Postdoctoral Researcher, HSDM / The Forsyth Institute
What if you could pop a pill and never worry about gum disease and bad breath?
Periodonitits and Gum disease are a major problem in about 40% of the population in the United States. These diseases once established are very hard to get rid of due to a high rate or antibiotic resistance in the disease causing organisms and many other poorly understood mechanisms. Previous research has shown that a subset of oral commensal bacteria (good bacteria that normally live in your oral cavity) when present in high numbers are able to ward off these bad critters or atleast keep them at bay. My research aims to harness this capability of commensal bacteria and use them as probiotics to prevent these diseases and understand the mechanism by which they do that. My data so far has shown several bacteria form healthy oral cavities that are able to prevent a periodontal pathogen that when causes disease can lead to bone and gum loss and is also associated with some types of cancer, rheumatoid arthritis and endocarditis.
The Natural products gordon research conference has leading experts from the field of natural drug discovery attending. The format of the conference allows for open discussion and one on one interaction with these scientists. It will be tremendously helpful to my current as well as future research to get insight and ideas from the leaders in the field.
Abstract: The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.
Pub.: 27 Jul '16, Pinned: 29 Jun '17
Abstract: Dental caries is a costly and prevalent disease characterized by the demineralization of the tooth's enamel. Disease outcome is influenced by host factors, dietary intake, cariogenic bacteria, and other microbes. The cariogenic bacterial species Streptococcus mutans metabolizes sucrose to initiate biofilm formation on the tooth surface and consequently produces lactic acid to degrade the tooth's enamel. Persistence of S. mutans biofilms in the oral cavity can lead to tooth decay. To date, no anticaries therapies that specifically target S. mutans biofilms but do not disturb the overall oral microbiome are available. We screened a library of 2-aminoimidazole antibiofilm compounds with a biofilm dispersion assay and identified a small molecule that specifically targets S. mutans biofilms. At 5 µM, the small molecule annotated 3F1 dispersed 50% of the established S. mutans biofilm but did not disperse biofilms formed by the commensal species Streptococcus sanguinis or Streptococcus gordonii. 3F1 dispersed S. mutans biofilms independently of biofilm-related factors such as antigen I/II and glucosyltransferases. 3F1 treatment effectively prevented dental caries by controlling S. mutans in a rat caries model without perturbing the oral microbiota. Our study demonstrates that selective targeting of S. mutans biofilms by 3F1 was able to effectively reduce dental caries in vivo without affecting the overall oral microbiota shaped by the intake of dietary sugars, suggesting that the pathogenic biofilm-specific treatment is a viable strategy for disease prevention.
Pub.: 03 Jun '17, Pinned: 29 Jun '17
Abstract: Even though the oral microbiome is one of the most complex sites on the body it is an excellent model for narrow-spectrum antimicrobial therapy. Current research indicates disruption of the microbiome leads to a dysbiotic environment allowing for the overgrowth of pathogenic species and the onset of oral diseases. The gram-negative colonizer, Porphyromonas gingivalis has long been considered a key player in the initiation of periodontitis and Streptococcus mutans has been linked to dental caries. With antibiotic research still on the decline, new strategies are greatly needed to combat infectious diseases. By targeting key pathogens, it may be possible to treat oral infections while allowing for the recolonization of the beneficial, healthy flora. In this review, we examine unique strategies to specifically target periodontal pathogens and address what is needed for the success of these approaches in the microbiome era. This article is protected by copyright. All rights reserved.
Pub.: 14 Jun '17, Pinned: 29 Jun '17
Abstract: The scientific literature has demonstrated that probiotics have a broad spectrum of activity, although often the results are contradictory. This study provides a critical overview of the current meta-analyses that have evaluated the efficacy of probiotics in physiological and pathological conditions, such as metabolic disease, antibiotic-associated and Clostridium difficile-associated diarrhea, IBS, constipation, IBD, chemotherapy-associated diarrhea, respiratory tract infection, ventilator-associated pneumonia, NAFLD, liver encephalopathy, periodontitis, depression, vaginosis, urinary tract infections, pancreatitis, incidence of ventilator-associated pneumonia, hospital infection and stay in ICU, mortality of post-trauma patients, necrotising enterocolitis in premature infants. Only for antibiotic- and Clostridium difficile-associated diarrhea, and respiratory tract infections the effects of probiotics are considered "evidence-based". Concerning other fields, meta-analyses lacks to define type and biological effect of probiotic strains, as well as the outcome in a disease state. Therefore, the results presented should be a stimulus for further studies which will provide clinical recommendations.
Pub.: 24 Jun '17, Pinned: 29 Jun '17
Abstract: In this brief review, we discuss our previous research on the relationship between the bacterial composition of salivary microbiota and periodontal disease. Analysis using a terminal restriction fragment length polymorphism method and an international comparison suggest that the predominance of the genera Prevotella and Veillonella in the salivary microbiota is attributable to periodontal disease conditions, and that the predominance of the genus Neisseria indicates healthy periodontal conditions. Furthermore, we recently used next-generation sequencing technology to perform a detailed large-scale analysis of the salivary microbiota. An important finding of that study was that high bacterial richness in the salivary microbiota was significantly associated with poor oral health, as indicated by decayed teeth, periodontitis, and poor oral hygiene. Another important result was that relative abundance of predominant bacteria in saliva was significantly associated with oral health-related conditions. Of the two different cohabiting groups of bacteria found in the salivary microbiota, a greater relative abundance of group I bacteria, which include Prevotella and Veillonella species, was associated with poor oral health, high body mass index, and old age. These findings suggest that the salivary microbiota reflects oral and systemic conditions.
Pub.: 24 Jun '17, Pinned: 29 Jun '17
Abstract: Selection for probiotic candidates by in vivo experimental trials is time and labor consuming; more informed strategy is needed to select successful probiotic candidates. The aim of the study was to elucidate the microbial taxa transmitted from maize seeds to seedlings during the germination process of maize and their probiotic effects. The bacterial and fungal taxa in kernel germs and sprouts were analyzed by Illumina-based sequencing. The sprouts contained more diverse fungi than those in germs. The bacterial species (OTUs) declined with the germination from germs to the sprouts. However, the endophytic fungal diversity increased during the germination process. Seed-borne dominant bacterial genera Bacillus, Halomonas, and Shewanella and dominant fungal genera Aspergillus were also detected in sprouts. The spore-forming bacteria BS3 isolated directly from sprouts could promote growth of maize seedling and resistance to F. verticillioides under F. verticillioides-infested soils. The results suggested that maize contained core bacterial and fungal taxa during the development from seeds to sprouts, and the core endophytes showed more intimate correlation with host plants than did other microbial taxa. Illumina-based sequence analysis is feasible to guide probiotic candidate selection and isolation.
Pub.: 24 Jun '17, Pinned: 29 Jun '17