Here, we performed a comparative genomic analysis of all available genomes of E. faecalis (n = 1591) and E. faecium (n = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of antimicrobial resistance, especially vancomycin resistance genes. Most of the analysed Enterococci were isolated from humans and less than 14% of them were from foods and animals. We analysed and detected CRISPR–Cas systems in 75.36% of E. faecalis genomes and only 4.89% of E. faecium genomes with a significant difference (p-value < 10⁻⁵). We found a negative correlation between the number of CRISPR–Cas systems and genome size (r = −0.397, p-value < 10⁻⁵) and a positive correlation between the genome %GC content and the number of CRISPR–Cas systems (r = 0.215, p-value < 10⁻⁵). Our findings showed that the presence of the anti-endonuclease ardA gene may explain the decrease in the number of CRISPR–Cas systems in E. faecium, known to deactivate the endonucleases’ protective activities and enable the E. faecium genome to be versatile in acquiring mobile genetic elements, including carriers of antimicrobial resistance genes, especially vanB. Most importantly, we observed that there was a direct association between the absence of CRISPR–Cas, the presence of the anti-CRISPR ardA gene and the acquisition of vancomycin resistance genes.

We propose the main characteristics of a new bacterium species named Nissabacter archeti strain 2134 (CSURP3445 = LT631518), isolated from pustule scalp of a 29-year-old man at hospital Archet 2, Nice, south of France.

Chronic granulomatous disease (CGD) is an inborn error of immunity that is caused by defects in any 1 of the 5 subunits (gp91phox, p47phox, p22phox, p67phox, p40phox) that form the NAD phosphate oxidase complex 2 (NOX2) or in the chaperone protein essential for reactive oxygen species (ROS) that supports its assembly. These defects lead to severely reduced phagocyte-derived ROS production. Almost 50% of patients with CGD have inflammatory bowel disease (IBD) associated with dysbiosis, and the age of IBD onset may vary according to the CGD genotype. Although we previously demonstrated that the intestinal microbiota determines colitis susceptibility in CGD mice, the underlying mechanisms remain unknown. We hypothesized that NOX2 defects are associated with distinct intestinal microbiome signatures and immune responses, which impact colitis severity. Chemical colitis susceptibility was evaluated in 2 strains of CGD mice (gp91phox–/– and p47phox–/–) with distinct microbiotas from 2 different animal facilities, while also evaluating the impact of microbiota standardization and colitogenic microbiota transfer on mucosal immune responses at the intestinal barrier. Although p47phox–/– and gp91phox–/– mice that harbored a colitogenic microbiota had increased colitis severity, the intestinal epithelial cells from p47phox–/– mice produced more ROS, which was associated with increased NOX isoform gene expression. In contrast, gp91phox–/– mice had decreased mucin production and a mucosal immune response profile suggestive of increased inflammasome activation at the intestinal barrier when compared with control and p47phox–/– mice. Our findings suggest that the microbiota impacts colitis susceptibility in a CGD genotype–specific manner, thereby potentially explaining differences in the timing of IBD onset in patients with different CGD genotypes and identifying potential novel and personalized therapeutic targets.

Chronic granulomatous disease (CGD) is an inborn error of immunity associated with a 50% prevalence of inflammatory bowel disease (IBD) for which current treatments are suboptimal due to the increased risk of infections in this population. CGD results from defects in the nicotinamide adenine dinucleotide phosphate oxidase 2 complex, leading to minimal or absent phagocyte-derived reactive oxygen species production. Patients with CGD present with recurrent infections and severe inflammatory complications, especially in the gut. These inflammatory complications have been associated with the increased systemic activation of the nucleotide-binding domain and leucine-rich-repeat–containing protein 3 (NLRP3) inflammasome and dysregulation of the T-cell compartment. However, the role of the NLRP3 inflammasome at the intestinal barrier and whether it can be targeted to treat CGD-associated IBD (CGD-IBD) remain unclear. β-Hydroxybutyrate (βHB), a ketone body produced during fasting or adherence to a ketogenic diet, can inhibit the NLRP3 inflammasome and restore T-cell balance. In this preclinical study, we demonstrated that a ketogenic diet significantly improves colitis in CGD mice, to a greater extent than in wild-type mice, by reducing NLRP3 inflammasome activity, altering the microbiota, and inducing tolerogenic immune populations at the intestinal mucosal barrier. We also showed that βHB supplementation could significantly improve colitis in CGD mice and decrease systemic inflammation. We further confirmed that, in the blood cells of humans with CGD, βHB effectively reduces the levels of cytokines associated with inflammasome activation. In conclusion, our study identified that NLRP3 inflammasome blockade using a ketogenic diet or βHB supplementation is a potential novel and safer treatment for CGD-IBD.

The widespread use of antimicrobials in poultry production exerts selective pressure for the emergence of resistant bacteria, yet molecular data on resistance determinants in Escherichia coli from commercial farms in Central Asia remain scarce. This study aimed to characterize antimicrobial resistance genes and mobile genetic elements in E. coli isolates from a layer poultry farm in the West Kazakhstan region. A total of 100 samples (cloacal swabs, fresh feces, internal organs, and wild pigeons) were collected. E. coli was isolated using selective media and confirmed by qPCR targeting the uidA gene. Forty isolates were confirmed, of which ten (25%) carried at least one resistance gene as determined by a panel of 57 primer sets. All ten isolates carrying antimicrobial resistance-associated genes (100%) harbored determinants associated with multidrug resistance. The most frequently detected genes were blaTEM (80%), aadA17 (90%), and intI1-a-marko (80%). A high prevalence of qacEΔ1 (80%) was also observed. At least one class 1 integron-associated gene was detected in all resistant isolates and those carrying both integron variants harbored the highest numbers of resistance genes (14–19). Resistance gene profiles in pigeon isolates mirrored those from poultry, suggesting wild birds as potential vectors. The correlation between detected resistance genes and farm antimicrobial use (enrofloxacin, trimethoprim/sulfonamide combinations) indicates strong selective pressure. These findings suggest that poultry farms may serve as environments supporting the persistence and dissemination of antimicrobial resistance-associated genes in E. coli and underscore the need for enhanced biosecurity and antimicrobial stewardship within a One Health framework.

Background Most tuberculosis (TB) cases in The Gambia are notified in the Greater Banjul Area (GBA). We conducted an Enhanced-Case-Finding (ECF) intervention in the GBA and determined its effect on TB incidence and ongoing TB transmission. Methods This was a cluster randomized trial in which randomly assigned intervention areas of grouped settlements received three rounds of an ECF strategy consisting of sensitization followed by auramine microscopy, whereas TB patients in control areas continued to be identified through passive case finding. The primary outcome was TB incidence rate. To exclude that an increase in notified cases, followed by a decrease in notified cases, would hide the future impact of the intervention, we tested for changes in transmission dynamics using both genetic clustering and phylodynamic methods. Results No significant difference in TB incidence rates, transmission clustering or effective reproductive number was detected between intervention and control areas. Conclusion Although we did not find evidence for decreased TB incidence nor TB transmission through the ECF strategy used, this approach is an examplar of how both classical epidemiology and genomic phylodynamics approaches can be integrated to better assess public health intervention outcomes.