Differential response of Porphyromonas gingivalis to varying levels and duration of hydrogen peroxide-induced oxidative stress

McKenzie, Rachelle M E; Johnson, Neal A.; Aruni, Wilson; Dou, Youjun; Masinde, Godfred; Fletcher, Hansel M.

doi:10.1099/mic.0.056416-0

Cited by 30 publications

(58 citation statements)

References 70 publications

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“…The survival of any successful pathogen requires the ability to adapt quickly to changing environments (68). Mounting a rapid stress response would require additional energy at the lowest possible cost to the cell in order to simultaneously maintain minimal cellular functions for survival.…”

Section: Discussionmentioning

confidence: 99%

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

et al. 2016

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Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C 16:1⌬6 ) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls. In this study, we further examined whole-cell protein differences between sapienic acidtreated bacteria and untreated controls, and we utilized open-source functional association and annotation programs to explore potential mechanisms for the antimicrobial activity of sapienic acid. Our analyses indicated that sapienic acid treatment induces a unique stress response in P. gingivalis resulting in differential expression of proteins involved in a variety of metabolic pathways. This network of differentially regulated proteins was enriched in protein-protein interactions (P ‫؍‬ 2.98 ؋ 10 ؊8 ), including six KEGG pathways (P value ranges, 2.30 ؋ 10 ؊5 to 0.05) and four Gene Ontology (GO) molecular functions (P value ranges, 0.02 to 0.04), with multiple suggestive enriched relationships in KEGG pathways and GO molecular functions. Upregulated metabolic pathways suggest increases in energy production, lipid metabolism, iron acquisition and processing, and respiration. Combined with a suggested preferential metabolism of serine, which is necessary for fatty acid biosynthesis, these data support our previous findings that the site of sapienic acid antimicrobial activity is likely at the bacterial membrane. IMPORTANCE P. gingivalis is an important opportunistic pathogen implicated in periodontitis.Affecting nearly 50% of the population, periodontitis is treatable, but the resulting damage is irreversible and eventually progresses to tooth loss. There is a great need for natural products that can be used to treat and/or prevent the overgrowth of periodontal pathogens and increase oral health. Sapienic acid is endogenous to the oral cavity and is a potent antimicrobial agent, suggesting a potential therapeutic or prophylactic use for this fatty acid. This study examines the effects of sapienic acid treatment on P. gingivalis and highlights the membrane as the likely site of antimicrobial activity. Inflammation in the oral cavity ranges from mild and reversible inflammation of the gingiva (gingivitis) to a more chronic inflammation and destruction of tooth-supporting structures (periodontitis). Gingivitis occurs in 50 to 90% of adults worldwide, depending on the widely differing definitions of gingivitis (1). Periodontitis occurs in just over 47% of the U.S. population, with prevalences of 8.7, 30.0, and 8.5% for mild, moderate, and severe periodontitis depending on multiple factors, including oral hygiene, socioeconomic status, educational status, age, and other environmental, genetic, and metabolic risk factors (2). These numbers differ in different populations, and older individuals are at a particular...

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Section: Discussionmentioning

confidence: 99%

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

et al. 2016

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“…Previously, we have assessed the transcriptome response of P. gingivalis to conditions of oxidative challenge depending on the duration or level of exposure (6). This study indicated that P. gingivalis has an adaptive response to oxidative stress that may involve several previously unrecognized genes.…”

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confidence: 99%

“…Several systems, including antioxidant enzymes (reviewed in reference 3), DNA binding proteins (4), the hemin layer (5,6), and enzymatic removal of deleterious products, for example 8-oxoG, caused by reactive oxygen species (ROS) (7), can defend and protect P. gingivalis against oxidative stress-induced damage. The expression of antioxidant-related genes is usually regulated by transcriptional modulators that sense oxidative-stress-generating agents.…”

mentioning

confidence: 99%

Involvement of PG2212 Zinc Finger Protein in the Regulation of Oxidative Stress Resistance in Porphyromonas gingivalis W83

et al. 2014

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dThe adaptation of Porphyromonas gingivalis to H 2 O 2 -induced stress while inducible is modulated by an unknown OxyR-independent mechanism. Previously, we reported that the PG_2212 gene was highly upregulated in P. gingivalis under conditions of prolonged oxidative stress. Because this gene may have regulatory properties, its function in response to H 2 O 2 was further characterized. PG2212, annotated as a hypothetical protein of unknown function, is a 10.3-kDa protein with a cysteine 2-histidine 2 (Cys 2 His 2 ) zinc finger domain. The isogenic mutant P. gingivalis FLL366 (⌬PG_2212) showed increased sensitivity to H 2 O 2 and decreased gingipain activity compared to the parent strain. Transcriptome analysis of P. gingivalis FLL366 revealed that approximately 11% of the genome displayed altered expression (130 downregulated genes and 120 upregulated genes) in response to prolonged H 2 O 2 -induced stress. The majority of the modulated genes were hypothetical or of unknown function, although some are known to participate in oxidative stress resistance. The promoter region of several of the most highly modulated genes contained conserved motifs. In electrophoretic mobility shift assays, the purified rPG2212 protein did not bind its own promoter region but bound a similar region in several of the genes modulated in the PG_2212-deficient mutant. A metabolome analysis revealed that PG2212 can regulate a number of genes coding for proteins involved in metabolic pathways critical for its survival under the conditions of oxidative stress. Collectively, our data suggest that PG2212 is a transcriptional regulator that plays an important role in oxidative stress resistance and virulence regulation in P. gingivalis.

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“…There is a differential response of P. gingivalis to varying concentrations and durations of hydrogen peroxide [123]. As a response to shorter exposure to H2O2-induced oxidative stress, genes involved in DNA replication, recombination and repair were upregulated [123,124]. After a longer exposure, several genes involved in protein folding/repair were upregulated whereas those involved in translation were downregulated.…”

Section: Host Influence On P Gingivalismentioning

confidence: 97%

“…Concurrently, the heme-binding protein IhtB, TonB-dependent receptor P92, Kgp, lipoprotein RagB, endopeptidase PepO, a glutamine cyclotransferase-related protein, fumarate reductases FrdAB, and ribosomal proteins L10, L13 and L25 are significantly decreased. There is a differential response of P. gingivalis to varying concentrations and durations of hydrogen peroxide [123]. As a response to shorter exposure to H2O2-induced oxidative stress, genes involved in DNA replication, recombination and repair were upregulated [123,124].…”

Section: Host Influence On P Gingivalismentioning

confidence: 99%

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

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Differential response of Porphyromonas gingivalis to varying levels and duration of hydrogen peroxide-induced oxidative stress

Cited by 30 publications

References 70 publications

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

Involvement of PG2212 Zinc Finger Protein in the Regulation of Oxidative Stress Resistance in Porphyromonas gingivalis W83

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

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