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Cell Host & Microbe Jan 2019Mosquitoes are hematophagous vectors that can acquire human viruses in their intestinal tract. Here, we define a mosquito gut commensal bacterium that promotes...
Mosquitoes are hematophagous vectors that can acquire human viruses in their intestinal tract. Here, we define a mosquito gut commensal bacterium that promotes permissiveness to arboviruses. Antibiotic depletion of gut bacteria impaired arboviral infection of a lab-adapted Aedes aegypti mosquito strain. Reconstitution of individual cultivable gut bacteria in antibiotic-treated mosquitoes identified Serratia marcescens as a commensal bacterium critical for efficient arboviral acquisition. S. marcescens facilitates arboviral infection through a secreted protein named SmEnhancin, which digests membrane-bound mucins on the mosquito gut epithelia, thereby enhancing viral dissemination. Field Aedes mosquitoes positive for S. marcescens were more permissive to dengue virus infection than those free of S. marcescens. Oral introduction of S. marcescens into field mosquitoes that lack this bacterium rendered these mosquitoes highly susceptible to arboviruses. This study defines a commensal-driven mechanism that contributes to vector competence, and extends our understanding of multipartite interactions among hosts, the gut microbiome, and viruses.
Topics: Aedes; Animals; Anti-Bacterial Agents; Arbovirus Infections; Arboviruses; Bacterial Physiological Phenomena; Culicidae; Dengue Virus; Gastrointestinal Microbiome; Gastrointestinal Tract; Insect Vectors; Microbial Interactions; Mosquito Vectors; Permissiveness; Serratia marcescens
PubMed: 30595552
DOI: 10.1016/j.chom.2018.11.004 -
Cell Chemical Biology May 2022The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is...
The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is known about the factors regulating this process in infected cells. Here we show that HCV is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an iron-dependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2). Genetic depletion and ectopic expression experiments show FADS2 is a key determinant of cellular sensitivity to ferroptosis. Inhibiting FADS2 markedly enhances HCV replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Our results identify FADS2 as a rate-limiting factor in ferroptosis, and suggest the possibility of pharmacologically manipulating the ferroptosis pathway to attenuate viral replication.
Topics: Antiviral Agents; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Ferroptosis; Hepacivirus; Hepatitis C, Chronic; Humans; Iron; Permissiveness; Virus Replication
PubMed: 34520742
DOI: 10.1016/j.chembiol.2021.07.022 -
Genetics Aug 2023A multinucleate syncytium is a common growth form in filamentous fungi. Comprehensive functions of the syncytial state remain unknown, but it likely allows for a wide...
A multinucleate syncytium is a common growth form in filamentous fungi. Comprehensive functions of the syncytial state remain unknown, but it likely allows for a wide range of adaptations to enable filamentous fungi to coordinate growth, reproduction, responses to the environment, and to distribute nuclear and cytoplasmic elements across a colony. Indeed, the underlying mechanistic details of how syncytia regulate cellular and molecular processes spatiotemporally across a colony are largely unexplored. Here, we implemented a strategy to analyze the relative fitness of different nuclear populations in syncytia of Neurospora crassa, including nuclei with loss-of-function mutations in essential genes, based on production of multinucleate asexual spores using flow cytometry of pairings between strains with differentially fluorescently tagged nuclear histones. The distribution of homokaryotic and heterokaryotic asexual spores in pairings was assessed between different auxotrophic and morphological mutants, as well as with strains that were defective in somatic cell fusion or were heterokaryon incompatible. Mutant nuclei were compartmentalized into both homokaryotic and heterokaryotic asexual spores, a type of bet hedging for maintenance and evolution of mutational events, despite disadvantages to the syncytium. However, in pairings between strains that were blocked in somatic cell fusion or were heterokaryon incompatible, we observed a "winner-takes-all" phenotype, where asexual spores originating from paired strains were predominantly one genotype. These data indicate that syncytial fungal cells are permissive and tolerate a wide array of nuclear functionality, but that cells/colonies that are unable to cooperate via syncytia formation actively compete for resources.
Topics: Neurospora crassa; Genes, Fungal; Permissiveness; Phenotype; Giant Cells; Fungal Proteins; Neurospora
PubMed: 37313736
DOI: 10.1093/genetics/iyad112 -
Proceedings of the National Academy of... Dec 2023Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR plasmids are widespread in clinical...
Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR plasmids are widespread in clinical settings, but their distribution is not random, and certain associations between plasmids and bacterial clones are particularly successful. For example, the globally spread carbapenem resistance plasmid pOXA-48 can use a wide range of enterobacterial species as hosts, but it is usually associated with a small number of specific clones. These successful associations represent an important threat for hospitalized patients. However, knowledge remains limited about the factors determining AMR plasmid distribution in clinically relevant bacteria. Here, we combined in vitro and in vivo experimental approaches to analyze pOXA-48-associated AMR levels and conjugation dynamics in a collection of wild-type enterobacterial strains isolated from hospitalized patients. Our results revealed significant variability in these traits across different bacterial hosts, with spp. strains showing higher pOXA-48-mediated AMR and conjugation frequencies than strains. Using experimentally determined parameters, we developed a simple mathematical model to interrogate the contribution of AMR levels and conjugation permissiveness to plasmid distribution in bacterial communities. The simulations revealed that a small subset of clones, combining high AMR levels and conjugation permissiveness, play a critical role in stabilizing the plasmid in different polyclonal microbial communities. These results help to explain the preferential association of plasmid pOXA-48 with clones in clinical settings. More generally, our study reveals that species- and strain-specific variability in plasmid-associated phenotypes shape AMR evolution in clinically relevant bacterial communities.
Topics: Humans; Anti-Bacterial Agents; Permissiveness; Drug Resistance, Bacterial; Plasmids; Klebsiella pneumoniae; Klebsiella; Escherichia coli; Bacteria
PubMed: 38096417
DOI: 10.1073/pnas.2314135120 -
Pediatrics in Review Jan 1987
Review
Topics: Attitude; Child; Child Behavior Disorders; Child Rearing; Child, Preschool; Humans; Infant; Permissiveness
PubMed: 3332352
DOI: 10.1542/pir.8-7-209 -
Pediatric Dentistry 2015This study evaluated the relationship between parenting style, sociodemographic data, caries status, and child's behavior during the first dental visit. (Comparative Study)
Comparative Study
PURPOSE
This study evaluated the relationship between parenting style, sociodemographic data, caries status, and child's behavior during the first dental visit.
METHODS
Parents/legal guardians of new patients aged three to six years presenting to Nationwide Children's Hospital dental clinic for an initial examination/hygiene appointment completed the Parenting Styles and Dimensions Questionnaire (PSDQ) to assess parenting style and a 15-question demographic survey. Blinded and calibrated expanded function dental auxiliaries or dental hygienists (EFDA/DH) performed a prophylaxis and assessed child behavior using the Frankl scale (inter-rater reliability was 92 percent). A blinded and calibrated dentist performed an oral examination.
RESULTS
132 parent/child dyads participated. Children with authoritative parents exhibited more positive behavior (P<.001) and less caries (P<.001) compared to children with authoritarian and permissive parents. Children attending daycare exhibited more positive behavior compared to children who did not (P<.001). Patients with private dental insurance exhibited more positive behavior (P>.04) and less caries (P>.024) compared to children with Medicaid or no dental insurance.
CONCLUSIONS
Authoritative parenting and having private dental insurance were associated with less caries and better behavior during the first dental visit. Attending daycare was associated with better behavior during the first dental visit.
Topics: Black or African American; Authoritarianism; Child; Child Behavior; Child Care; Child Rearing; Child, Preschool; Dental Caries; Educational Status; Female; Humans; Insurance, Dental; Male; Medicaid; Parent-Child Relations; Parenting; Parents; Permissiveness; United States; White People
PubMed: 25685975
DOI: No ID Found -
Bioinformatics (Oxford, England) Jul 2023Wastewater treatment plants (WWTPs) harbor a dense and diverse microbial community. They constantly receive antimicrobial residues and resistant strains, and therefore...
MOTIVATION
Wastewater treatment plants (WWTPs) harbor a dense and diverse microbial community. They constantly receive antimicrobial residues and resistant strains, and therefore provide conditions for horizontal gene transfer (HGT) of antimicrobial resistance (AMR) determinants. This facilitates the transmission of clinically important genes between, e.g. enteric and environmental bacteria, and vice versa. Despite the clinical importance, tools for predicting HGT remain underdeveloped.
RESULTS
In this study, we examined to which extent water cycle microbial community composition, as inferred by partial 16S rRNA gene sequences, can predict plasmid permissiveness, i.e. the ability of cells to receive a plasmid through conjugation, based on data from standardized filter mating assays using fluorescent bio-reporter plasmids. We leveraged a range of machine learning models for predicting the permissiveness for each taxon in the community, representing the range of hosts a plasmid is able to transfer to, for three broad host-range resistance IncP plasmids (pKJK5, pB10, and RP4). Our results indicate that the predicted permissiveness from the best performing model (random forest) showed a moderate-to-strong average correlation of 0.49 for pB10 [95% confidence interval (CI): 0.44-0.55], 0.43 for pKJK5 (0.95% CI: 0.41-0.49), and 0.53 for RP4 (0.95% CI: 0.48-0.57) with the experimental permissiveness in the unseen test dataset. Predictive phylogenetic signals occurred despite the broad host-range nature of these plasmids. Our results provide a framework that contributes to the assessment of the risk of AMR pollution in wastewater systems.
AVAILABILITY AND IMPLEMENTATION
The predictive tool is available as an application at https://github.com/DaneshMoradigaravand/PlasmidPerm.
Topics: Wastewater; RNA, Ribosomal, 16S; Phylogeny; Permissiveness; Plasmids; Microbiota; Gene Transfer, Horizontal
PubMed: 37348862
DOI: 10.1093/bioinformatics/btad400 -
Addictive Behaviors Jul 2021Despite almost 1 in 5 college students being Latinx, research examining risk factors for college alcohol misuse and consequences to inform prevention efforts for Latinx...
BACKGROUND
Despite almost 1 in 5 college students being Latinx, research examining risk factors for college alcohol misuse and consequences to inform prevention efforts for Latinx is limited. The current study attempts to address a health disparity among Latinx college students by examining the effects of parental permissiveness of underage drinking and perceived ethnic discrimination on drinking outcomes.
METHODS
Latinx students from three large and geographically diverse public universities (N = 215; 73% female) completed measures during the fall of their first (T1) and second (T2) years. Analyses used moderated regression with bootstrapping to obtain asymmetrical 95% confidence intervals. Parental permissiveness of underage drinking and perceived ethnic discrimination were assessed as predictors at T1. Drinking outcomes were assessed at T2 as typical weekly drinking, peak blood alcohol content (BAC), and alcohol-related consequences.
RESULTS
T1 permissiveness was significantly positively associated with T2 peak BAC. T1 discrimination significantly moderated the association between T1 permissiveness and T2 peak BAC as well as T2 consequences. The effects of T1 permissiveness on T2 peak BAC and T2 consequences were stronger among Latinx who experienced above-average levels of T1 discrimination.
CONCLUSIONS
Results suggest that among Latinx parental permissiveness of underage drinking and perceived ethnic discrimination are risk factors for peak BAC and alcohol-related consequences. The positive associations between parental permissiveness and peak BAC/consequences were stronger among Latinx students who experienced high levels of ethnic discrimination. Efforts to address these risk factors in future culturally sensitive parent-based interventions for Latinx college students are warranted.
Topics: Alcohol Drinking; Alcohol Drinking in College; Female; Humans; Male; Parenting; Parents; Permissiveness; Risk Factors; Students; Universities
PubMed: 33743494
DOI: 10.1016/j.addbeh.2021.106900 -
Infection and Immunity Feb 2023A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in...
A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile , and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.
Topics: Humans; Animals; Mice; Clostridioides difficile; Butyrates; Permissiveness; Clostridium Infections; Anti-Bacterial Agents; Fatty Acids, Volatile
PubMed: 36692308
DOI: 10.1128/iai.00570-22 -
Social Psychiatry and Psychiatric... Jan 2022Adolescents' perceptions of parental norms may influence their substance use. The relationship between parental norms toward cigarette and alcohol use, and the use of...
PURPOSE
Adolescents' perceptions of parental norms may influence their substance use. The relationship between parental norms toward cigarette and alcohol use, and the use of illicit substances among their adolescent children is not sufficiently investigated. The purpose of this study was to analyze this relationship, including gender differences, using longitudinal data from a large population-based study.
METHODS
The present study analyzed longitudinal data from 3171 12- to 14-year-old students in 7 European countries allocated to the control arm of the European Drug Addiction Prevention trial. The impact of parental permissiveness toward cigarettes and alcohol use reported by the students at baseline on illicit drug use at 6-month follow-up was analyzed through multilevel logistic regression models, stratified by gender. Whether adolescents' own use of cigarette and alcohol mediated the association between parental norms and illicit drug use was tested through mediation models.
RESULTS
Parental permissive norms toward cigarette smoking and alcohol use at baseline predicted adolescents' illicit drug use at follow-up. The association was stronger among boys than among girls and was mediated by adolescents' own cigarette and alcohol use.
CONCLUSION
Perceived parental permissiveness toward the use of legal drugs predicted adolescents' use of illicit drugs, especially among boys. Parents should be made aware of the importance of norm setting, and supported in conveying clear messages of disapproval of all substances.
Topics: Adolescent; Adolescent Behavior; Alcohol Drinking; Child; Cigarette Smoking; Cross-Sectional Studies; Female; Humans; Illicit Drugs; Longitudinal Studies; Male; Parents; Permissiveness; Substance-Related Disorders
PubMed: 34120221
DOI: 10.1007/s00127-021-02118-5