scholarly journals Commensal Oral Rothia mucilaginosa Produces Enterobactin, a Metal-Chelating Siderophore

mSystems ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Carla C. Uranga ◽  
Pablo Arroyo ◽  
Brendan M. Duggan ◽  
William H. Gerwick ◽  
Anna Edlund

ABSTRACT Next-generation sequencing studies of saliva and dental plaque from subjects in both healthy and diseased states have identified bacteria belonging to the Rothia genus as ubiquitous members of the oral microbiota. To gain a deeper understanding of molecular mechanisms underlying the chemical ecology of this unexplored group, we applied a genome mining approach that targets functionally important biosynthetic gene clusters (BGCs). All 45 genomes that were mined, representing Rothia mucilaginosa, Rothia dentocariosa, and Rothia aeria, harbored a catechol-siderophore-like BGC. To explore siderophore production further, we grew the previously characterized R. mucilaginosa ATCC 25296 in liquid cultures, amended with glycerol, which led to the identification of the archetype siderophore enterobactin by using tandem liquid chromatography-mass spectrometry (LC-MS/MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy. Normally attributed to pathogenic gut bacteria, R. mucilaginosa is the first commensal oral bacterium found to produce enterobactin. Cocultivation studies including R. mucilaginosa or purified enterobactin revealed that enterobactin reduced growth of certain strains of cariogenic Streptococcus mutans and pathogenic strains of Staphylococcus aureus. Commensal oral bacteria were either unaffected, reduced in growth, or induced to grow adjacent to enterobactin-producing R. mucilaginosa or the pure compound. Taken together with Rothia’s known capacity to ferment a variety of carbohydrates and amino acids, our findings of enterobactin production add an additional level of explanation to R. mucilaginosa’s prevalence in the oral cavity. Enterobactin is the strongest Fe(III) binding siderophore known, and its role in oral health requires further investigation. IMPORTANCE The communication language of the human oral microbiota is vastly underexplored. However, a few studies have shown that specialized small molecules encoded by BGCs have critical roles such as in colonization resistance against pathogens and quorum sensing. Here, by using a genome mining approach in combination with compound screening of growth cultures, we identified that the commensal oral community member R. mucilaginosa harbors a catecholate-siderophore BGC, which is responsible for the biosynthesis of enterobactin. The iron-scavenging role of enterobactin is known to have positive effects on the host’s iron pool and negative effects on host immune function; however, its role in oral health remains unexplored. R. mucilaginosa was previously identified as an abundant community member in cystic fibrosis, where bacterial iron cycling plays a major role in virulence development. With respect to iron’s broad biological importance, iron-chelating enterobactin may explain R. mucilaginosa’s colonization success in both health and disease.

2020 ◽  
Author(s):  
Carla Uranga ◽  
Pablo Arroyo ◽  
Brendan M. Duggan ◽  
William H. Gerwick ◽  
Anna Edlund

AbstractNext-generation sequencing studies of saliva and dental plaque from subjects in both healthy and diseased states have identified bacteria belonging to the Rothia genus as ubiquitous members of the oral microbiota. To gain a deeper understanding of molecular mechanisms underlying the chemical ecology of this unexplored group, we applied a genome mining approach that targets functionally important biosynthetic gene clusters (BGCs). All 45 genomes that were mined, representing Rothia mucilaginosa, R. dentocariosa and R. aeria, harbored a catechol-siderophore-like BGC. To explore siderophore production further we grew the previously characterized R. mucilaginosa ATCC 25296 in liquid cultures, amended with glycerol, which led to the identification of the archetype siderophore enterobactin by using tandem Liquid Chromatography Mass Spectrometry (LC/MS/MS), High Performance Liquid Chromatography (HPLC), and Nuclear Magnetic Resonance (NMR) spectroscopy. Normally attributed to pathogenic gut bacteria, R. mucilaginosa is the first commensal oral bacterium found to produce enterobactin. Co-cultivation studies including R. mucilaginosa or purified enterobactin revealed that enterobactin reduced growth of certain strains of cariogenic Streptococcus mutans and pathogenic strains of Staphylococcus aureus. Commensal oral bacteria were either unaffected by, reduced in growth, or induced to grow adjacent to enterobactin producing R. mucilaginosa or the pure compound. Taken together with Rothia’s known capacity to ferment a variety of carbohydrates and amino acids, our findings of enterobactin production adds an additional level of explanation to R. mucilaginosa’s colonization success of the oral cavity. Enterobactin is the strongest Fe(III)-binding siderophore known, and its role in oral health requires further investigation.ImportanceThe communication language of the human oral microbiota is vastly underexplored. However, a few studies have shown that specialized small molecules encoded by BGCs have critical roles such as in colonization resistance against pathogens and quorum sensing. Here, by using a genome mining approach in combination with compound screening of growth cultures, we identified that the commensal oral community member mucilaginosa harbors a catecholate-siderophore BGC, which is responsible for the biosynthesis of enterobactin. The iron-scavenging role of enterobactin is known to have positive effects on the host’s iron pool and negative effects on host immune function, however its role in oral health remains unexplored. R. mucilaginosa was previously identified as an abundant community member in cystic fibrosis, where bacterial iron cycling plays a major role in virulence development. With respect to iron’s broad biological importance, iron-chelating enterobactin may explain R. mucilaginosa’s colonization success in both health and disease.


2011 ◽  
Vol 77 (17) ◽  
pp. 6117-6124 ◽  
Author(s):  
Martin F. Kreutzer ◽  
Hirokazu Kage ◽  
Peter Gebhardt ◽  
Barbara Wackler ◽  
Hans P. Saluz ◽  
...  

ABSTRACTA genome mining study in the plant pathogenic bacteriumRalstonia solanacearumGMI1000 unveiled a polyketide synthase/nonribosomal peptide synthetase gene cluster putatively involved in siderophore biosynthesis. Insertional mutagenesis confirmed the respective locus to be operational under iron-deficient conditions and spurred the isolation of the associated natural product. Bioinformatic analyses of the gene cluster facilitated the structural characterization of this compound, which was subsequently identified as the antimycoplasma agent micacocidin. The metal-chelating properties of micacocidin were evaluated in competition experiments, and the cellular uptake of gallium-micacocidin complexes was demonstrated inR. solanacearumGMI1000, indicating a possible siderophore role. Comparative genomics revealed a conservation of the micacocidin gene cluster in defined, but globally dispersed phylotypes ofR. solanacearum.


2019 ◽  
Vol 85 (21) ◽  
Author(s):  
K. Lee ◽  
A. R. Walker ◽  
B. Chakraborty ◽  
J. R. Kaspar ◽  
M. M. Nascimento ◽  
...  

ABSTRACT Health-associated biofilms in the oral cavity are composed of a diverse group of microbial species that can foster an environment that is less favorable for the outgrowth of dental caries pathogens, like Streptococcus mutans. A novel oral bacterium, designated Streptococcus A12, was previously isolated from supragingival dental plaque of a caries-free individual and was shown to interfere potently with the growth and virulence properties of S. mutans. In this study, we applied functional genomics to begin to identify molecular mechanisms used by A12 to antagonize, and to resist the antagonistic factors of, S. mutans. Using bioinformatics, genes that could encode factors that enhance the ability of A12 to compete with S. mutans were identified. Selected genes, designated potential competitive factors (pcf), were deleted. Certain mutant derivatives showed a reduced capacity to compete with S. mutans compared to that of the parental strain. The A12 pcfO mutant lost the ability to inhibit comX-inducing peptide (XIP) signaling by S. mutans, while mutants with changes in the pcfFEG locus were impaired in sensing of, and were more sensitive to, the lantibiotic nisin. Loss of PcfV, annotated as a colicin V biosynthetic protein, resulted in diminished antagonism of S. mutans. Collectively, the data provide new insights into the complexities and variety of factors that affect biofilm ecology and virulence. Continued exploration of the genomic and physiological factors that distinguish commensals from truly beneficial members of the oral microbiota will lead to a better understanding of the microbiome and new approaches to promote oral health. IMPORTANCE Advances in defining the composition of health-associated biofilms have highlighted the important role of beneficial species in maintaining health. Comparatively little, however, has been done to address the genomic and physiological bases underlying the probiotic mechanisms of beneficial commensals. In this study, we explored the ability of a novel oral bacterial isolate, Streptococcus A12, to compete with the dental pathogen Streptococcus mutans using various gene products with diverse functions. A12 displayed enhanced competitiveness by (i) disrupting intercellular communication pathways of S. mutans, (ii) sensing and resisting antimicrobial peptides, and (iii) producing factors involved in the production of a putative antimicrobial compound. Research on the probiotic mechanisms employed by Streptococcus A12 is providing essential insights into how beneficial bacteria may help maintain oral health, which will aid in the development of biomarkers and therapeutics that can improve the practice of clinical dentistry.


mSphere ◽  
2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Kaitlin J. Flynn ◽  
Nielson T. Baxter ◽  
Patrick D. Schloss

ABSTRACT The oral periodontopathic bacterium Fusobacterium nucleatum has been repeatedly associated with colorectal tumors. Molecular analysis has identified specific virulence factors that promote tumorigenesis in the colon. However, other oral community members, such as members of the Porphyromonas spp., are also found with F. nucleatum on colonic tumors, and thus, narrow studies of individual pathogens do not take community-wide virulence properties into account. A broader view of oral bacterial physiology and pathogenesis identifies two factors that could promote colonization and persistence of oral bacterial communities in the colon. The polymicrobial nature of oral biofilms and the asaccharolytic metabolism of many of these species make them well suited to life in the microenvironment of colonic lesions. Consideration of these two factors offers a novel perspective on the role of oral microbiota in the initiation, development, and treatment of colorectal cancer.


2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Enzo A. Palombo

Oral diseases are major health problems with dental caries and periodontal diseases among the most important preventable global infectious diseases. Oral health influences the general quality of life and poor oral health is linked to chronic conditions and systemic diseases. The association between oral diseases and the oral microbiota is well established. Of the more than 750 species of bacteria that inhabit the oral cavity, a number are implicated in oral diseases. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria (mutans streptococci, lactobacilli and actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria (Porphyromonas gingivalis,Actinobacillus,PrevotellaandFusobacterium). Given the incidence of oral disease, increased resistance by bacteria to antibiotics, adverse affects of some antibacterial agents currently used in dentistry and financial considerations in developing countries, there is a need for alternative prevention and treatment options that are safe, effective and economical. While several agents are commercially available, these chemicals can alter oral microbiota and have undesirable side-effects such as vomiting, diarrhea and tooth staining. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, plant extracts or phytochemicals that inhibit the growth of oral pathogens, reduce the development of biofilms and dental plaque, influence the adhesion of bacteria to surfaces and reduce the symptoms of oral diseases will be discussed further. Clinical studies that have investigated the safety and efficacy of such plant-derived medicines will also be described.


2020 ◽  
Vol 86 (16) ◽  
Author(s):  
Stanley O. Onyango ◽  
Nele De Clercq ◽  
Koen Beerens ◽  
John Van Camp ◽  
Tom Desmet ◽  
...  

ABSTRACT This study compares the metabolic properties of kojibiose, trehalose, sucrose, and xylitol upon incubation with representative oral bacteria as monocultures or synthetic communities or with human salivary bacteria in a defined medium. Compared to sucrose and trehalose, kojibiose resisted metabolism during a 48-h incubation with monocultures, except for Actinomyces viscosus. Incubations with Lactobacillus-based communities, as well as salivary bacteria, displayed kojibiose metabolism, yet to a lesser extent than sucrose and trehalose. Concurring with our in vitro findings, screening for carbohydrate-active enzymes revealed that only Lactobacillus spp. and A. viscosus possess enzymes from glycohydrolase (GH) families GH65 and GH15, respectively, which are associated with kojibiose metabolism. Donor-dependent differences in salivary microbiome composition were noted, and differences in pH drop during incubation indicated different rates of sugar metabolism. However, functional analysis indicated that lactate, acetate, and formate evenly dominated the metabolic profile for all sugars except for xylitol. 16S rRNA gene sequencing analysis and α-diversity markers revealed that a significant shift of the microbiome community by sugars was more pronounced in sucrose and trehalose than in kojibiose and xylitol. In Streptococcus spp., a taxon linked to cariogenesis dominated in sucrose (mean ± standard deviation, 91.8 ± 6.4%) and trehalose (55.9 ± 38.6%), representing a high diversity loss. In contrast, Streptococcus (5.1 ± 3.7%) was less abundant in kojibiose, which instead was dominated by Veillonella (26.8 ± 19.6%), while for xylitol, Neisseria (29.4 ± 19.1%) was most abundant. Overall, kojibiose and xylitol incubations stimulated cariogenic species less yet closely maintained an abundance of key phyla and genera of the salivary microbiome, suggesting that kojibiose has low cariogenic properties. IMPORTANCE This study provides a detailed scientific insight on the metabolism of a rare disaccharide, kojibiose, whose mass production has recently been made possible. While the resistance of kojibiose was established with monocultures, delayed utilization of kojibiose was observed with communities containing lactobacilli and A. viscosus as well as with complex communities of bacteria from human saliva. Kojibiose is, therefore, less metabolizable than sucrose and trehalose. Moreover, although conventional sugars cause distinct shifts in salivary microbial communities, our study has revealed that kojibiose is able to closely maintain the salivary microbiome composition, suggesting its low cariogenic properties. This study furthermore underscores the importance and relevance of microbial culture and ex vivo mixed cultures to study cariogenicity and substrate utilization; this is in sharp contrast with tests that solely rely on monocultures such as Streptococcus mutans, which clearly fail to capture complex interactions between oral microbiota.


2019 ◽  
Vol 8 (28) ◽  
Author(s):  
Walaa E. Hussein ◽  
Lingzi Xiaoli ◽  
Ahmed E. Yousef

Enterococcus durans OSY-EGY was isolated recently from cheese. The strain produces potent antimicrobial agents. Here, we present the draft genome sequence of the strain, with a genome size of 3,230,625 bp and an average G+C content of 37.69%. Draft genome mining identified several biosynthetic gene clusters encoding multiple antimicrobial peptides.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Kjersti Berge Evensen ◽  
Vibeke Hervik Bull ◽  
Linda Ness

Purpose Prisoners have poorer oral health than the general population. Good oral health is essential for both social and physical well-being. For prisoners, poor oral health is also related to drug use after release, whereas good oral health is related to successful reintegration into society. The purpose of this study was twofold: to examine the effect of an intervention based on motivational interviewing (MI) on prisoners’ oral health-related behavior and to assess if the intervention is a good fit for this population. Design/methodology/approach In total, 16 prisoners in a Norwegian prison were offered a brief MI-based intervention focusing on changing their oral health-related behavior. An oral examination was also performed and the prisoners received a small package containing oral hygiene aids. Two weeks later, a second oral examination and a semi-structured interview were conducted to explore the effect of the intervention and examine the prisoners’ responses to the intervention. Qualitative data analyzes were guided by thematic analysis. Findings The findings indicate that the intervention had positive effects on both the prisoners’ motivation to use oral health-related behavior and their performance of oral health-related behavior. The findings also indicate that the intervention was well adapted to the target population. Originality/value This is one of the first studies that explore the effect of an intervention in improving prisoners’ oral health and bridges a knowledge gap in the literature. The findings may increase the understanding of how dental services should be organized and offered to provide dental health care to this vulnerable group.


2021 ◽  
Author(s):  
Jason Nomburg ◽  
Susan Bullman ◽  
Dariush Nasrollahzadeh ◽  
Eric A. Collisson ◽  
Behnoush Abedi-Ardekani ◽  
...  

ABSTRACTThe incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.


2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Sheeba Thomas ◽  
David F. Lappin ◽  
Christopher J. Nile ◽  
Julie Spears ◽  
David Bennett ◽  
...  

Introduction. Feline odontoclastic resorptive lesion (FORL) is one of the most common and painful oral diseases of the cat. It is characterised by tooth resorption due to destructive activity of odontoclasts. FORL can result in tooth loss. While the aetiology of FORL is not clearly understood, it is thought to be multifactorial and bacteria are likely to play a major role. Hypothesis. Dysbiosis of the normal feline oral microbiota leads to an alteration in commensal bacteria populations, which results in the development of FORL. Aim. The purpose of the current study was to determine the composition of the microbiomes associated with feline oral health and FORL. Methodology. Supragingival plaque was collected from 25 cats with a healthy oral cavity and 40 cats with FORL. DNA was extracted from each sample, the V4 region of the 16S rRNA gene amplified by polymerase chain reaction and amplicons sequenced. Diversity and species richness analyses were performed, principal component analysis was used to explore differences between the oral microbiomes of healthy cats and those with FORL, and linear discriminant analysis effect size was used to assess differences between the groups. Results. The six most abundant bacterial genera identified were Bergeyella , Capnocytophaga, Lampropedia, Morexella, Porphyromonas and Treponema . Two-step cluster analysis of the data identified two FORL sub-groups (FORL-1, FORL-2). The FORL-2 sub-group was very similar to the healthy group, whilst the FORL-1 sub-group was clearly different from both the FORL-2 sub-group and the healthy groups. In this analysis, Capnocytophaga (P <0.001) and Lampropedia (P <0.01) were found at significantly lower levels and Porphyromonas at a slightly higher level in the FORL-1 sub-group compared to the healthy and FORL-2 sub-groups. Microbial diversity was found to be less in the FORL-1 sub-group than in the healthy group. Lampropedia sp., a phosphate-accumulating oral commensal species, was significantly lower in the FORL-1 sub-group. Conclusion. The oral microbiota associated with the FORL-1 sub-group is distinct from that found in the healthy group and FORL-2 sub-group. Lampropedia species may influence the local calcium-phosphate ratio, which could be a factor in tooth and bone resorption observed in FORL.


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