Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. In this prospective cohort study, we investigate the nasopharynx resistome development in preterm infants, assess early antibiotic impact on its trajectory, and explore its association with clinical covariates using shotgun metagenomics.
View Article and Find Full Text PDFAntifungal agents are widely used to specifically eliminate infections by fungal pathogens. However, the specificity of antifungal agents has been challenged by a few studies demonstrating antibacterial inhibitory effects against and species. Here, we evaluated for the first time the potential effect of fluconazole, the most clinically used antifungal agent, on a human oral microbiota biofilm model.
View Article and Find Full Text PDFEmerging evidence suggests differential effects of therapeutic antibiotics on infant T cell responses to pathogens. In this study, we explored the impact of the treatment of mouse infants with amoxicillin and the human milk-derived antimicrobial HAMLET (human alpha-lactalbumin made lethal to tumor cells) on T cell responses to . Lung cells and splenocytes were isolated from the infant mice subjected to intranasal administration of amoxicillin, HAMLET, or a combination of HAMLET and amoxicillin, and cultured with to measure T cell responses.
View Article and Find Full Text PDFIntroduction: Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirate samples from premature infants, focusing on host DNA depletion and microbiome and resistome characterization.
View Article and Find Full Text PDFThe collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome.
View Article and Find Full Text PDFBackground: The antimicrobial resistance (AMR) crisis is a major global threat and one of its biggest drivers is the overuse of antibiotics in humans. Dentists are responsible for 5-10% antibiotic prescriptions worldwide and recent data suggest that knowledge and prescribing practices need improvement.
Methods: A cross-sectional web-survey was sent to dental students from six universities in Norway, Canada, and Brazil.
Selective markers employed in classical mutagenesis methods using natural genetic transformation can affect gene expression, risk phenotypic effects, and accumulate as unwanted genes during successive mutagenesis cycles. In this chapter, we present a protocol for markerless genome editing in Streptococcus mutans and Streptococcus pneumoniae achieved with an efficient method for natural transformation. High yields of transformants are obtained by combining the unimodal state of competence developed after treatment of S.
View Article and Find Full Text PDFAntibiotics seize an effect on bacterial composition and diversity and have been demonstrated to induce disruptions on gut microbiomes. This may have implications for human health and wellbeing, and an increasing number of studies suggest a link between the gut microbiome and several diseases. Hence, reducing antibiotic treatments may be beneficial for human health status.
View Article and Find Full Text PDFOral biofilms can be a major health problem causing infections and chronic inflammation of mucosal tissue. While much effort is put in the investigation of bacteria in biofilms, the role of fungi is often neglected, despite Candida albicans playing a key role in the formation of multispecies oral biofilms. With the rise of antibiotic resistance, new strategies to reduce microbial growth need to be found.
View Article and Find Full Text PDFBackground: Antibiotics are commonly used in human neonates, but their impact on neonatal T cell immunity remains poorly understood. The aim of this study was to investigate the impact of the antibiotic piperacillin with the beta-lactamase inhibitor tazobactam on neonatal CD4+ and CD8+ T cell responses to Streptococcus pneumoniae.
Methods: Splenic and lung cells were isolated from the neonatal mice receiving piperacillin and tazobactam or saline (sham) and cultured with S.
and are genetically closely related and both frequently colonise the naso-oropharynx, yet is a common cause of invasive infections whereas is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of and strains to complement-mediated immunity, demonstrating strains were susceptible to complement-mediated opsonophagocytosis.
View Article and Find Full Text PDFBackground: This study aimed to evaluate the prognostic significance of expression levels of involucrin (IVL), cytokeratin (CK)-10 and -13 at different intratumor sites (tumor center and invading area) of oral tongue squamous cell carcinoma (OTSCC).
Methods: IVL, CK13 and CK10 expression levels were examined in a multicenter cohort of 146 OTSCCs using immunohistochemistry. External mRNA datasets were used for expression analysis and/or to validate survival associations.
Recent studies have identified a clinical isolate of the commensal that expresses serotype 5 capsule ( serotype 5) and shows serospecificity toward pneumococcal serotype 5. However, it remains unknown whether serotype 5 induces protective immunity against pneumococcal serotype 5. In this study, we evaluated the ability of serotype 5 to generate protective immunity in a mouse model of lung infection with pneumococcal serotype 5.
View Article and Find Full Text PDFThe study of resistomes using whole metagenomic sequencing enables high-throughput identification of resistance genes in complex microbial communities, such as the human microbiome. Over recent years, sophisticated and diverse pipelines have been established to facilitate raw data processing and annotation. Despite the progress, there are no easy-to-use tools for comprehensive visual, statistical and functional analysis of resistome data.
View Article and Find Full Text PDFIntroduction: Antibiotic treatment in premature infants is often empirically prescribed, and practice varies widely among otherwise comparable neonatal intensive care units. Unnecessary and prolonged antibiotic treatment is documented in numerous studies. Recent research shows serious side effects and suggests long-term adverse health effects in prematurely born infants exposed to antibiotics in early life.
View Article and Find Full Text PDFAlthough antibiotics confer significant health benefits in treating or preventing bacterial infections, an accumulating wealth of evidence illustrates their detrimental effect on host-microbiota homeostasis, posing a serious menace to the global public health. In recent years, it is becoming evident that infants, who are subjected to frequent antibiotic exposures due to their vulnerability to infection, reflect increased susceptibility to a wide spectrum of diseases, including infection, in later life. Antibiotics induce perturbations of the microbiota or dysbiosis, which in turn alters the host immune responses against pathogens.
View Article and Find Full Text PDFCyclic di-adenosine monophosphate (c-di-AMP) has emerged as an important bacterial signaling molecule that functions both as an intracellular second messenger in bacterial cells and an extracellular ligand involved in bacteria-host cross-talk. In this study, we identify and characterize proteins involved in controlling the c-di-AMP concentration in the oral commensal and opportunistic pathogen (). We identified three known types of c-di-AMP turnover proteins in the genome of CCUG31611: a CdaA-type diadenylate cyclase as well as GdpP-, and DhhP-type phosphodiesterases.
View Article and Find Full Text PDFHelicobacter pylori (HP) infection is an established causative agent for gastric cancer. Although the oral cavity is a part of the gastrointestinal system, the presence and possible causative role of HP in oral squamous cell carcinoma (OSCC) is a subject of controversy. Therefore, the current study aimed to investigate HP infection in two cohorts of OSCC patients with different demographic characteristics, lifestyles and habitual risk factors.
View Article and Find Full Text PDFIn common with many bacterial pathogens, has a polysaccharide capsule which facilitates immune evasion and determines virulence. Recent data have shown that the closely related also expresses polysaccharide capsules including those with an identical chemical structure to capsular serotypes. We utilized atomic force microscopy (AFM) techniques to investigate the biophysical properties of and strains expressing the same capsular serotypes that might relate to differences in virulence potential.
View Article and Find Full Text PDFHere we show that mouse IgG2a and IgG1 antibodies specific for the commensal cross-react with pathogen serotypes 2 and 4, although the cross-reactivity conferred by IgG2a is stronger than that by IgG1 antibodies. These findings may be important for understanding the -induced IgG isotype responses and have consequences for the development of an effective pneumococcal vaccine.
View Article and Find Full Text PDF, a bacterium with high cariogenic potential, coordinates competence for natural transformation and bacteriocin production via the XIP and CSP pheromones. CSP is effective in inducing bacteriocin responses but not competence in chemically defined media (CDM). This is in contrast to XIP, which is a strong inducer of competence in CDM but can also stimulate bacteriocin genes as a late response.
View Article and Find Full Text PDFBoth intracellular immune sensing and extracellular innate immune sensing have been implicated in initiating macrophage proinflammatory cytokine responses to The capsule, a major virulence determinant, prevents phagocytosis, and we hypothesized that this would reduce activation of host innate inflammatory responses by preventing activation of intracellular proinflammatory signaling pathways. We investigated this hypothesis in human monocyte-derived macrophages stimulated with encapsulated or isogenic unencapsulated mutant Unexpectedly, despite strongly inhibiting bacterial internalization, the capsule resulted in enhanced inflammatory cytokine production by macrophages infected with Experiments using purified capsule material and a mutant expressing an serotype 4 capsule indicated these differences required whole bacteria and were not due to proinflammatory effects of the capsule itself. Transcriptional profiling demonstrated relatively few differences in macrophage gene expression profiles between infections with encapsulated and those with unencapsulated , largely limited to reduced expression of proinflammatory genes in response to unencapsulated bacteria, predicted to be due to reduced activation of the NF-κB family of transcription factors.
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