Structure and function of clostridial phospholipases C

Jepson, Marie; Titball, Richard W.

doi:10.1016/s1286-4579(00)01281-8

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…The availability of the crystal structure for the C. perfringens a-toxin (Naylor et al 1998) and the results from a number of structure-function studies (AlapeGiró n et al 2000; Jepson and Titball 2000;Walker et al 2000;Nagahama et al 2002;Sakurai et al 2004) allow for thorough analysis of recombination involving the plc gene. The a-toxin possesses two domains (Titball et al 1991;Naylor et al 1998).…”

Section: Analysis Of Genetic Variability and Recombinationmentioning

confidence: 99%

Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations

et al. 2006

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Clostridium perfringens is an important human and animal pathogen that causes a number of diseases that vary in their etiology and severity. Differences between strains regarding toxin gene composition and toxin production partly explain why some strains cause radically different diseases than others. However, they do not provide a complete explanation. The purpose of this study was to determine if there is a phylogenetic component that explains the variance in C. perfringens strain virulence by assessing patterns of genetic polymorphism in genes (colA gyrA, plc, pfoS, and rplL) that form part of the core genome in 248 type A strains. We found that purifying selection plays a central role in shaping the patterns of nucleotide substitution and polymorphism in both housekeeping and virulence genes. In contrast, recombination was found to be a significant factor only for the virulence genes plc and colA and the housekeeping gene gyrA. Finally, we found that the strains grouped into five distinct evolutionary lineages that show evidence of host adaptation and the early stages of speciation. The discovery of these previously unknown lineages and their association with distinct disease presentations carries important implications for human and veterinary clostridial disease epidemiology and provides important insights into the pathways through which virulence has evolved in C. perfringens.

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Section: Analysis Of Genetic Variability and Recombinationmentioning

confidence: 99%

Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations

et al. 2006

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“…Although bacterial PLCs are thought to be key virulence factors in several infectious diseases, the pathogenic mechanisms are quite varied. For example, clostridial a-toxin is a PLC with haemolytic and lethal dermonecrotic and platelet-aggregating properties (Jepson & Titball, 2000) whilst that of Listeria monocytogenes functions to allow the organism to escape from intracellular phagolysosomes (Grundling et al, 2003;Smith et al, 1995). Purified PlcH preparations from P. aeruginosa are cytotoxic since injection into mice causes hepatonecrosis and renal tubular necrosis (Meyers et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Characterization of two distinct phospholipase C enzymes from Burkholderia pseudomallei

et al. 2007

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“…Several Clostridium species produce two-domain Zn 2ϩ metalloPLCs, possessing an ␣-helical N-terminal catalytic domain homologous to the B. cereus PLC and an additional Ca 2ϩ -binding C-terminal ␤-sandwich domain similar to mammalian C2 domains (212). The best-characterized clostridial PLC is C. perfringens alpha-toxin ( Fig.…”

Section: Phospholipase Csmentioning

confidence: 99%

“…Muscle has the lowest concentration of complex gangliosides among mammalian tissues, offering a possible explanation for the high susceptibility of muscle fibers to alpha-toxin (223). Other clostridial PLCs with a structure similar to C. perfringens alpha-toxin display lower toxicities due to different amino acid substitutions (212,224).…”

Section: Phospholipase Csmentioning

confidence: 99%

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

Flores-Dı́az

Monturiol-Gross

Naylor

et al. 2016

Microbiol Mol Biol Rev

172

143

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SUMMARYBacterial 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.

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Structure and function of clostridial phospholipases C

Cited by 20 publications

References 34 publications

Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations

Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations

Characterization of two distinct phospholipase C enzymes from Burkholderia pseudomallei

Bacterial Sphingomyelinases and Phospholipases as Virulence Factors

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