Expression of the lipopolysaccharide-modifying enzymes PagP and PagL modulates the endotoxic activity of Bordetella pertussis.
Lipopolysaccharide (LPS) is one of the major constituents of the gram-negative bacterial cell envelope. Its endotoxic activity causes the relatively high reactogenicity of whole-cell vaccines. Several bacteria harbor LPS-modifying enzymes that modulate the endotoxic activity of the LPS. Here we evaluated whether two such enzymes, i.e., PagP and PagL, could be useful tools for the development of an improved and less reactogenic whole-cell pertussis vaccine. We showed that expression of PagP and PagL in Bordetella pertussis leads to increased and decreased endotoxic activity of the LPS, respectively. As expected, PagP activity also resulted in increased endotoxic activity of whole bacterial cells. However, more unexpectedly, this was also the case for PagL. This paradoxical result may be explained, in part, by an increased release of LPS, which we observed in the PagL-expressing cells.
Geurtsen
Jeroen
J
Netherlands Vaccine Institute, P.O. Box 457, 3720 AL Bilthoven, The Netherlands.
Steeghs
Liana
L
Hamstra
Hendrik-Jan
HJ
Ten Hove
Jan
J
de Haan
Alex
A
Kuipers
Betsy
B
Tommassen
Jan
J
van der Ley
Peter
P
D000215:Acylation; D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001886:Bordetella pertussis / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D002240:Carbohydrate Sequence; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics; D010566:Virulence Factors, Bordetella / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*
D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D010566:Virulence Factors, Bordetella; C084764:pertussis endotoxin; D004492:Edetic Acid; D000217:Acyltransferases; D002265:Carboxylic Ester Hydrolases