The involvement of CdhR in Porphyromonas gingivalis during nitric oxide stress.

Porphyromonas gingivalis, the causative agent of adult periodontitis, must gain resistance to frequent oxidative and nitric oxide (NO) stress attacks from immune cells in the periodontal pocket to survive. Previously, we found that, in the wild-type and under NO stress, the expression of PG1237 (CdhR), the gene encoding for a putative LuxR transcriptional regulator previously called community development and hemin regulator (CdhR), was upregulated 7.7-fold, and its adjacent gene PG1236 11.9-fold. Isogenic mutants P. gingivalis FLL457 (ΔCdhR::ermF), FLL458 (ΔPG1236::ermF), and FLL459 (ΔPG1236-CdhR::ermF) were made by allelic exchange mutagenesis to determine the involvement of these genes in P. gingivalis W83 NO stress resistance. The mutants were black pigmented and ß hemolytic and their gingipain activities varied with strains. FLL457 and FLL459 mutants were more sensitive to NO compared to the wild type, and complementation restored NO sensitivity to that of the wild type. DNA microarray analysis of FLL457 showed that approximately 2% of the genes were upregulated and over 1% of the genes downregulated under NO stress conditions compared to the wild type. Transcriptome analysis of FLL458 and FLL459 under NO stress showed differences in their modulation patterns. Some similarities were also noticed between all mutants. The PG1236-CdhR gene cluster revealed increased expression under NO stress and may be part of the same transcriptional unit. Recombinant CdhR showed binding activity to the predicted promoter regions of PG1459 and PG0495. Taken together, the data indicate that CdhR may play a role in NO stress resistance and be involved in a regulatory network in P. gingivalis.

Fragmented day-night cycle induces reduced light avoidance, excessive weight gain during early development, and binge-like eating during adulthood in mice.

Fragmented day-night (FDN) cycles are environments in which multiple periods of light and dark alternate across a 24 h period. Exposure to FDN cycles disrupts circadian rhythms, resulting in period lengthening and alterations to mood in mice. A constant light environment, which also induces period lengthening, is linked to mood and metabolic disturbances and disruption to the development of the circadian clock. This study aims to determine how exposure to the FDN cycle impacts development in mice, with the hypothesis that there would be similar and adverse effects as observed in constant light conditions. Our study used CD-1 mice reared under the FDN cycle compared to the commonly used 12 h light: 12 h dark consolidated day-night cycle. During the first week of development, mouse pups reared under the FDN cycle gained bodyweight at a faster rate and did not avoid aberrant light exposure in comparison to 12:12 LD reared mouse pups. Developmental exposure to the FDN cycle lasted two weeks, and then mice were transferred to the 12:12 LD cycle, where after 2 weeks, bodyweight was similar between FDN reared and 12:12 LD reared mice at 1-month and 2-months old. When re-exposed to the FDN cycle during adulthood, FDN reared pups exhibited binge-like eating behaviors and reduced light avoidance. This study shows that the unnatural distribution of light and dark across the 24 h day can cause disruptions during early development that can reappear during adulthood when placed in the same stressful light-dark environment as adults.

What Racism Has to Do with It: Understanding and Reducing Sexually Transmitted Diseases in Youth of Color.

Sexually transmitted diseases (STDs) are high in populations of color compared to Whites. High-risk sexual behaviors are widely viewed as the key contributors to the levels of STDs, especially in adolescents and young adults. This article situates the sexual risk behaviors of Black, Indigenous, and other young people of color within the framework of racism. It begins with an overview of racial inequities in common STDs and shows how racism gives rise to several risk factors for high-risk sexual behaviors. These risk factors for STDs identified in prior research are best understood as adaptations to the challenges and constraints faced by youth in socially disadvantaged environments. Both social adversity and the mental health problems that it triggers can lead to risky sexual behaviors. Drawing on findings from prior research with youth of color, this paper describes the needed interventions that can markedly reduce STDs and their risk factors. It also describes needed research on interventions that could contribute to the knowledge and understanding of the adverse conditions fueled by racism that affect youth of color, their health, and their communities.

The Influence of Black Identity on Wellbeing and Health Behaviors.

BACKGROUND: The aim of this study was to investigate the influence of Black identity on wellbeing and health behaviors. METHODS: Data from the third year (wave) of a longitudinal cohort study (N = 1316) from a large, majority Black, Protestant church of 16,000 members located in Houston, Texas, were used to conduct secondary data analyses. Univariate analyses were used to obtain participants' sociodemographic and health characteristics. ANCOVA and linear regression analyses and Bonferroni adjustments were used to examine the influence of the centrality, public and private regard aspects of Black identity as measured by the Multidimensional Inventory of Black Identity subscales on wellbeing (CES-D scores and self-reported general health) and health behaviors (diet and physical activity levels). RESULTS: Associations were noted between fruit consumption and centrality (F (95,1216) = 2.27) p = .046); soda consumption and private regard (F (5,1214) = 3.04; p = .010); public regard (F (2,1186) = 4.70; p = .009) and physical activity levels; self-reported general health status and private (F (4,1219) = 4.78; p = .001) and public regard (F (4,1211) = 8.53; p < .001). Psychological wellbeing was negatively associated with regard (private (B = -0.030; p < .001) and public regard (B = -0.060; p < .001)). CONCLUSION: Findings suggest that racial identity remain an important factor to consider in addressing health disparities. Racial identity influences mental health, general health, diet and the physical activity levels. Utilizing identity congruent health promotion interventions may positively impact mental, exercise levels, self-reported general health and diet.

Role of the Porphyromonas gingivalis iron-binding protein PG1777 in oxidative stress resistance.

Whole genome sequencing of the response of Porphyromonas gingivalis W83 to hydrogen peroxide revealed an upregulation of several uncharacterized, novel genes. Under conditions of prolonged oxidative stress in P. gingivalis, increased expression of a unique transcriptional unit carrying the grpE, dnaJ and three other hypothetical genes (PG1777, PG1778 and PG1779) was observed. The transcriptional start site of this operon appears to be located 91 bp upstream of the translational start, with a potential -10 region at -3 nt and a -35 region at -39 nt. Isogenic P. gingivalis mutants FLL273 (PG1777 : : ermF-ermAM) and FLL293 (PG1779 : : ermF-ermAM) showed increased sensitivity to and decreased survival after treatment with hydrogen peroxide. P. gingivalis FLL273 showed a fivefold increase in the formation of spontaneous mutants when compared with the parent strain after exposure to hydrogen peroxide. The recombinant PG1777 protein displayed iron-binding properties when incubated with FeSO4 and Fe(NH4)2(SO4).6H2O. The rPG1777 protein protected DNA from degradation when exposed to hydrogen peroxide in the presence of iron. Taken together, the data suggest that the grpE-dnaJ-PG1777-PG1778-PG1779 transcriptional unit may play an important role in oxidative stress resistance in P. gingivalis via its ability to protect against DNA damage.

Antibacterial Activity of Partially Oxidized Ag/Au Nanoparticles against the Oral Pathogen Porphyromonas gingivalis W83.

Advances in nanotechnology provide opportunities for the prevention and treatment of periodontal disease. While physicochemical properties of Ag containing nanoparticles (NPs) are known to influence the magnitude of their toxicity, it is thought that nanosilver can be made less toxic to eukaryotes by passivation of the NPs with a benign metal. Moreover, the addition of other noble metals to silver nanoparticles, in the alloy formulation, is known to alter the silver dissolution behavior. Thus, we synthesized glutathione capped Ag/Au alloy bimetallic nanoparticles (NPs) via the galvanic replacement reaction between maltose coated Ag NPs and chloroauric acid (HAuCl4) in 5% aqueous triblock F127 copolymer solution. We then compared the antibacterial activity of the Ag/Au NPs to pure Ag NPs on Porphyromonas gingivalis W83, a key pathogen in the development of periodontal disease. Only partially oxidized glutathione capped Ag and Ag/Au (Au:Ag≈0.2) NPs inhibited the planktonic growth of P. gingivalis W83. This effect was enhanced in the presence of hydrogen peroxide, which simulates the oxidative stress environment in the periodontal pocket during chronic inflammation.

Life in a Diverse Oral Community - Strategies for Oxidative Stress Survival.

BACKGROUND: While the oral cavity harbors more than 680 bacterial species, the interaction and association of selected bacterial species play a role in periodontal diseases. Bacterial species including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, a consortium previously designated as the "red complex" is now being expanded to include other new emerging pathogens that are significantly associated with periodontal disease. HIGHLIGHT: In addition to novel mechanisms for oxidative resistance of individual species, community dynamics may lead to an overall strategy for survival in the inflammatory environment of the periodontal pocket. Complex systems controlled by response regulators protect against oxidative and nitrosative stress. CONCLUSION: The combination of these multifaceted strategies would provide a comprehensive defense and support system against the repetitive host immune response to promote microbial persistence and disease.

Nitric oxide stress resistance in Porphyromonas gingivalis is mediated by a putative hydroxylamine reductase.

Porphyromonas gingivalis, the causative agent of adult periodontitis, must maintain nitric oxide (NO) homeostasis and surmount nitric oxide stress from host immune responses or other oral bacteria to survive in the periodontal pocket. To determine the involvement of a putative hydroxylamine reductase (PG0893) and a putative nitrite reductase-related protein (PG2213) in P. gingivalis W83 NO stress resistance, genes encoding those proteins were inactivated by allelic exchange mutagenesis. The isogenic mutants P. gingivalis FLL455 (PG0893ermF) and FLL456 (PG2213ermF) were black pigmented and showed growth rates and gingipain and hemolytic activities similar to those of the wild-type strain. P. gingivalis FLL455 was more sensitive to NO than the wild type. Complementation of P. gingivalis FLL455 with the wild-type gene restored the level of NO sensitivity to a level similar to that of the parent strain. P. gingivalis FLL455 and FLL456 showed sensitivity to oxidative stress similar to that of the wild-type strain. DNA microarray analysis showed that PG0893 and PG2213 were upregulated 1.4- and 2-fold, respectively, in cells exposed to NO. In addition, 178 genes were upregulated and 201 genes downregulated more than 2-fold. The majority of these modulated genes were hypothetical or of unknown function. PG1181, predicted to encode a transcriptional regulator, was upregulated 76-fold. Transcriptome in silico analysis of the microarray data showed major metabolomic variations in key pathways. Collectively, these findings indicate that PG0893 and several other genes may play an important role in P. gingivalis NO stress resistance.