Bacteria have evolved a variety of enzymes to eliminate endogenous or host-derived oxidative stress factors. The Dps protein, first identified in
Escherichia coli
, contains a ferroxidase center and protects bacteria from reactive oxygen species damage. There is a lack of knowledge of the role of Dps-like proteins in bacterial pathogenesis.
Actinobacillus pleuropneumoniae
causes pleuropneumonia, a respiratory disease of swine. The
A. pleuropneumoniae
ftpA
gene is up-regulated during a shift to anaerobiosis, in biofilms and, as found in this study, also by H
2
O
2
. An
A. pleuropneumoniae
ftpA
deletion mutant (△
ftpA
) had increased H
2
O
2
sensitivity, less intracellular viability in macrophages, and decreased virulence in a mouse infection model. Expression of
ftpA
in an
E. coli
dps
mutant restored wild-type resistance to H
2
O
2
. FtpA possesses a conserved ferritin domain containing a ferroxidase site. Recombinant rFtpA bound and oxidized Fe
2+
reversibly. Under aerobic conditions, compared with the wild-type strain, the viability of an △
ftpA
mutant was reduced after extended culture, transition from anaerobic to aerobic conditions, and upon supplementation with Fenton reaction substrates. Under anaerobic conditions, additional H
2
O
2
resulted in a more severe growth defect of △
ftpA
than under aerobic conditions. Therefore, by oxidizing and mineralizing Fe
2+
, FtpA alleviates oxidative damage mediated by intracellular Fenton reactions. Furthermore, by mutational analysis, two residues were confirmed to be critical for Fe
2+
binding and oxidization, as well as for
A. pleuropneumoniae
H
2
O
2
resistance. Taken together, this study demonstrates that
A. pleuropneumoniae
FtpA is a Dps-like protein, playing critical roles in oxidative stress resistance and virulence.
IMPORTANCE
As a ferroxidase, Dps of
Escherichia coli
can protect bacteria from reactive oxygen species damage, but its role in bacterial pathogenesis has received little attention. In this study, FtpA of the swine respiratory pathogen
A. pleuropneumoniae
was identified as a new Dps-like protein. It facilitated
A. pleuropneumoniae
resistance to H
2
O
2
, survival in macrophages, and infection
in vivo
. FtpA could bind and oxidize Fe
2+
through two important residues in its ferroxidase site and protected the bacteria from oxidative damage mediated by the intracellular Fenton reaction. These findings provide new insights into the role of the FtpA-based antioxidant system in the pathogenesis of
A. pleuropneumoniae
, and the conserved Fe
2+
binding ligands in Dps/FtpA provide novel drug target candidates for disease prevention.
The role of oxygenation on the attachment of Escherichia coli rpoS mutant under aerobic conditions