Prenatal exposure to persistent organic pollutants and molar-incisor hypomineralization among 12-year-old children in the French mother-child cohort PELAGIE.

BACKGROUND: Exceptional episodes of exposure to high levels of persistent organic pollutants have already been associated with developmental defects of enamel among children, but knowledge is still scarce concerning the contribution of background levels of environmental contamination. METHODS: Children of the French PELAGIE mother-child cohort were followed from birth, with collection of medical data and cord blood samples that were used to measure polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), and perfluorinated alkyl substances (PFASs). At 12 years of age, molar-incisor hypomineralization (MIH) and other enamel defects (EDs) were recorded for 498 children. Associations were studied using logistic regression models adjusted for potential prenatal confounders. RESULTS: An increasing log-concentration of ß-HCH was associated with a reduced risk of MIH and EDs (OR = 0.55; 95% CI, 0.32-0.95, and OR = 0.65; 95% CI, 0.43-0.98, respectively). Among girls, intermediate levels of p,p'-DDE were associated with a reduced risk of MIH. Among boys, we observed an increased risk of EDs in association with intermediate levels of PCB 138, PCB 153, PCB 187, and an increased risk of MIH with intermediate levels of PFOA and PFOS. CONCLUSIONS: Two OCs were associated with a reduced risk of dental defects, whereas the associations between PCBs and PFASs and EDs or MIH were generally close to null or sex-specific, with an increased risk of dental defects in boys. These results suggest that POPs could impact amelogenesis. Replication of this study is required and the possible underlying mechanisms need to be explored.

Microbiota in Periodontitis: Advances in the Omic Era.

The complexity of the oral microbiome continues to astound researchers even with the advancement of multi-disciplinary strategies being used to study these microorganisms in relation to the human body. There is extensive literature available that explains how oral bacterial communities exist within the biofilm and maintains a balance with the host immune system, but when this balance is tipped disease can occur. The purpose of this review is to highlight the subgingival microbial compositions during health and periodontal disease using next generation sequencing techniques, as well as determining the types of functional activities that partake during these states. The subgingival microbiota is a fluid structure that can adapt accordingly to the environment and the identification of signature biomarkers may aid in the assessment of risk and disease severity in an individual to complement clinical diagnosis in the future.

Porphyromonas gingivalis outside the oral cavity.

Porphyromonas gingivalis, a Gram-negative anaerobic bacillus present in periodontal disease, is considered one of the major pathogens in periodontitis. A literature search for English original studies, case series and review articles published up to December 2019 was performed using the MEDLINE, PubMed and GoogleScholar databases, with the search terms "Porphyromonas gingivalis" AND the potentially associated condition or systemic disease Abstracts and full text articles were used to make a review of published research literature on P. gingivalis outside the oral cavity. The main points of interest of this narrative review were: (i) a potential direct action of the bacterium and not the systemic effects of the inflammatory acute-phase response induced by the periodontitis, (ii) the presence of the bacterium (viable or not) in the organ, or (iii) the presence of its virulence factors. Virulence factors (gingipains, capsule, fimbriae, hemagglutinins, lipopolysaccharide, hemolysin, iron uptake transporters, toxic outer membrane blebs/vesicles, and DNA) associated with P. gingivalis can deregulate certain functions in humans, particularly host immune systems, and cause various local and systemic pathologies. The most recent studies linking P. gingivalis to systemic diseases were discussed, remembering particularly the molecular mechanisms involved in different infections, including cerebral, cardiovascular, pulmonary, bone, digestive and peri-natal infections. Recent involvement of P. gingivalis in neurological diseases has been demonstrated. P. gingivalis modulates cellular homeostasis and increases markers of inflammation. It is also a factor in the oxidative stress involved in beta-amyloid production.

Screening for prevalence and abundance of Capnocytophaga spp by analyzing NGS data: A scoping review.

BACKGROUND: Capnocytophaga spp. are commensal bacteria of the oral cavity and constitute a genus of the core microbiome. OBJECTIVE: This genus is responsible for many local and systemic conditions in both the immunocompetent and immunocompromised patients, but its beneficial or deleterious role in the microbiota has been little explored. DESIGN: Online databases were used to identify papers published from 1999 to 2019 based on next-generation sequencing (NGS) data to study comparative trials. Work using other identification methods, case reports, reviews, and non-comparative clinical trials was excluded. RESULTS AND CONCLUSION: We selected 42 papers from among 668 publications. They showed a link between the abundance of Capnocytophaga spp. in the oral microbiota and various local pathologies (higher for gingivitis and halitosis; lower in active smokers, etc.) or systemic diseases (higher for cancer and carcinomas, IgA nephropathy, etc.). After discussing the limits inherent to the NGS techniques, we present several technical and biological hypotheses to explain the diversity of results observed between studies, as well as the links between the higher or lower abundance of Capnocytophaga spp and the appearance of local or systemic conditions and diseases.

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

OBJECTIVE: To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. DESIGN: We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. RESULTS: Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. CONCLUSIONS: We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.

Role of DNA gyrase and topoisomerase IV mutations in fluoroquinolone resistance of Capnocytophaga spp. clinical isolates and laboratory mutants.

Objectives: Capnocytophaga spp. are often reported to cause bacteraemia and extra-oral infections and are characterized by their significant contribution to resistance to ß-lactam and macrolide-lincosamide-streptogramin antibiotics in the human oral microbiota. The implication of mutations in the quinolone resistance-determining region (QRDR) of DNA gyrase A and B ( gyrA and gyrB ) and topoisomerase IV ( parC and parE ) of fluoroquinolone (FQ)-resistant Capnocytophaga spp., hitherto unknown, was explored in this study. Methods: Two reference strains ( Capnocytophaga gingivalis ATCC 33624 and Capnocytophaga sputigena ATCC 33612) and four Capnocytophaga spp. isolated from clinical samples were studied. Nine in vitro FQ-resistant mutants, derived from two reference strains and one FQ-susceptible clinical isolate, were selected by successive inoculations onto medium containing levofloxacin. MICs of ofloxacin, norfloxacin, ciprofloxacin, levofloxacin and moxifloxacin were determined. The presumed QRDRs of GyrA, GyrB, ParC and ParE from Capnocytophaga spp. were determined by sequence homology to Bacteroides fragilis and Escherichia coli . PCR primers were designed to amplify the presumed QRDR genetic region of Capnocytophaga spp. and sequence analyses were performed using the BLAST program at the National Center for Biotechnology Information. Results and conclusions: gyrA mutations leading to a substitution from amino acid position 80 to 86 were systematically detected in Capnocytophaga spp. with ciprofloxacin MIC >1 mg/L and considered as the primary target of FQs. No mutational alteration in the QRDR of gyrB was detected. Other mutations in parC and parE led to spontaneous amino acid substitutions of DNA topoisomerase IV subunit B with no alteration in FQ susceptibility.

Signature of Microbial Dysbiosis in Periodontitis.

Periodontitis is driven by disproportionate host inflammatory immune responses induced by an imbalance in the composition of oral bacteria; this instigates microbial dysbiosis, along with failed resolution of the chronic destructive inflammation. The objectives of this study were to identify microbial signatures for health and chronic periodontitis at the genus level and to propose a model of dysbiosis, including the calculation of bacterial ratios. Published sequencing data obtained from several different studies (196 subgingival samples from patients with chronic periodontitis and 422 subgingival samples from healthy subjects) were pooled and subjected to a new microbiota analysis using the same Visualization and Analysis of Microbial Population Structures (VAMPS) pipeline, to identify microbiota specific to health and disease. Microbiota were visualized using CoNet and Cytoscape. Dysbiosis ratios, defined as the percentage of genera associated with disease relative to the percentage of genera associated with health, were calculated to distinguish disease from health. Correlations between the proposed dysbiosis ratio and the periodontal pocket depth were tested with a different set of data obtained from a recent study, to confirm the relevance of the ratio as a potential indicator of dysbiosis. Beta diversity showed significant clustering of periodontitis-associated microbiota, at the genus level, according to the clinical status and independent of the methods used. Specific genera (Veillonella, Neisseria, Rothia, Corynebacterium, and Actinomyces) were highly prevalent (>95%) in health, while other genera (Eubacterium, Campylobacter, Treponema, and Tannerella) were associated with chronic periodontitis. The calculation of dysbiosis ratios based on the relative abundance of the genera found in health versus periodontitis was tested. Nonperiodontitis samples were significantly identifiable by low ratios, compared to chronic periodontitis samples. When applied to a subgingival sample set with well-defined clinical data, the method showed a strong correlation between the dysbiosis ratio, as well as a simplified ratio (Porphyromonas, Treponema, and Tannerella to Rothia and Corynebacterium), and pocket depth. Microbial analysis of chronic periodontitis can be correlated with the pocket depth through specific signatures for microbial dysbiosis.IMPORTANCE Defining microbiota typical of oral health or chronic periodontitis is difficult. The evaluation of periodontal disease is currently based on probing of the periodontal pocket. However, the status of pockets "on the mend" or sulci at risk of periodontitis cannot be addressed solely through pocket depth measurements or current microbiological tests available for practitioners. Thus, a more specific microbiological measure of dysbiosis could help in future diagnoses of periodontitis. In this work, data from different studies were pooled, to improve the accuracy of the results. However, analysis of multiple species from different studies intensified the bacterial network and complicated the search for reproducible microbial signatures. Despite the use of different methods in each study, investigation of the microbiota at the genus level showed that some genera were prevalent (up to 95% of the samples) in health or disease, allowing the calculation of bacterial ratios (i.e., dysbiosis ratios). The correlation between the proposed ratios and the periodontal pocket depth was tested, which confirmed the link between dysbiosis ratios and the severity of the disease. The results of this work are promising, but longitudinal studies will be required to improve the ratios and to define the microbial signatures of the disease, which will allow monitoring of periodontal pocket recovery and, conceivably, determination of the potential risk of periodontitis among healthy patients.

Periodontal status and serum biomarker levels in HFE haemochromatosis patients. A case-series study.

AIM: To investigate the association between periodontal status and serum biomarkers in patients with HFE haemochromatosis. MATERIAL AND METHODS: This clinical case series included 84 HFE-C282Y homozygous patients. Periodontal evaluation was performed using clinical attachment level, probing depth, gingival bleeding index, visible plaque index and gingival index. Serum markers of iron metabolism were collected from medical records. The relationship between serum biomarkers of iron burden and the severity of periodontitis was investigated. RESULTS: The study population consisted of 47 men and 37 women, routinely treated in the Unit of Hepatology, University Hospital, Rennes. All patients presented with periodontitis (mild: n = 1, moderate: n = 37 and severe: n = 46). There was a positive association between transferrin saturation >45% and the severity of periodontitis (adjusted odds ratio = 5.49, p = .002). CONCLUSION: Severe periodontitis is associated with the severity of iron burden in patients with HFE-related hereditary haemochromatosis. Dental examination should be included in the initial assessment of all these patients.

Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of human oral Capnocytophaga species.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was evaluated for rapid identification of cfxA PCR positive and negative Capnocytophaga strains. Colonies were grown on blood agar, incubated anaerobically at 37 °C for 48 h, and were then evaluated by MALDI-TOF MS and 16S rRNA gene sequencing. Both methods identified all colonies to the genus level. The MALDI-TOF MS method gave the same result, at the species level, as 16S rRNA gene sequencing for 41/53 Capnocytophaga sp. strains (77.4%), but the limit of this technique was the absence of some species (C. leadbetteri, C. AHN) in the Biotyper-Bruker® database used in this study. Distinction between the cefotaxime resistant and susceptible strains was unsuccessful using the MALDI-TOF MS method. This technique had low discriminatory power to rapidly detect beta-lactamase-producing Capnocytophaga strains in clinical samples. However, the results from a score-oriented dendrogram confirmed MALDI-TOF MS is a rapid, inexpensive, and reliable method for Capnocytophaga species identification. Enrichment of the reference database used (Biotyper®) will improve future results.

Design, synthesis and biological evaluation of potential antibacterial butyrolactones.

Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38µg/mL where they have shown to be stronger bactericidals, by 2-3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9-22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure-activity relationships unveiled that the functional groups at the C4 position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C5 position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C4 position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action.

Multidrug-resistant oral Capnocytophaga gingivalis responsible for an acute exacerbation of chronic obstructive pulmonary disease: Case report and literature review.

INTRODUCTION: Capnocytophaga genus was recently known to highly contribute to the beta-lactam (BL) and macrolide-lincosamide-streptogramin (MLS) resistance gene reservoir in the oral microbiota (BL: blaCSP-1 and blaCfxA; MLS: erm(F) and erm(C)). But fluoroquinolone (FQ) resistance remains uncommon in literature, without available data on resistance mechanisms. CASE REPORT: For the first time, a case of acute exacerbation of chronic obstructive pulmonary disease (COPD) was described in a 78-year-old immunocompetent patient due to a multidrug-resistant Capnocytophaga gingivalis isolate with significant microbiological finding. C.gingivalis acquired resistance to third generation cephalosporins (blaCfxA3 gene), MLS (erm(F) gene), and fluoroquinolones. Genetics of the resistance, unknown as regards fluoroquinolone, was investigated and a substitution in QRDR of GyrA was described (Gly80Asn substitution) for the first time in the Capnocytophaga genus. LITERATURE REVIEW: A comprehensive literature review of Capnocytophaga spp. extra-oral infection was conducted. Including the present report, on 43 cases, 7 isolates were BL-resistant (17%), 4 isolates were MLS-resistant (9.5%) and 4 isolates were FQ-resistant (9.5%). The studied clinical isolate of C.gingivalis was the only one to combine resistance to the three groups of antibiotics BL, MLS and FQ. Four cases of Capnocytophaga lung infection were reported, including three infections involving C. gingivalis (two FQ resistant) and one involving C. sputigena. CONCLUSION: This multidrug-resistant C. gingivalis isolate illustrated the role of oral flora as a reservoir of antibiotic resistance and its contribution to the limitation of effective antibiotics in severe respiratory infections.

cfxA expression in oral clinical Capnocytophaga isolates.

Capnocytophaga spp. are commensal bacteria involved in oral and systemic diseases, with a variable susceptibility to beta-lactams. The cfxA gene expression level was assessed using quantitative RT-PCR, and reasons of the observed misexpression were discussed, as insertion of foreign genetic material, contributing to dissemination and evolution of antibiotic resistance genes.

Strong mutator phenotype drives faster adaptation from growth on glucose to growth on acetate in Salmonella.

The metabolic adaptation of strong mutator strains was studied to better understand the link between the strong mutator phenotype and virulence. Analysis of the growth curves of isogenic strains of Salmonella, which were previously grown in M63 glucose media, revealed that the exponential phase of growth was reached earlier in an M63 acetate medium with strong mutator strains (mutated in mutS or in mutL) than with normomutator strains (P<0.05). Complemented strains confirmed the direct role of the strong mutator phenotype in this faster metabolic adaptation to the assimilation of acetate. In a mixed cell population, proliferation of strong mutators over normomutators was observed when the carbon source was switched from glucose to acetate. These results add to the sparse body of knowledge about strong mutators and highlight the selective advantage conferred by the strong mutator phenotype to adapt to a switch of carbon source in the environment. This work may provide clinically useful information given that there is a high prevalence of strong mutators among pathogenic strains of Salmonella and that acetate is the principal short chain fatty acid of the human terminal ileum and colon where Salmonella infection is localized.

High prevalence of ß-lactam and macrolide resistance genes in human oral Capnocytophaga species.

OBJECTIVES: To determine macrolide-lincosamide-streptogramin (MLS) resistance determinants in the Capnocytophaga genus and to describe the prevalence of ß-lactam resistance genes in human oral Capnocytophaga species. METHODS: Forty-eight Capnocytophaga isolates identified by analysis of 16S rRNA sequences were isolated from subgingival samples from 14 haematology patients (HPs), 11 periodontitis patients (PPs) and 17 healthy volunteers (HVs). MICs of ß-lactam and MLS antibiotics were obtained for all isolates. blaCfxA, blaCSP-1 (encoding a new class A ß-lactamase) and MLS resistance genes [erm(F), erm(B), erm(Q), erm(D), erm(C) and erm(A)] were evaluated using specific PCR and sequencing. RESULTS: In HVs, which had the lowest prevalence of ß-lactamase-producing isolates in comparison with the other groups (16%; P < 0.001), Capnocytophaga ochracea was the prominent species (68%; P < 0.03). In PPs, which had a high prevalence of ß-lactamase-positive isolates (82%; P < 0.001), Capnocytophaga sputigena was more frequently identified (64%; P < 0.03). In HPs, 50% of isolates were ß-lactamase-positive. The more rarely identified species (15%) Capnocytophaga gingivalis, Capnocytophaga granulosa and Capnocytophaga leadbetteri were isolated only from PPs and/or HPs. All ß-lactam-resistant isolates (44%) were PCR-positive for blaCfxA (31%) or blaCSP-1 (12.5%). Interestingly, blaCSP-1 was identified only in a subgroup of the C. sputigena species. Twenty-nine percent of isolates were MLS resistant independently of species identification, ß-lactamase production or patient group. The MLS-resistant isolates carried the erm(F) or erm(C) gene (93% and 7%, respectively), previously unknown in the Capnocytophaga genus. CONCLUSIONS: Our findings illustrate that Capnocytophaga species are important contributors to the ß-lactam and MLS resistance gene reservoir in the oral microbiome.

Biofilms as a mechanism of bacterial resistance.

Inside the biofilm, antimicrobial agents must overcome high cell density, an increased number of resistant mutants, substance delivery, molecular exchanges, such as high levels of beta-lactamases or inducers of efflux pump expression, and specific adaptive cells, so-called persisters. The environment within the biofilm modulates the response to antibiotics, especially when the SOS response or DNA repair systems are involved. Exposure to subinhibitory concentrations of antibiotics can enhance biofilm formation and mutagenesis. Thus, a global response to cell stress seems to be responsible for antibiotic-induced biofilm formation.

[Oral microbiota and liver]. / Microbiote buccal et foie.

The liver has many important biological functions for the body, as it is involved in the storage and distribution of nutrients (carbohydrates to glycogen, lipids to triglycerides), the digestion of fats, the synthesis of blood proteins, and the detoxification of alcohol and drugs. The liver can be affected by various diseases such as viral or drug-induced hepatitis, fibrosis and cirrhosis, in which damaged hepatocytes are progressively replaced by scar tissue.

Title: Microbiote buccal et foie. Abstract: Le foie possède de nombreuses fonctions biologiques importantes pour l'organisme. Il peut être atteint par diverses maladies, telles que les hépatites virales ou médicamenteuses, la fibrose et la cirrhose. Lors de ces affections, les hépatocytes endommagés sont progressivement remplacés par du tissu cicatriciel. Par ailleurs, une altération du microbiote oral peut être à l'origine d'une altération des réponses immunitaires et ainsi contribuer au développement d'une inflammation qui touchera également le foie. En effet, les personnes souffrant d'hémochromatose ou de stéatose hépatique non alcoolique présentent des anomalies importantes du microbiote oral. De même, des concentrations élevées de certaines bactéries colonisant la cavité buccale, telles que Porphyromonas gingivalis, sont associées à des facteurs de risque accrus de stéatose hépatique non alcoolique.

Inactivation of the LysR regulator Cj1000 of Campylobacter jejuni affects host colonization and respiration.

Transcriptional regulation mediates adaptation of pathogens to environmental stimuli and is important for host colonization. The Campylobacter jejuni genome sequence reveals a surprisingly small set of regulators, mostly of unknown function, suggesting an intricate regulatory network. Interestingly, C. jejuni lacks the homologues of ubiquitous regulators involved in stress response found in many other Gram-negative bacteria. Nonetheless, cj1000 is predicted to encode the sole LysR-type regulator in the C. jejuni genome, and thus may be involved in major adaptation pathways. A cj1000 mutant strain was constructed and found to be attenuated in its ability to colonize 1-day-old chicks. Complementation of the cj1000 mutation restored the colonization ability to wild-type levels. The mutant strain was also outcompeted in a competitive colonization assay of the piglet intestine. Oxygraphy was carried out for what is believed to be the first time with the Oroboros Oxygraph-2k on C. jejuni and revealed a role for Cj1000 in controlling O2 consumption. Furthermore, microarray analysis of the cj1000 mutant revealed both direct and indirect regulatory targets, including genes involved in energy metabolism and oxidative stress defences. These results highlight the importance of Cj1000 regulation in host colonization and in major physiological pathways.

Tolerance to intraoral biofilms and their effectiveness in improving mouth dryness and modifying oral microbiota in patients with primary Sjögren's syndrome: "Predelfi study".

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required. Methods: This Predelfi study was a single-center, prospective, comparative, randomized, double-blind, cross-over controlled study with the primary objective of assessing the tolerance to and effectiveness of two adhesive biofilms (containing prebiotics and, sodium alginate, respectively) in patients with pSS and hyposialia (#NCT04206826 in ClinicalTrials.gov). Secondary objectives were to obtain initial data regarding the clinical effectiveness of such biofilms in the improvement of signs and symptoms related to dry mouth and potential changes in the oral microbiota. Ten pSS patients with pSS were included (9 females and 1 male) with a mean age of 58.1 ± 14.0 years. Results and discussion: Tolerance to the prebiotic and sodium alginate biofilms was assessed by the patients (visual analog scale [VAS] score 66.7 and 87.6, respectively) and the practitioner (90 and 100, respectively). The absolute changes in the VAS scores at the start and end of each treatment period highlighted an improvement in mouth dryness for the sodium alginate versus the prebiotic biofilm. The VAS scores for other parameters (mouth burning sensation; taste alteration; chewing; swallowing and speech difficulties) remained globally comparable between the two groups. Unstimulated salivary flow showed no changes regardless of the biofilm used. Regarding the oral microbiota, the sodium alginate biofilm increased the abundance of the Treponema genus, whereas the use of the prebiotic biofilm as the first treatment increased the abundance of the genera Veillonella and Prevotella. Nevertheless, the prebiotic biofilm appeared to stimulate "milder" genera with regard to periodontal infections. Furthermore, pre-treatment with the prebiotic biofilm prevented the emergence of the Treponema genus induced by subsequent treatment with the sodium alginate biofilm, suggesting a potential protective effect.

Complete genome sequence of the strong mutator Salmonella enterica subsp. enterica serotype Heidelberg strain B182.

In bacteria, normal mutation frequencies are mostly around 10(-10) per base pair. However, there exists natural isolates, called "mutators," that exhibit permanent mutation occurrences up to 1,000-fold greater than usual. As mutations play essential roles, particularly in the evolution of antibiotic resistance, bacteria showing elevated mutation rates could have an important responsibility in the emergence of antibiotic resistance, especially in the clinical background. In this announcement, we report the first complete genome sequence of the Salmonella enterica subsp. enterica serotype Heidelberg B182 mutator strain, isolated from bovine feces (France), which consists of a 4,750,465-bp circular chromosome (cB182_4750; GC, 52.2%) and one circular plasmid of 37,581 bp (pB182_37; GC, 42.8%).

Molecular mechanisms of higher MICs of antibiotics and quaternary ammonium compounds for Escherichia coli isolated from bacteraemia.

OBJECTIVES: A previous study identified an association between high MICs of quaternary ammonium compounds (QACs) and antibiotic resistance. The current aim was to investigate the genetic background of this association. METHODS: Of 153 Escherichia coli clinical strains, seven were selected for their low or high MICs of antibiotics and/or QACs. Integron resistance gene contents were identified by sequencing after PCR amplification. The genes encoding the efflux pump AcrA/TolC and its regulatory regions marA, marO, marR, soxS and rob were sequenced. The gene expression of acrA, tolC, marA, marOR, soxS and rob was assessed by quantitative real-time PCR. MICs in the presence and absence of the efflux pump inhibitor phenyl-arginine-ß-naphthylamide (PAßN) were compared. RESULTS: Of the seven strains, five were resistant to amoxicillin, amoxicillin/clavulanic acid and/or co-trimoxazole (trimethoprim/sulfamethoxazole) and/or had high MICs of ciprofloxacin and QACs. Four of the five harboured a class 1 integron (intI1). In three of these four strains, the presence of dfrA/sul1 and qacEΔ1 gene cassettes correlated with resistance to co-trimoxazole and high MICs of QACs. In all of the five strains, overexpression of tolC, marOR and soxS was always associated with higher MICs of antibiotics and/or QACs. PAßN reduced the MICs of ciprofloxacin and QACs, suggesting that extrusion of ciprofloxacin and QACs from bacteria depends on the AcrAB-TolC system. CONCLUSIONS: To our knowledge, this report is the first to describe dual involvement of the AcrAB-TolC system and class 1 integrons in clinical E. coli strains.