Characterization of a quinol peroxidase mutant inAggregatibacter actinomycetemcomitans

Abstract

Aggregatibacter actinomycetemcomitans is an oral pathogen causing localized aggressive periodontitis (LAP). Recently, we characterized for the first time a quinol peroxidase (QPO) that catalyzes peroxidase activity using quinol in the respiratory chain of A. actinomycetemcomitans for the reduction of hydrogen peroxide. In the present study, we characterized the phenotype of a QPO null mutant. The QPO null mutant shows an oxidative stress phenotype, suggesting that QPO plays a certain role in scavenging endogenously generated reactive oxygen species. Notably, we discovered that the QPO null mutant exhibits a production defect of leukotoxin (LtxA), which is a secreted bacterial toxin and is known to target human leukocytes and erythrocytes. This result suggests that QPO would be considered as a potential drug target to inhibit the expression of LtxA from A. actinomycetemcomitans for the treatment and prevention of LAP.

Physiological Importance of Cytochrome <i>c</i> Peroxidase in Ethanologenic Thermotolerant <i>Zymomonas mobilis</i>

“…Hydropathy analysis revealed that there is one possible membrane-spanning segment at the N-terminal (data not shown), which is responsible for association with the inner membrane. Although the N-terminal about 20-amino-acid sequence has a character of basic amino acids followed by a hydrophobic sequence, similar to that of a signal sequence, it may be not removed because a similar sequence is present in purified tri-heme CCP in A. actinomycetemcomitans [Yamada et al, 2007;Takashima et al, 2008]. This is consistent with the finding that most peroxidase activity in Z. mobilis was recovered in membrane fractions (see below).…”

“…Structural comparison with other CCPs including the extensively analyzed ubiquinol peroxidase of A. actinomycetemcomitans [Yamada et al, 2007;Takashima et al, 2008] suggests that Z. mobilis ZmCytC is a membranebound peroxidase with three heme c -binding motifs. ZmCytC-dependent peroxidase activity was detected in membrane fractions when ubiquinol or NADH, but not reduced horse heart cytochrome c , was used as an electron donor.…”

“…ZmCytC in Z. mobilis has been annotated as CCP [Seo et al, 2005], though it seems to possess three heme cbinding motifs similar to ubiquinol peroxidase in A. actinomycetemcomitans [Yamada et al, 2007;Takashima et al, 2008]. In order to determine the physiological function of ZmCytC and its electron donor, ZmcytC -disrupted mutant was constructed and examined.…”

“…They bear an N-terminal extension with a heme c -binding motif (CXXCH) and a putative methionine ligand [Atack and Kelly, 2007]. The tri-heme CCP in Actinomyces actinomycetemcomitans has been demonstrated to be a quinol peroxidase based on evidence that it utilizes reduced ubiquinone-1 as an electron donor for the reduction of H 2 O 2 to water [Yamada et al, 2007;Takashima et al, 2008].…”

Quorum sensing of Streptococcus mutans is activated by Aggregatibacter actinomycetemcomitans and by the periodontal microbiome

“…5d) and expression of chaperones and heat shock proteins was up-regulated in the 24 h old co-culture. Quinol peroxidase [42] was most strongly (22-fold) induced in both 8 and 24 h co-culture biofilms (Fig. 5e).…”