogen (Castro-Garza et al, 2016).…”