Structure-activity relationships of synthetic analogs of jasmonic acid and coronatine on induction of benzo[c]phenanthridine alkaloid accumulation in Eschscholzia californica cell cultures

A facile test system based on the accumulation of benzo[c]phenanthridine alkaloids in Eschscholzia californica cell suspension culture (an indicator of defense gene activation) has been used to analyze a series of synthetic compounds for elicitor-like activity. Of the 200 jasmonic acid and coronatine analogs tested with this system, representative results obtained with 49 of them are presented here. The following can be summarized concerning structure-actvity relationships: there is a large degree of plasticity allowed at the C-3 of jasmonic acid in the activation of defense genes. The carbonyl moiety is not strictly required, but exocyclic double bond character appears necessary. The pentenyl side chain at C-2 cannot tolerate bulky groups at the terminal carbon and still be biologically active. Substitutions to the C-1' position are tolerated if they can potentially undergo beta-oxidation. Either an alkanoic acid or methyl ester is required at c-l, or a side chain that can be shortened by beta-oxidation or by peptidase hydrolysis. Coronatine and various derivatives thereof are not as effective as jasmonic acid, and derivatives in inducing benzo[c]phenanthridine alkaloid accumulation. Jasmonic acid rather than the octadecanoic precursors is therefore considered to be a likely signal transducer of defense gene activation in planta

Studies on fusobacteria associated with periodontal diseases

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.The physiological and metabolic characteristics of representative isolates of the various subspecies of Fusobacterium nucleatum were investigated by growing them in continuous culture in chemically-defined media. Behaving almost identically, these organisms were found to obtain energy from the fermentation of simple carbohydrates such as glucose or fructose or from the fermentation of certain amino acids, free or in the form of small peptides. The latter can be attacked by aminopeptidase activity which was shown to be essential for the growth of the organism in an environment lacking fermentable carbohydrate and free amino acids but replete with small peptides. This metabolic versatility may explain the presence of F nucleatum in both supra- and sub-gingival dental plaque and why it is often found together with organisms such as Porphyromonas gingivalis which display powerful endopeptidase activities. Using the technique of allozyme electrophoresis, the current subspeciation of F. nucleatum was shown to be of doubtful validity and evidence, based upon physiological and metabolic properties, for differences in pathogenicity between isolates was not detected. While this organism is a member of various bacterial consortia associated with periodontal diseases, its contribution to the disease process remains unclear.AH Roger

Whole-Genome Sequences and Classification of

In collaboration with the CDC’s Streptococcus Laboratory, we report here the whole-genome sequences of seven Streptococcus agalactiae bacteria isolated from laboratory-reared Long-Evans rats. Four of the S. agalactiae isolates were associated with morbidity accompanied by endocarditis, metritis, and fatal septicemia, providing an opportunity for comparative genomic analysis of this opportunistic pathogen.United States. National Institutes of Health (T32-OD010978)United States. National Institutes of Health (P30-ES002109

Diagnostic potential of chromogenic substrates for rapid detection of bacterial enzymatic activity in health and disease associated periodontal plaques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65525/1/j.1600-0765.1984.tb01327.x.pd

Benzoyl-arginine naphthylamide (BANA) hydrolysis by Treponema denticola and/or Bacteroides gingivalis in periodontal plaques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73624/1/j.1399-302X.1990.tb00425.x.pd

Alterations in common marmoset gut microbiome associated with duodenal strictures

Chronic gastrointestinal (GI) diseases are the most common diseases in captive common marmosets (Callithrix jacchus). Despite standardized housing, diet and husbandry, a recently described gastrointestinal syndrome characterized by duodenal ulcers and strictures was observed in a subset of marmosets sourced from the New England Primate Research Center. As changes in the gut microbiome have been associated with GI diseases, the gut microbiome of 52 healthy, non-stricture marmosets (153 samples) were compared to the gut microbiome of 21 captive marmosets diagnosed with a duodenal ulcer/stricture (57 samples). No significant changes were observed using alpha diversity metrics, and while the community structure was significantly different when comparing beta diversity between healthy and stricture cases, the results were inconclusive due to differences observed in the dispersion of both datasets. Differences in the abundance of individual taxa using ANCOM, as stricture-associated dysbiosis was characterized by Anaerobiospirillum loss and Clostridium perfringens increases. To identify microbial and serum biomarkers that could help classify stricture cases, we developed models using machine learning algorithms (random forest, classification and regression trees, support vector machines and k-nearest neighbors) to classify microbiome, serum chemistry or complete blood count (CBC) data. Random forest (RF) models were the most accurate models and correctly classified strictures using either 9 ASVs (amplicon sequence variants), 4 serum chemistry tests or 6 CBC tests. Based on the RF model and ANCOM results, C. perfringens was identified as a potential causative agent associated with the development of strictures. Clostridium perfringens was also isolated by microbiological culture in 4 of 9 duodenum samples from marmosets with histologically confirmed strictures. Due to the enrichment of C. perfringens in situ, we analyzed frozen duodenal tissues using both 16S microbiome profiling and RNAseq. Microbiome analysis of the duodenal tissues of 29 marmosets from the MIT colony confirmed an increased abundance of Clostridium in stricture cases. Comparison of the duodenal gene expression from stricture and non-stricture marmosets found enrichment of genes associated with intestinal absorption, and lipid metabolism, localization, and transport in stricture cases. Using machine learning, we identified increased abundance of C. perfringens, as a potential causative agent of GI disease and intestinal strictures in marmosets.National Institutes of Health/[T32 OD010978]/NIH/Estados UnidosNational Institutes of Health/[P30-ES002109]/NIH/Estados UnidosUniversidad de Costa Rica/[803-C1-163]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: Comparison of two dosage regimens

: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three of four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial.: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assgined (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomysin orally four times daily for an average of 10 days.: No significant differences in measurable responses to the two regimens wre noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients.: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28100/1/0000547.pd

Vaccines against periodontitis: a forward-looking review

Periodontal disease, as a polymicrobial disease, is globally endemic as well as being a global epidemic. It is the leading cause for tooth loss in the adult population and has been positively related to life-threatening systemic diseases such as atherosclerosis and diabetes. As a result, it is clear that more sophisticated therapeutic modalities need to be developed, which may include vaccines. Up to now, however, no periodontal vaccine trial has been successful in satisfying all the requirements; to prevent the colonization of a multiple pathogenic biofilm in the subgingival area, to elicit a high level of effector molecules such as immunoglobulin sufficient to opsonize and phagocytose the invading organisms, to suppress the induced alveolar bone loss, or to stimulate helper T-cell polarization that exerts cytokine functions optimal for protection against bacteria and tissue destruction. This article reviews all the vaccine trials so as to construct a more sophisticated strategy which may be relevant in the future. As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, CD4+, CD25+, FoxP3+) have also been introduced. Targeting not only a single pathogen, but polymicrobial organisms, and targeting not only periodontal disease, but also periodontal disease-triggered systemic disease could be a feasible goal

Direct Bacterial Killing In Vitro by Recombinant Nod2 Is Compromised by Crohn's Disease-Associated Mutations

Background: A homeostatic relationship with the intestinal microflora is increasingly appreciated as essential for human health and wellbeing. Mutations in the leucine-rich repeat (LRR) domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn’s disease. We investigated the molecular mechanisms underlying disruption of intestinal symbiosis in patients carrying Nod2 mutations. Methodology/Principal Findings: In this study, using purified recombinant LRR domains, we demonstrate that Nod2 is a direct antimicrobial agent and this activity is generally deficient in proteins carrying Crohn’s-associated mutations. Wildtype, but not Crohn’s-associated, Nod2 LRR domains directly interacted with bacteria in vitro, altered their metabolism and disrupted the integrity of the plasma membrane. Antibiotic activity was also expressed by the LRR domains of Nod1 and other pattern recognition receptors suggesting that the LRR domain is a conserved anti-microbial motif supporting innate cellular immunity. Conclusions/Significance: The lack of anti-bacterial activity demonstrated with Crohn’s-associated Nod2 mutations in vitro, supports the hypothesis that a deficiency in direct bacterial killing contributes to the association of Nod2 polymorphism