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N uclease A ( Gbs 0661), an extracellular nuclease of S treptococcus agalactiae , attacks the neutrophil extracellular traps and is needed for full virulence
Author(s) -
DerréBobillot Aurélie,
CortesPerez Naima G.,
Yamamoto Yuji,
Kharrat Pascale,
Couvé Elizabeth,
Da Cunha Violette,
Decker Patrice,
Boissier MarieChristophe,
Escartin Frédéric,
Cesselin Bénédicte,
Langella Philippe,
BermúdezHumarán Luis G.,
Gaudu Philippe
Publication year - 2013
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.12295
Subject(s) - virulence , biology , nuclease , streptococcus agalactiae , extracellular , microbiology and biotechnology , neutrophil extracellular traps , mutant , lactococcus lactis , streptococcus , gene , bacteria , biochemistry , genetics , immunology , inflammation , lactic acid
Summary Most bacteria of the genus S treptococcus are opportunistic pathogens, and some of them produce extracellular DNases , which may be important for virulence. Genome analyses of S treptococcus agalactiae ( GBS ) neonate isolate NEM 316 revealed the presence of seven genes putatively encoding secreted DNases , although their functions, if any, are unknown. In this study, we observed that respiration growth of GBS led to the extracellular accumulation of a putative nuclease, identified as being encoded by the gbs0661 gene. When overproduced in L actococcus lactis , the protein was found to be a divalent cation‐requiring, pH ‐stable and heat‐stable nuclease that we named N uclease A ( NucA ). Substitution of the histidine 148 by alanine reduced nuclease activity of the GBS wild‐type strain, indicating that NucA is the major nuclease ex vivo . We determined that GBS is able to degrade the DNA matrix comprising the neutrophil extracellular trap ( NET ). The nucA H148A mutant was impaired for this function, implicating NucA in the virulence of GBS . In vivo infection studies confirmed that NucA is required for full infection, as the mutant strain allowed increased bacterial clearance from lung tissue and decreased mortality in infected mice. These results show that NucA is involved in NET escape and is needed for full virulence.