PubMed Health⌕ Search

Biomedical subjects

Mariko Naito

Publications and source records attributed to Mariko Naito.

At least 19 recordsLinked to original sources
PubMed2006

Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy.

BACKGROUND: Various single nucleotide polymorphisms (SNPs) have explained the association between Helicobacter pylori (H. pylori) and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. METHODS: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345) was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. RESULTS: The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI): 0.08-0.71). Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40). Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90) relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66). Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. CONCLUSIONS: This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These findings require confirmation in much larger studies.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population.

AIM: To examine the association of inducible nitric oxide synthase (iNOS) C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity. METHODS: A single nucleotide polymorphism of iNOS C150T was examined for 454 Japanese health checkup examinees (126 males and 328 females) aged 35 to 85 years without a history of cancer and 202 gastric cancer patients (134 males and 68 females) aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma. RESULTS: The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio (OR) of the C/T + T/T for gastric cancer was increased without statistical significance (OR = 1.19, 95% confidence interval (CI): 0.68-2.08). In the differentiated subgroup (n = 113), however, the OR of the C/T genotype for gastric cancer was significant (OR = 2.02, 95% CI: 1.04-3.92) relative to the C/C genotype. In addition, considering the location of gastric cancer (n = 105), there were significant differences between the controls and non-cardia group with the OR of 2.13 (95% CI: 1.08-4.18) for C/T and 1.94 (95% CI: 1.00-3.78) for C/T + T/T. CONCLUSION: The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancer in a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

Adult↗
PubMed2006

Eradication rate of Helicobacter pylori according to genotypes of CYP2C19, IL-1B, and TNF-A.

BACKGROUND: Lansoprazole, amoxicillin, and clarithromycin are commonly used drugs for eradication of Helicobacter pylori (H. pylori). A few studies reported that the eradication rate was influenced by the functional polymorphism of CYP2C19, whose product metabolizes proton pomp inhibitors including lansoprazole. METHODS: This study examined the eradication rate among 67 participants in the polymorphism study who visited Daiko Medical Center, Nagoya University from July 2004 to October 2005. The participants aged 20 to 69 years were classified into three group according to CYP2C19 genotype; rapid metabolizers (RM) with *1*1 genotype, intermediate metabolizers (IM) with *1*2 or *1*3 genotype, and poor metabolizers (PM) with *2*2, *2*3, or *3*3 genotype. For the genotype classification, G681A (681G for *1 and 681A for *2) and G636A (636G for *1 and 636A for *3) were genotyped by PCR with confronting two-pair primers (PCR-CTPP). They were also genotyped for IL-1B T-31C and TNF-A T-1031C by a duplex PCR-CTPP. RESULTS: The eradication rate was 70.0% for RM, 93.9% for IM, and 85.7% for PM. The difference in the rate between RM and IM+PM was statistically significant (p=0.025). The eradication rate was highest for those with IL-1B -31CC; the p value was marginal among the whole subjects (chi2=3.78, p=0.05) and not significant among the RM group (chi2=1.60, p=0.21). The genotypes of TNF-A T-1031C had no associations with the eradication rate. But among the RM group, the odd ratio (OR) of the TNF-A CT for the eradication rate relative to TT was marginally reduced (OR=0.05, 95% confidence interval, 0.002-1.19). CONCLUSIONS: The present study confirmed the low eradication rate for RM. The reproduced finding provides evidence that the CYP2C19 genotype is useful to predict the success of the treatment. For the RM group, alternative regimens expected to be with a higher eradication rate will be recommended, especially to those with the TNF-A -1031C allele.

Journal Article↗
PubMed2006

Genetic factors involved in the development of Helicobacter pylori-related gastric cancer.

Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL-1B (C-31T or tightly linked T-511C), and TNF-A (T-1031C and C-857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin-associated gene A (PTPN11 A/G at intron 3) and to T-cell responses (IL-2 T-330G and IL-13 C-1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well-documented risk factors. In past case-control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori-related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori-related or -unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori-related. In order to elucidate the genetic traits of H. pylori-related gastric cancer, stepwise evaluation will be required.

Genetic Predisposition to Disease↗
PubMed2006

Periodontal disease and atherosclerosis from the viewpoint of the relationship between community periodontal index of treatment needs and brachial-ankle pulse wave velocity.

BACKGROUND: It has been suggested that periodontal disease may be an independent risk factor for the development of atherosclerosis. However, the relationship between periodontal disease and atherosclerosis has not been fully elucidated. This study aimed to assess the effects of periodontal disease on atherosclerosis. METHODS: The study design was a cross-sectional study. Subjects were 291 healthy male workers in Japan. We used the Community Periodontal Index of Treatment Needs (CPITN) score, average probing depth and gingival bleeding index (rate of bleeding gums) to assess the severity of periodontal disease. We also used the Brachial-Ankle Pulse Wave Velocity (baPWV) as the index for the development of atherosclerosis. RESULTS: The unadjusted odds ratio (OR) of atherosclerosis in relation to the CPITN score was 1.41 [95% CI: 1.16-1.73]. However, after adjustment for age, systolic blood pressure and smoking, the CPITN score had no relationship with atherosclerosis (adjusted OR: 0.91 [0.68-1.20]). CONCLUSION: Our results show no relationship between mild periodontal disease and atherosclerosis after appropriate adjustments.

Adult↗
PubMed2006

Superoxide dismutase-encoding gene of the obligate anaerobe Porphyromonas gingivalis is regulated by the redox-sensing transcription activator OxyR.

Inspection of the genomic DNA sequence of the oral anaerobe Porphyromonas gingivalis reveals that the micro-organism possesses the peroxide-sensing transcription activator OxyR, but not the superoxide-sensing transcription factor SoxR. Investigatation of oxidative-stress-responsive proteins in P. gingivalis by two-dimensional gel electrophoresis showed that two proteins were predominantly upregulated in oxidative conditions. In a P. gingivalis oxyR mutant these two proteins were not induced by treatment with hydrogen peroxide under aerobic conditions. By N-terminal amino acid sequencing, the two proteins were found to be superoxide dismutase and alkyl hydroperoxide reductase, encoded by sod and ahpC, respectively. Northern blot and lacZ fusion analyses revealed that P. gingivalis sod and ahpC were positively regulated by OxyR. Primer extension analysis located the promoter regions of sod and ahpC, and putative -35 boxes of these promoters were found immediately adjacent to their putative OxyR-binding sequences. Moreover, the promoter regions of sod and ahpC had the ability to bind P. gingivalis OxyR protein. These results demonstrate that P. gingivalis sod is one of the OxyR regulons, suggesting that OxyR functions as an intracellular redox sensor rather than a peroxide sensor in this organism. A sod gene of Bacteroides fragilis, which is taxonomically related to P. gingivalis, is inducible by redox stresses but not controlled by its OxyR. A DNA fragment including the B. fragilis sod promoter region could bind the P. gingivalis OxyR protein; however, a putative OxyR binding sequence within the DNA fragment was 14 bases distant from a putative -35 box of its promoter.

Adaptation, Physiological↗
PubMed2006

Gingipains inactivate a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling.

Arginine-specific gingipain and lysine-specific gingipain are two major cysteine proteinases produced by Porphyromonas gingivalis. To clarify the role of gingipains in the interaction between P. gingivalis and the innate immune system, CHO reporter cells expressing TLR2 or TLR4 were stimulated with wildtype or gingipain-deficient P. gingivalis cells and activation of nuclear factor-kappaB in these cells was examined. While CHO/CD14 cells and 7.19 cells, an MD-2-defective mutant derived from CHO/CD14 cells, failed to respond to wild-type P. gingivalis, they responded to gingipain-deficient P. gingivalis. On the other hand, CHO/CD14/TLR2 cells responded to both wild-type and gingipain-deficient P. gingivalis. These results suggested that gingipains have no effects on TLR2-dependent signaling from P. gingivalis but have inhibitory effects on TLR2-and TLR4-independent signaling in CHO cells. Indeed, the activity of gingipain-deficient P. gingivalis to induce the activation of 7.19 cells was diminished after treatment of the bacterial cells with gingipains. We next partially purified bacterial cell components activating 7.19 cells from gingipain-deficient P. gingivalis. The activity of the partially purified components was diminished by treatment with heat or gingipains. It is also noteworthy that anti-CD14 mAb inhibited the activation of 7.19 cells induced by the partially purified components. These results indicated that the components of P. gingivalis that were able to induce TLR2-and TLR4-independent signaling were inactivated by gingipains before being recognized by CD14. The inactivation of the components would be helpful for P. gingivalis to escape from the innate immune system.

Adhesins, Bacterial↗
PubMed2006

Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase.

Evidence from recent epidemiological studies suggests a link between periodontal infections and increased risk of atherosclerosis and related cardiovascular and cerebrovascular events in human subjects. One of the major pathogens of periodontitis, Porphyromonas gingivalis, has the ability to aggregate human platelets in platelet-rich plasma (PRP). Mechanism of P. gingivalis-induced platelet aggregation in PRP was investigated. Proteinase inhibitors toward Arg-gingipain (Rgp) and Lys-gingipain (Kgp) did not suppress P. gingivalis-induced platelet aggregation in PRP, whereas the Rgp inhibitor markedly inhibited P. gingivalis-induced platelet aggregation using washed platelets. Mutant analysis revealed that P. gingivalis-induced platelet aggregation in PRP depended on Rgp-, Kgp- and haemagglutinin A (HagA)-encoding genes that intragenically coded for adhesins such as Hgp44. Hgp44 adhesin on the bacterial cell surface, which was processed by Rgp and Kgp proteinases, was essential for P. gingivalis-induced platelet aggregation in PRP. P. gingivalis cell-reactive IgG in plasma, and FcgammaRIIa receptor and to a lesser extent GPIbalpha receptor on platelets were found to be a prerequisite for P. gingivalis-induced platelet aggregation in PRP. These results reveal a novel mechanism of platelet aggregation by P. gingivalis.

Adhesins, Bacterial↗
PubMed2006

Linguistic adaptation and validation of the General Oral Health Assessment Index (GOHAI) in an elderly Japanese population.

OBJECTIVES: This study sought to develop a Japanese version of the General Oral Health Assessment Index (GOHAI) and validate its use in an elderly Japanese population. METHODS: The GOHAI scale was translated in a standardized way consisting of forward translation, pilot study, and backward translation. Psychometric properties of the final version were assessed on 175 participants (mean age: 70.0 years, SD 6.4). RESULTS: The response rate was more than 98% for each item. The reliability in terms of a Cronbach's alpha value was 0.89. The mean GOHAI scores were significantly lower for participants with poor perceived oral health (P<0. 001) or poor perceived general health (P<0.01). Significant correlations were observed between the GOHAI scores and the general health or physical functioning scores of the Medical Outcome Study Short Form 36 (P<0.01). CONCLUSIONS: The present study showed that the Japanese version of the GOHAI was psychometrically valid in an elderly sample population.

Aged↗
PubMed2006

The hemoglobin receptor protein of porphyromonas gingivalis inhibits receptor activator NF-kappaB ligand-induced osteoclastogenesis from bone marrow macrophages.

Extracellular proteinaceous factors of Porphyromonas gingivalis, a periodontal pathogen, that influence receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced osteoclastogenesis from bone marrow macrophages were investigated. The culture supernatant of P. gingivalis had the ability to inhibit RANKL-induced in vitro osteoclastogenesis. A major protein of the culture supernatant, hemoglobin receptor protein (HbR), suppressed RANKL-induced osteoclastogenesis in a dose-dependent fashion. HbR markedly inhibited RANKL-induced osteoclastogenesis when present in the culture for the first 24 h after addition of RANKL, whereas no significant inhibition was observed when HbR was added after 24 h or later, implying that HbR might interfere with only the initial stage of RANKL-mediated differentiation. HbR tightly bound to bone marrow macrophages and had the ability to induce phosphorylation of ERK, p38, NF-kappaB, and Akt. RANKL-induced phosphorylation of ERK, p38, and NF-kappaB was not suppressed by HbR, but that of Akt was markedly suppressed. HbR inhibited RANKL-mediated induction of c-Fos and NFATc1. HbR could induce beta interferon (IFN-beta) from bone marrow macrophages, but the induction level of IFN-beta might not be sufficient to suppress RANKL-mediated osteoclastogenesis, implying presence of an IFN-beta-independent pathway in HbR-mediated inhibition of osteoclastogenesis. Since rapid and extensive destruction of the alveolar bone causes tooth loss, resulting in loss of the gingival crevice that is an anatomical niche for periodontal pathogens such as P. gingivalis, the suppressive effect of HbR on osteoclastogenesis may help the microorganism exist long in the niche.

Animals↗
PubMed2006

Two new criteria of the metabolic syndrome: prevalence and the association with brachial-ankle pulse wave velocity in Japanese male workers.

In 1998 and 2001, The World Health Organization and the National Cholesterol Education Program Adult Treatment Panel III proposed working criteria for the metabolic syndrome (MS), but they are not perfect for use in diverse ethnicities. In 2005, the International Diabetes Federation (IDF) and eight societies in Japan respectively proposed new criteria. However, there has been no report regarding the application of these new criteria in Japanese workplaces. We conducted a cross-sectional study of 377 healthy Japanese men aged 20-64 yr who worked in a chemical factory in Kanagawa, Japan. Participants completed a self-reported questionnaire, underwent a physical examination including waist measurements and brachial-ankle pulse wave velocity (baPWV), and provided overnight fasting blood samples. The prevalence of MS in Japanese men was 17.0% and 13.5% according to the new IDF and Japanese criteria respectively. In both of the new criteria, baPWV was significantly higher in those with MS than those without MS (1,563 +/- 264.2 vs 1,362 +/- 204.6 cm/sec, p<0.001 in the new IDF criterion; 1,574 +/- 265.2 vs 1,368 +/- 209.1 cm/sec, p<0.001 in the Japanese criterion). In the analysis of the 5 or 6 subgroups stratified according to the number of MS components, baPWV increased significantly with increasing number of MS components (p for trend<0.01 in both criteria). The new IDF and Japanese criterion are both good for diagnosing MS among Japanese because a linear increase in baPWV occurred with increasing MS components after adjustment for potential confounding factors. Further studies are expected using these new criteria.

Adult↗
PubMed2006

Alternative genotyping method of GSTT1 null/present polymorphism.

Glutathione S-transferase (GST) theta is an enzyme to detoxify xenobiotic compounds. The gene GSTT1 has a null/present polymorphism in one of the targets for cancer susceptibility research. The polymorphism is classified into two types: present type with at least one present allele (heterozygote and homozygote) and null type without a present allele. Although one report showed a method to distinguish the heterozygote from the present homozygote, its use has been limited possibly owing to the difficulty of successful genotyping of long DNA sequences (1460 base pairs). This article reports an alternative method utilizing typical PCR primers specific to the null allele (566 base pairs) and the present allele (458 base pairs). All samples of the GSTT1 null genotype processed by the present PCR method (n = 331), were correctly classified as the null genotype by a conventional method, and the samples of heterozygous (n = 364) or present homozygous (n = 108) genotype as the present genotype; this indicates that it is appropriate for future research to utilize three genotypes of the GSTT1 null/present polymorphism.

Disease↗
PubMed2006

Oral health status and health-related quality of life: a systematic review.

This study was conducted in order to identify the literature on oral health status and health-related QOL, review the findings systematically, and assess the association between them. We performed a literature search of reports published between January 1973 and June 2004, using five databases including MEDLINE. Only studies that used validated generic health-related QOL instruments were selected. The reviewers evaluated selected articles independently and resolved disagreements by consensus. A total of 1,726 articles were retrieved and seven were selected for the review; five observational studies and two intervention studies. Four studies showed significant associations between oral health status and health-related QOL. Temporomandibular disorders were highly associated with reduced health-related QOL. Poor oral status linked to both craniomandibular and cervical spinal pain was associated with increased impairment of health-related QOL. Dissatisfaction with the teeth and mouth, and a sensation of dry mouth contributed to reduce health-related QOL. Providing edentulous patients with implant-supported full dentures contributed to improve health-related QOL. Assessment of health-related QOL in relation to oral health with validated instruments remains insufficient. The present findings suggest that oral health status could affect health-related QOL in some settings; however, further evidence is needed to support this interpretation.

Craniomandibular Disorders↗
PubMed2005

Novel recombinant BCG and DNA-vaccination against tuberculosis in a cynomolgus monkey model.

We have developed two novel tuberculosis (TB) vaccines: a DNA vaccine combination expressing mycobacterial heat shock protein 65 (Hsp65) and interleukin-12 (IL-12) by using the hemagglutinating virus of Japan (HVJ)-liposome (HSP65+IL-12/HVJ) and a recombinant BCG harboring the 72f fusion gene (72f rBCG). These vaccines provide remarkable protective efficacy in mouse and guinea pig models, as compared to the current by available BCG vaccine. In the present study, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis, to evaluate the HSP65+IL-12/HVJ and 72f rBCG vaccines. Vaccination with HSP65+IL-12/HVJ as well as 72f rBCG vaccines provided better protective efficacy as assessed by the Erythrocyte Sedimentation Rate, chest X-ray findings and immune responses than BCG. Most importantly, HSP65+IL-12/HVJ resulted in an increased survival for over a year. This is the first report of successful DNA vaccination and recombinant BCG vaccination against M. tuberculosis in the monkey model.

Animals↗
PubMed2005

Identification of a new membrane-associated protein that influences transport/maturation of gingipains and adhesins of Porphyromonas gingivalis.

The dual membrane envelopes of Gram-negative bacteria provide two barriers of unlike nature that regulate the transport of molecules into and out of organisms. Organisms have developed several systems for transport across the inner and outer membranes. The Gram-negative periodontopathogenic bacterium Porphyromonas gingivalis produces proteinase and adhesin complexes, gingipains/adhesins, on the cell surface and in the extracellular milieu as one of the major virulence factors. Gingipains and/or adhesins are encoded by kgp, rgpA, rgpB, and hagA on the chromosome. In this study, we isolated a P. gingivalis mutant (porT), which showed very weak activities of gingipains in the cell lysates and culture supernatants. Subcellular fractionation and immunoblot analysis demonstrated that precursor forms of gingipains and adhesins were accumulated in the periplasmic space of the porT mutant cells. Peptide mass fingerprinting and N-terminal amino acid sequencing of the precursor proteins and the kgp'-'rgpB chimera gene product in the porT mutant indicated that these proteins lacked the signal peptide regions, consistent with their accumulation in the periplasm. The PorT protein seemed to be membrane-associated and exposed to the periplasmic space, as revealed by subcellular fractionation and immunoblot analysis using anti-PorT antiserum. These results suggest that the membrane-associated protein PorT is essential for transport of the kgp, rgpA, rgpB, and hagA gene products across the outer membrane from the periplasm to the cell surface, where they are processed and matured.

Adhesins, Bacterial↗
PubMed2005

Possible interactions of the endothelial constitutive nitric oxide synthase genotype with alcohol drinking and walking time for high serum uric acid levels among Japanese.

A variable number of tandem repeat polymorphism located in intron 4 of the gene for endothelial constitutive nitric oxide synthase (ecNOS) is reported to be significantly associated with the nitric oxide level, which influences serum uric acid (SUA). To cast light on any association between the polymorphism and hyperuricemia, as well as gene-environment interactions, a cross-sectional study was conducted for 703 health checkup examinees (213 men and 490 women). The age-adjusted odds ratio (aOR) of hyperuricemia (> or =7 mg/dL) for ecNOS 4/4, 4/5, or 5/6 genotypes (non-5/5 group) as compared with the 5/5 genotype was 2.41 (95% confidence interval [CI], 1.09-5.30) in men. The aORs for drinking alcohol relative to never drinking were found to be 8.93 (95% CI, 1.02-78.16) among men with non-5/5 genotypes and 1.76 (95% CI, 0.59-5.26) for their 5/5 counterparts. Moreover, the aORs for heavy drinking (> or =50 mL/d) were 23.16 (95% CI, 2.14-250.35) and 2.48 (95% CI, 0.75-8.15), respectively. The interaction between the genotype and current drinking was 3.10 (95% CI, 0.45-21.41). The aORs for more than 30 minutes of daily walking relative to 30 minutes or less of daily walking were found to be 1.54 (95% CI, 0.40-5.95) among men with non-5/5 genotypes and 0.31 (95% CI, 0.12-0.81) for their 5/5 counterparts. The interaction between the genotype and more than 30 minutes of daily walking was 4.92 (95% CI, 0.95-25.64). This study indicated that the ecNOS variable number of tandem repeat polymorphism influences the SUA level in men. Although the interactions were not significant, alcohol intake may be more influential among men with non-5/5 genotypes and walking may be more effective among men with the 5/5 genotype. These findings would be informative for men with high SUA levels.

Adult↗
PubMed2005

Novel stationary-phase-upregulated protein of Porphyromonas gingivalis influences production of superoxide dismutase, thiol peroxidase and thioredoxin.

Porphyromonas gingivalis, an obligately anaerobic bacterium, is implicated as a major pathogen in the development and progression of chronic periodontitis. Although expression of several virulence factors of the bacterium has been found to be affected by environmental stress such as entrance into the stationary growth phase and heat, there is relatively little information on the mechanisms that may operate in the bacterium in response to environmental stress. In this study, a novel protein (UstA) was investigated that was initially identified following two-dimensional gel analysis. Expression of UstA was upregulated in stationary phase or by exposure to atmospheric oxygen. N-terminal sequencing and database analysis with the P. gingivalis genome sequence revealed that the UstA-encoding gene (ustA) was located upstream of a homologue of the usp gene encoding the universal stress protein on the chromosome. The ustA gene appeared to be transcribed in a monocistronic fashion, as revealed by primer extension and Northern blot analysis. To elucidate the role of UstA in the bacterium, chromosomal mutants carrying a disruption of the ustA gene were constructed. The ustA mutant grew slower than the wild-type parent strain in rich medium, resulting in a lower yield in stationary phase. Furthermore, in this mutant, expression levels of the P. gingivalis homologues of superoxide dismutase, thiol peroxidase and thioredoxin were markedly higher than those in the wild-type, especially in stationary phase. The ustA mutant was more resistant to diamide, a thiol-specific oxidant, than the wild-type. In addition, the ustA mutation suppressed hypersensitivities of the oxyR mutant to diamide, metronidazole and mitomycin C. These results suggest that UstA may play a significant role in oxidative stress responses in the bacterium.

Amino Acid Sequence↗