RESUMEN
Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus, sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.
Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Humanos , Percepción de Quorum/genética , Ácido N-Acetilneuramínico , Sistema Respiratorio , Proteínas BacterianasRESUMEN
The increased use of opioids by women of reproductive age has resulted in a dramatic rise in number of infants exposed to opioids in utero. Although perinatal opioid exposure (POE) has been associated with an elevated risk of infection and hospitalization later in life, the mechanism(s) by which opioids influence immune development and maturation is not fully elucidated. Alterations in the intestinal microbiota composition, which leads to changes in immune training and maturation, could be at play. Chronic opioid use in adults is associated with a proinflammatory and pathogenic microbiota composition; therefore, we hypothesized here that in utero morphine exposure could negatively affect intestinal microbiota composition, leading to alterations in immune system function. We report that a clinically-relevant model of perinatal opioid exposure, in rats, induces profound intestinal microbiota dysbiosis that is maintained into adulthood. Furthermore, microbial maturity was reduced in morphine-exposed offspring. This suggests that increased risk of infection observed in children exposed to opioids during gestation may be a consequence of microbiota alterations with downstream impact on immune system development. Further investigation of how perinatal morphine induces dysbiosis will be critical to the development of early life interventions designed to ameliorate the increased risk of infection observed in these children.
RESUMEN
At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GFâCC) and compared them to offspring fostered within the same microbiota status (CCâCC, GFâGF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GFâGF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GFâCC offspring for almost all measures. In contrast, total bacterial load did not differ between the CCâCC and GFâCC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GFâCC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.
RESUMEN
The significant increase in food allergy incidence is correlated with dietary changes in modernized countries. Here, we investigated the impact of dietary emulsifiers on food allergy by employing an experimental murine model. Mice were exposed to drinking water containing 1.0% carboxymethylcellulose (CMC) or Polysorbate-80 (P80) for 12 weeks, a treatment that was previously demonstrated to induce significant alterations in microbiota composition and function leading to chronic intestinal inflammation and metabolic abnormalities. Subsequently, the ovalbumin food allergy model was applied and characterized. As a result, we observed that dietary emulsifiers, especially P80, significantly exacerbated food allergy symptoms, with increased OVA-specific IgE induction and accelerated type 2 cytokine expressions, such as IL-4, IL-5, and IL-13, in the colon. Administration of an antibiotic regimen completely reversed the emulsifier-induced exacerbated susceptibility to food allergy, suggesting a critical role played by the intestinal microbiota in food allergy and type 2 immune responses.
Asunto(s)
Hipersensibilidad a los Alimentos , Ratones , Animales , Emulsionantes/efectos adversos , Dieta , Ovalbúmina , Polisorbatos/efectos adversos , Inflamación/inducido químicamente , Colon , Inmunidad , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
Dietary emulsifiers carboxymethylcellulose (CMC) and polysorbate-80 (P80) disturb gut microbiota, promoting chronic inflammation. Mice with minimal microbiota are protected against emulsifiers' effects, leading us to hypothesize that these compounds might provoke select pathobionts to promote inflammation. Gnotobiotic wild-type (WT) and interleukin-10 (IL-10)-/- mice were colonized with Crohn's-disease-associated adherent-invasive E. coli (AIEC) and subsequently administered CMC or P80. AIEC colonization of GF and altered Schaedler flora (ASF) mice results in chronic intestinal inflammation and metabolism dysregulations when consuming the emulsifier. In IL-10-/- mice, AIEC mono-colonization results in severe intestinal inflammation in response to emulsifiers. Exposure of AIEC to emulsifiers in vitro increases its motility and ability to adhere to intestinal epithelial cells. Transcriptomic analysis reveals that emulsifiers directly induce expression of clusters of genes that mediate AIEC virulence and promotion of inflammation. To conclude, emulsifiers promote virulence and encroachment of pathobionts, providing a means by which these compounds may drive inflammation in hosts carrying such bacteria.