Bordetella pertussis Acetylome is Shaped by Lysine Deacetylase Bkd1

Post-translational
modifications of proteins enable swift physiological
adaptation of cells to altered growth conditions and stress. Aside
from protein phosphorylation, acetylation on ε-amino groups
of lysine residues (N-ε-lysine acetylation)
represents another important post-translational modification of proteins.
For many bacterial pathogens, including the whooping cough agent Bordetella pertussis, the role and extent of protein
acetylation remain to be defined. We expressed in Escherichia
coli the BP0960 and BP3063 genes encoding two putative
deacetylases of B. pertussis and show
that BP0960 encodes a lysine deacetylase enzyme, named Bkd1, that
regulates acetylation of a range of B. pertussis proteins. Comparison of the proteome and acetylome of a Δbkd1 mutant with the proteome and acetylome of wild-type B. pertussis (PRIDE ID. PXD016384) revealed that
acetylation on lysine residues may modulate activities or stabilities
of proteins involved in bacterial metabolism and histone-like proteins.
However, increased acetylation of the BvgA response regulator protein
of the B. pertussis master virulence-regulating
BvgAS two-component system affected neither the total levels of produced
BvgA nor its phosphorylation status. Indeed, the Δbkd1 mutant was not impaired in the production of key virulence factors
and its survival within human macrophages in vitro was not affected. The Δbkd1 mutant exhibited
an increased growth rate under carbon source-limiting conditions and
its virulence in the in vivo mouse lung infection
model was somewhat affected. These results indicate that the lysine
deacetylase Bkd1 and N-ε-lysine acetylation
primarily modulate the general metabolism rather than the virulence
of B. pertussis.