Chlorite
dismutases (Clds) convert chlorite to O2 and
Cl–, stabilizing heme in the presence of strong
oxidants and forming the O=O bond with high efficiency. The
enzyme from the pathogen Klebsiella pneumoniae (KpCld) represents a subfamily of Clds that share most of
their active site structure with efficient O2-producing
Clds, even though they have a truncated monomeric structure, exist
as a dimer rather than a pentamer, and come from Gram-negative bacteria
without a known need to degrade chlorite. We hypothesized that KpCld, like others in its subfamily, should be able to make
O2 and may serve an in vivo antioxidant
function. Here, it is demonstrated that it degrades chlorite with
limited turnovers relative to the respiratory Clds, in part because
of the loss of hypochlorous acid from the active site and destruction
of the heme. The observation of hypochlorous acid, the expected leaving
group accompanying transfer of an oxygen atom to the ferric heme,
is consistent with the more open, solvent-exposed heme environment
predicted by spectroscopic measurements and inferred from the crystal
structures of related proteins. KpCld is more susceptible
to oxidative degradation under turnover conditions than the well-characterized
Clds associated with perchlorate respiration. However, wild-type K. pneumoniae has a significant growth advantage in the
presence of chlorate relative to a Δcld knockout
strain, specifically under nitrate-respiring conditions. This suggests
that a physiological function of KpCld may be detoxification
of endogenously produced chlorite.
This study has reiterated the role of plasmids as bearers of the vast majority of resistance genes in this species and has provided valuable insights into the vital role played by ISs, transposons and integrons in shaping the resistance-coding regions in this important strain. The 'resistance-disarmed' K. pneumoniae ST11 strain generated in this study will offer a more benign and readily genetically modifiable model organism for future extensive functional studies.
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