title: Penicillin-binding proteins in Streptococcus agalactiae: a novel mechanism for evasion of immune clearance.
abstract: Group B streptococci (GBS) remain the most significant bacterial pathogen causing neonatal sepsis, pneumonia and meningitis in the USA despite CDC-recommended chemoprophylaxis strategies for preventing infection. To cause infection pathogens such as GBS must evade recognition and clearance by the host's immune system. Strategies for avoidance of opsonization and phagocytic killing include elaboration of antiopsonophagocytic capsules and surface proteins. During screening for mutants of GBS that were attenuated for virulence in a neonatal rat sepsis model, we identified a mutant with a transposon insertion in the ponA gene. ponA encodes an extra-cytoplasmic penicillin-binding protein PBP1a, a newly identified virulence trait for GBS that promotes resistance to phagocytic killing independent of capsular polysaccharide. Complementation analysis in vivo and in vitro confirmed that the altered phenotypes observed in the mutant were due to the transposon insertion in ponA. Deletion of PBP1a does not affect C3 deposition on GBS suggesting that mechanism by which PBP1a protects GBS from phagocytic killing is distinct from the antiopsonic activity of capsular polysaccharide. This is the first report describing expression of an antiphagocytic surface protein by GBS and represents a novel mechanism for evasion of immune recognition and clearance that may explain the decreased virulence observed in Gram-positive bacterial species for penicillin-binding protein mutants.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Children's Hospital and Regional Medical Center and University of Washington, Seattle, WA 98105, USA. ajones@chmc.org
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Jones
authors.forename: Rachel H V
authors.initials: RH
authors.lastname: Needham
authors.forename: Anne
authors.initials: A
authors.lastname: Clancy
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Knoll
authors.forename: Craig E
authors.initials: CE
authors.lastname: Rubens
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D006602:Hexosyltransferases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000378:metabolism*; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013292:Streptococcus agalactiae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D011135:Polysaccharides, Bacterial; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase