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BackgroundThe spread of antibiotic-resistant bacteria may be driven by human-animal-environment interactions, especially in regions with limited restrictions on antibiotic use, widespread food animal production, and free-roaming domestic animals. In this study, we aimed to identify risk factors related to domestic animals, backyard food animals, and commercial food animal production in Ecuadorian communities.Methods & FindingsWe conducted a repeated-measures study from 2018-2021 in 7 semi-rural parishes of Quito, Ecuador to identify determinants of third-generation cephalosporin-resistantE. coli(3GCR-EC) and extended-spectrum beta-lactamaseE. coli(ESBL-EC) in children and domestic animals. We used multivariable log-binomial regression models to estimate relative risks (RR) of 3GCR-EC and ESBL-EC carriage. We collected 1,699 child fecal samples from 600 households and 1,871 animal fecal samples from 376 of the same households. Risk factors for 3GCR-EC included living within 5 km of more than 5 commercial food animal operations (RR: 1.36; 95% Confidence Interval: 1.16, 1.59), household pig ownership (1.23; 1.02, 1.48), child pet contact (1.23; 1.09, 1.39), and rarely/never washing hands after contact with animals (1.15; 0.98, 1.34). Risk factors for ESBL-EC were dog ownership (1.43; 1.00, 2.04), child pet contact (1.54; 1.10, 2.16), placing animal feces on household land/crops (1.63; 1.09, 2.46), and combined exposures to both household food animals and commercial food animal operation drainage paths (1.80; 0.94, 3.45).ConclusionsPolicies and interventions that improve the safety of animal waste management in communities and in commercial food animal production operations may be necessary to curb the spread of resistant bacteria.

The gastrointestinal tract constitutes a complex and diverse ecosystem. Escherichia coli is one of the most frequently studied and characterized species in the gut ecosystem, nevertheless, there has been little research to determine their diversity and population dynamics in the intestines of children over time. In this prospective study, a fresh fecal sample was obtained from children longitudinally over one year (30 fecal samples at sampling period 1 and 22 fecal samples at sampling periods 2 and 3). From each stool sample, five E. coli colonies were randomly selected (n = 405 E. coli isolates total) in order to characterize the genotype and phenotypic antimicrobial resistance patterns. We found that all numerically dominant E. coli lineages in children’s intestines were transient colonizers, and antimicrobial resistance phenotypes of these strains varied significantly over time without any apparent selective force. Whole-genome sequencing of 3 isolates belonging to ST131 found in one child during the sampling period I and II indicated that isolates were three different ST 131 clones that carried extended-spectrum β-lactamase (ESBL) genes.IMPORTANCEThe length of residency and numeric dominance of antimicrobial-resistant E. coli may affect the extent to which an isolate contributes to the dissemination of antimicrobial resistance in a community. We studied the persistence of numerically dominant and antimicrobial-resistant lineages of E. coli in the human intestine. We found that E. coli lineages in the children's gut change considerably and rapidly over time. This study suggests that some phenotypic resistance patterns may result from the random distribution of genes in E. coli populations over time and may not be associated with differential exposure to antimicrobials.

The gastrointestinal tract (GIT) constitutes a complex and diverse ecosystem. Escherichia coli is one of the most frequently studied and characterized species in the gut ecosystem. Nevertheless, there has been little research to determine their diversity and population dynamics in the intestines of children over time. Many intestinal E. coli lineages carry antimicrobial resistance and virulence genes, which have implications in disease and public health. In this one-year prospective study, a fresh fecal sample was obtained from 30 children longitudinally for one year (n = 82 fecal samples). From each stool sample, five Escherichia coli colonies were randomly selected to characterize their genotype and phenotypic antimicrobial resistance pattern (n = 405 E. coli isolates). We found that the most numerically dominant E. coli lineages in children’s intestines were transient colonizers, and phenotypic antimicrobial resistance varied significantly over time, however, ST131 a multi-drug resistant pathogen, and 3 additional STs persisted in a child’s intestine for 3 months or more.IMPORTANCEThe length of residency and numeric dominance of antimicrobial-resistant E. coli may affect the extent to which an isolate contributes to the dissemination of antimicrobial resistance. We studied the persistence of numerically dominant and antimicrobial-resistant lineages of E. coli in the human intestine and found that E. coli lineages in the gut of children change rapidly over time.

The increased prevalence of antimicrobial resistance (AMR) among Enterobacteriaceae has had major clinical and economic impacts in human medicine. Many of the multi-drug resistant (MDR) Enterobacteriaceae found in humans are community-acquired and linked to food animals (i.e. livestock raised for meat and dairy products). In this study, we examined whether numerically dominant, commensal Escherichia coli strains from humans (n=63 isolates) and domestic animals (n=174 isolates) in the same community and with matching phenotypic AMR patterns, were clonally related or shared the same plasmids. We identified 25 multi-drug resistant isolates (i.e. resistant to 3 or more antimicrobial classes) that shared identical phenotypic resistance patterns. We then investigated the diversity of E. coli clones, AMR genes and plasmids carrying the AMR genes using conjugation, replicon typing and whole genome sequencing. None of the MDR E. coli isolates (from children and domestic animals) analyzed were clonal. While the majority of isolates shared the same antimicrobial resistance genes and replicons, DNA sequencing indicated that these genes and replicons were found on different plasmid structures. Our findings suggest that nonclonal resistance gene dissemination is common in this community and that diverse plasmids carrying AMR genes presents a significant challenge for understanding the movement of AMR in a community.IMPORTANCEEven though Escherichia coli strains may share nearly identical AMR profiles, AMR genes, and overlap in space and time, the diversity of clones and plasmids challenges to research that aims to identify sources of AMR. Horizontal gene transfer appears to play a much larger role than clonal expansion in the spread of AMR in the community.

Lupus nephritis (LN) occurs in up to 50% of patients with systemic lupus erythematosus (SLE), and is a major contributor to mortality and morbidity. LN presents as a highly heterogeneous disease both in histopathology and response to therapy. The molecular and cellular processes leading to renal damage and to the heterogeneity of the disease are not well understood. To elucidate the processes underpinning the heterogeneity of LN, we applied singlecell RNA-sequencing (scRNA-seq) to renal biopsies from LN patients. Skin biopsies were evaluated as a source of biomarkers for monitoring kidney disease. Type-I interferon (IFN) response signatures were identified in tubular cells and keratinocytes, differentiating LN patients from healthy controls. Non-responders associated with higher IFN signatures in both tissue compartments. Moreover, non-response was also associated with a fibrotic signature in the tubular cells. Receptor-ligand interaction analysis indicated that the fibrotic process is likely mediated by FGF receptors with the initiating signal originating from infiltrating leukocytes. Differential expression analysis of tubular cells between proliferative and membranous LN pointed to several fibrosis-relevant pathways, which may offer insight into their histological differences. In summary, scRNA-seq was applied to LN to deconstruct its heterogeneity and provide novel targets for personalized approaches to therapy.