Bacterial Sphingomyelinases and Phospholipases as Virulence Factors.
Bacterial sphingomyelinases and phospholipases are a heterogeneous group of esterases which are usually surface associated or secreted by a wide variety of Gram-positive and Gram-negative bacteria. These enzymes hydrolyze sphingomyelin and glycerophospholipids, respectively, generating products identical to the ones produced by eukaryotic enzymes which play crucial roles in distinct physiological processes, including membrane dynamics, cellular signaling, migration, growth, and death. Several bacterial sphingomyelinases and phospholipases are essential for virulence of extracellular, facultative, or obligate intracellular pathogens, as these enzymes contribute to phagosomal escape or phagosomal maturation avoidance, favoring tissue colonization, infection establishment and progression, or immune response evasion. This work presents a classification proposal for bacterial sphingomyelinases and phospholipases that considers not only their enzymatic activities but also their structural aspects. An overview of the main physiopathological activities is provided for each enzyme type, as are examples in which inactivation of a sphingomyelinase- or a phospholipase-encoding gene impairs the virulence of a pathogen. The identification of sphingomyelinases and phospholipases important for bacterial pathogenesis and the development of inhibitors for these enzymes could generate candidate vaccines and therapeutic agents, which will diminish the impacts of the associated human and animal diseases.
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Marietta
M
Flores-Díaz
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Laura
L
Monturiol-Gross
Department of Biological Sciences, Birkbeck College, London, United Kingdom.
Claire
C
Naylor
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica Departamento de Bioquímica, Escuela de Medicina, Universidad de Costa Rica, San José, Costa Rica alberto.alape@ucr.ac.cr fliegera@rki.de.
Alberto
A
Alape-Girón
Division of Enteropathogenic Bacteria and Legionella, Robert Koch-Institut, Wernigerode, Germany alberto.alape@ucr.ac.cr fliegera@rki.de.
Antje
A
Flieger
D001419:Bacteria / Q000201:enzymology / Q000472:pathogenicity*; D000068536:Bacillota / Q000201:enzymology / Q000472:pathogenicity; D005658:Fungi / Q000201:enzymology / Q000472:pathogenicity*; D010739:Phospholipase D / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D020560:Proteobacteria / Q000201:enzymology / Q000472:pathogenicity; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000472:pathogenicity; D010738:Type C Phospholipases / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
D037521:Virulence Factors; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; D010739:Phospholipase D; C055160:sphingomyelin phosphodiesterase D