Nonylphenol releases arachidonic acid in rat Sertoli cells via activation of PKA and PLA2.

In brief: The endocrine disruptor, nonylphenol (NP) increases 20:4n-6 release in Sertoli cells via PKA/cPLA2 activation. Our data show that lipid metabolism could be a target of NP-induced abnormal reproductive outcomes. Abstract: Nonylphenol (NP), an endocrine-disrupting chemical, is an environmental contaminant, and many notorious effects on male fertility have been reported in animal models and wild-type species. Here, we evaluated the effects of NP in follicle-stimulating hormone (FSH) signal transduction pathways and lipid metabolism using an in vitro model of rat Sertoli cell (SC) primary culture. Results show that an acute (1 h) SC exposure to NP (10 µM) increased the intra- and extra-cellular concentrations of free fatty acids (FFAs), mainly arachidonic acid (20:4n-6). Phosphatidylinositol seemed to be the major phospholipid source of this 20:4n-6 release by activation of the protein kinase A (PKA)/cytoplasmic phospholipase A2 (cPLA2) pathway. NP also increased diacylglycerols (DAG) levels and the expression (mRNA) of cyclooxygenase 2 (Cox2) and prostaglandin E2 (PGE2) levels. It is noteworthy that accumulation of lipid droplets took place after 24 h NP exposition, which was prevented by both a PKA inhibitor and a PLA2 inhibitor. Like FSH, NP triggers the release of 20:4n-6, which is a substrate for PGE2 synthesis via PKA/PLA2 activation. In addition, NP induces the formation of DAG, which could be required as a cofactor of the PKC-mediated activation of the COX2 inflammatory pathway. Our findings suggest that NP alters lipid homeostasis in SCs by inducing the activation of pro-inflammatory pathways that may trigger adverse effects in testis physiology over time. Concomitantly, the SC enhances the acylation of surplus FFAs (including 20:4n-6) in neutral lipids as a protective mechanism to shield itself from lipotoxicity and pro-inflammatory signals.

Dysregulation of ADAM10 shedding activity in naked mole-rat fibroblasts is due to deficient phosphatidylserine externalization.

The naked mole-rat (NMR, Heterocephalus glaber) is of significant interest to biogerontological research, rarely developing age-associated diseases, such as cancer. The transmembrane glycoprotein CD44 is upregulated in certain cancers and CD44 cleavage by a disintegrin and metalloproteinase 10 (ADAM10) regulates cellular migration. Here we provide evidence that mature ADAM10 is expressed in NMR primary skin fibroblasts (NPSF), and that ionomycin increases cell surface ADAM10 localization. However, we observed an absence of ADAM10 mediated CD44 cleavage, as well as shedding of exogenous and overexpressed betacellulin in NPSF, whereas in mouse primary skin fibroblasts ionomycin induced ADAM10-dependent cleavage of both CD44 and betacellulin. Overexpressing a hyperactive form of the Ca2+ -dependent phospholipid scramblase ANO6 in NPSF increased phosphatidylserine (PS) externalization, which rescued the ADAM10 sheddase activity and promoted cell migration in NPSF in an ADAM10-dependent manner. These findings suggest that dysregulation of ADAM10 shedding activity is due to a deficient PS externalization in NMR.

Evaluation of patients´ perspective on a multimorbidity patient-centered care model piloted in the chilean public health system.

BACKGROUND: The progressive multimorbidity explosion has challenged Chile's health systems and worldwide. The Centro de Innovación en Salud ANCORA UC implemented a new Multimorbidity Patient-Centered Care Model in Chile. OBJECTIVE: Evaluate the perspective of high-risk patients about the core elements of the model. METHODOLOGY: We conducted a cross sectional telephone-based survey that considered the application of a 13 items questionnaire. Of them, nine were Likert scale questions with scores from 1 to 7, one dichotomic question, and three open-ended questions. 231 high-risk patients who received care through the model at primary care centers participated in the study. Quantitative data were encoded, consolidated, and analyzed with the SPSS software. We performed descriptive and analytic statistics techniques to assess different variables and their potential associations. Thematic analysis was conducted for qualitative data. RESULTS: The overall score was 5.84 (range: 1 to 7), with a standard deviation of 1.25. Questions with the best scores were those related with personalized care and the primary care teams. The lowest scored was for the item regarding the continuity of care between primary nurses and inpatient care at the hospital. There was a difference in patient outcomes depending on their health center. Regarding sociodemographic characteristics, age did not significantly affect the results. CONCLUSIONS: The study reveals the perceptions about a complex multimorbidity intervention from the patient's perspective. It complements the impact on health services utilization evaluation that supports decision-makers currently scaling up a similar strategy in our country and could be considered in other countries dealing with non-communicable diseases.

Evaluation of the implementation progress through key performance indicators in a new multimorbidity patient-centered care model in Chile.

BACKGROUND: Complex health interventions involve deep organizational, structural, and cultural changes that challenge health teams and decision-makers. The explosion of chronic diseases has made the multimorbidity approach a global priority. The Centro de Innovación en Salud ANCORA UC implemented a Multimorbidity Patient-Centered Care Model in the Chilean public health system. OBJECTIVE: This study aims to evaluate the progress of the implementation of the Multimorbidity Patient-Centered Care Model in seven primary care centers through key performance indicators. METHODS: a set of indicators was designed to evaluate change management, operations, installation of new roles, and services and activities of the intervention strategy of the model. Key performance indicators were identified to monitor the implementation progress on minimal components for the model's sustainability. Each item was assigned against an expected minimum score of 67% of progress from the overall score. They were monitored twice in seven primary health centers in 2019 and 2020, which intervened 22,642 patients with the intervention. RESULTS: The results showed that six of the seven primary care centers reached the minimum implementation threshold. The main advances were in operational conditions, and those with minor progress in implementation were the clinical services. Population size, organization, coordination of the health care teams, additional training, and decision-makers support were key factors that determined the degree of progress in a complex intervention. CONCLUSION: It was possible to measure the progression of the implementation of a complex intervention through key performance indicators delivering relevant information for decision-makers that pursue a successful and faithful implementation. This study provides a valuable tool for the national scale-up of a similar model started in Chile by the Ministry of Health and other countries.

Fully home-based methyl aminolevulinate daylight photodynamic therapy for actinic keratosis of the face or scalp: A real life open study.

Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is highly efficacious for the treatment of nonhyperkeratotic actinic keratosis (AK), even when partially performed at home. To evaluate the long-term effectiveness, safety, and patient-reported outcomes of MAL DL-PDT performed completely by the patient in real life conditions. An open prospective study was conducted in Spain among patients diagnosed with at least five AK lesions on the face or the scalp. Patients received instruction and information in infographic format to perform MAL DL-PDT at home. All had been treated with 30% urea daily for 7 days before the day of MAL DL-PDT. Meteorological conditions on the day of the treatment and adverse effects were recorded. Patients underwent follow-up, and a second session of home-based MAL DL-PDT if deemed necessary, 3, 6, and 12 months after the initial treatment session. The study population consisted of 22 patients (19 men and three women, mean [standard deviation, SD] age, 72.05 [6.96] years). A complete response was observed in 47.7% of AK lesions at 3 months (p < 0.001) and 65.9% (n = 199) at 12 months (p < 0.001). Olsen grade II lesions showed the highest rate of response (76.07% at 12 months). The mean (SD) actinic keratosis area and severity index score decreased significantly from 4.99 (2.43) at baseline to 2.33 (1.01) at 12 months (p = 0.0234). Adverse effects were mild and expected. A majority of patients were "satisfied" or "very satisfied" with the treatment instruction provided (90.9%) and the treatment outcome (72.7%). MAL DL-PDT can be applied at home like any other topical treatment for AK. Our results indicate good long-term effectiveness, a high level of patient satisfaction, and no significant side effects.

Influence of serum vitamin D level in the response of actinic keratosis to ingenol mebutate.

Vitamin D (VD) serum levels, and keratinocytic basal expression of vitamin D receptor (VDR) before treatment of actinic keratoses (AK) have been previously reported as possible biomarkers of the response of AK to treatments. We intended to evaluate the association between these and other serum and immunohistochemical parameters with the response of AK to treatment with topical ingenol mebutate (IM). Twenty-five patients with AK on the head were treated with topical IM 0.015% gel once daily for 3 days. Biopsies were taken at baseline and 6 weeks after treatment. Immunohistochemical staining was performed for VDR, P53, Ki67, Aurora B, Survivin and ß-catenin. Basal serum 25(OH)D levels were determined. IM was more effective for KIN I and II AKs than in KIN III, and histological responders showed significantly higher serum VD levels (30.278 [SD 8.839] ng/mL) than nonresponders (21.14 [SD 7.079] ng/mL, p = 0.023). In addition, mean basal expression of VDR (45.63 [SD 16.105] %) increased significantly (57.92 [SD 14.738] %, p = 0.003) after treatment with IM. A significant decrease after treatment in the expression of several markers of aggressiveness and progression to squamous cell carcinoma, namely P53, Ki-67, aurora B kinase and survivin, was also observed. Our results support a relationship between VD status and the response of AK to treatment with topical IM, suggesting that its previous correction to proper serum levels in VD-deficient patients could improve the response of AK to the treatment.

[Contribution of a multimorbidity person-centered care strategy to the Comprehensive Family and Community Healthcare Model in Chile]. / Contribución de una estrategia de atención centrada en la persona con multimorbilidad al Modelo de Atención Integral de Salud Familiar y Comunitario en Chile.

BACKGROUND: The Multimorbidity Person-Centered Care Model allows to customize care according the needs of each person. AIM: To characterize the perception of health teams about the contribution of the Multimorbidity Person-Centered Care Model (MACEP) to the development of the key principles of the Comprehensive Family and Community Health Care Model (MAIS). MATERIAL AND METHODS: A qualitative collaborative study with 35 interviews and the participation of 67 professionals from the primary healthcare network. Content analysis using mixed code system with MAXQDA2020 program. RESULTS: The innovations and complex interventions that positively affect the development and implementation of the essential principles of MAIS were recognized by participants as a contribution of the central elements of MACEP. CONCLUSIONS: This contribution is an opportunity for the expeditious implementation of Family Health principles in the health network. Incorporating the vision of implementers and users, who are part of these changes, is essential. It is necessary to establish, project and evaluate innovations to identify, implement and promote learning at Health Services throughout the country.

Comparative histological and immunohistochemical changes in recurrent nodular basal cell carcinoma after photodynamic therapy.

Photodynamic therapy (PDT) is an established nonsurgical treatment for nodular basal cell carcinoma (nBCC). This study compares the clinical, histopathological, and immunohistochemical findings in recurrent nBCC after PDT versus pre-treatment (primary) nBCC. This retrospective study analyzed nodular BCCs treated with methyl aminolevulinate (MAL)-PDT at the Department of Dermatology, San Jorge Hospital (Huesca, Spain), between 2006 and 2015. Only cases in which both the primary and the recurring tumor were histologically confirmed were included in the analysis. Data on clinical, histological, and immunohistochemical variables were collected. The analysis included a total of 15 nBCCs resistant to 2 sessions of MAL-PDT: 11 (73.3%) were persistent BCCs (cure not achieved within 3 months of treatment) and 4 (26.7%) recurred in the first 2 years of follow-up. Subsequent biopsies of the 11 persistent nBCCs revealed that 9 (81.8%) retained the same histological type while the other 2 (18.2%) had another histological variant (micronodular and metatypical). Biopsy of the 4 recurring nBCCs revealed a persistent nodular subtype in all cases. MAL-PDT resulted in no changes in p53, survivin or ß-catenin expression, and trend toward increased EGFR immunostaining. Histology revealed a trend toward a dense stroma without ulceration in recurrent nBCC after PDT. Trend toward increased EGFR immunostaining, and no changes in survivin (which remained negative or mildly positive) or ß-catenin, (which remained moderately or our findings indicate that MAL-PDT does not induce histological or immunohistochemical changes that increase tumor aggressiveness.

[Yield of two mortality predictors in immunocompetent patients with community acquired pneumonia]. / Rendimiento de dos índices predictores de mortalidad (PSI y CURB-65) en pacientes adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad.

BACKGROUND: The severity of community acquired pneumonia (CAP) can be evaluated by the PSI and CURB-65 scales. However, it is unknown whether their predictive capacity varies according to the etiology of the disease. AIM: To compare the performance of these scales in adults with viral, bacterial, mixed, and no agent detected CAP. MATERIAL AND METHODS: We studied 725 patients hospitalized for CAP aged 18 to 95 years (47% females) Urinary S. pneumoniae and Legionella antigens were detected by immuno-chromatography (Binax®). Respiratory viruses and bacteria were detected by PCR in nasopharyngeal smears. The proportions of deaths, admission to the intensive care unit (ICU), and oxygen therapy were compared between mild and non-severe patients defined by PSI (I/II and I-III) and CURB-65 (1 and 1-2), according to the causative agent. RESULTS: Ten percent of patients died. A causative agent was detected in 65%. The proportion of mild and non-severe patients according to PSI and CURB-65, and of deceased patients, admitted to the ICU and with oxygen therapy was similar in the four categories per agent. There were no deaths among non-severe patients with bacterial CAP. However, 6% of patients with CAP caused by virus or without causative agents, died. No deaths occurred among mild patients with bacterial CAP. In viral CAP, no deaths occurred among patients classified as mild only by PSI. The yields of PSI were greater than those of CURB-65 in non-severe patients who died and were admitted to the ICU with bacterial and viral CAP (5 and 14%; 7 and 12% respectively, p = 0.04). CONCLUSIONS: The prognostic performance of PSI in CAP varies according to the causative agent in adults. It is higher in non-severe bacterial cases, and superior to CURB-65.

[History of child abuse among patients with bipolar disorders]. / El maltrato infantil y su rol en el curso clínico de pacientes con trastorno bipolar.

BACKGROUND: A history of child abuse is common and has a significant impact in the clinical course of patients diagnosed with bipolar disorders (BD). AIMS: To assess the frequency of child abuse experiences in patients BD type I and to evaluate its association with clinical course and cognitive functioning variables. MATERIAL AND METHODS: 117 patients with BD aged 45 ± 14 years (66% women) answered the Childhood Trauma Questionnaire (CTQ). The clinical course (illness onset, history of suicide attempts and number of hospitalizations) was obtained from medical records. Cognitive functioning was evaluated through social and non-social cognition tasks. RESULTS: 64% of participants reported some type of child abuse. This variable was associated with an early onset of the disease (Odds ratio (OR) = 3.3; p < 0.02), increased risk of suicide attempts (OR = 2.4; p < 0.04) and specific disturbances in social cognitive tasks. CONCLUSIONS: Our study supports evidence of a common history of child abuse in patients with BD. Although child abuse predicts a worse clinical course, major clinical practice guidelines, as well as research designs, do not highlight this evidence.

Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility.

The increase in male idiopathic infertility has been associated with daily exposure to endocrine disruptors chemicals (EDCs). Nevertheless, the mechanisms of action in relation to dysregulating proteins and regulatory microRNAs are unknown. We combined proteomic and miRNome analyses of mouse testis chronically exposed to low doses of a define mixture of EDCs [phthalates: bis(2-ethylhexyl), dibutyl and benzyl-butyl; 4-nonylphenol and 4-tert-octylphenol], administered in the drinking water from conception until adulthood (post-natal Day 60/75) and compared them with no-exposed control mice. We analysed fertility parameters and global changes in the patterns of mice testis proteome by 2D electrophoresis/mass spectrometry, along with bioinformatic analyses of dysregulated microRNAs, and their association with published data in human infertile patients. We detected a decrease in the potential fertility of exposed mice associated with changes in the expression of 18 proteins (10 up-regulated, 8 down-regulated). Functional analysis showed that 89% were involved in cell death. Furthermore, we found a group of 23 microRNAs/isomiRs (down-regulated) correlated with six of the up-regulated target proteins (DIABLO, PGAM1, RTRAF, EIF4E, IVD and CNDP2). Regarding this, PGAM1 up-regulation was validated by Western blot and mainly detected in Sertoli cells. Some of these microRNA/protein dysregulations were reported in human testis with spermatogenic failure. Overall, a chronic exposure to EDCs mixture in human males could potentially lead to spermatogenic failure through changes in microRNA expression, which could post-transcriptionally dysregulate mRNA targets that encode proteins participating in cell death in testicular cells. Finally, these microRNA/protein dysregulations need to be validated with other EDCs mixtures and concentrations.

The xenoestrogens biphenol-A and nonylphenol differentially regulate metalloprotease-mediated shedding of EGFR ligands.

The xenoestrogens bisphenol-A (BPA) and nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF-α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF and TGF-α. In cells lacking ADAM17 (Adam17-/- mEFs) BPA-stimulated release of HB-EGF, but not TGF-α, was strongly reduced, whereas NP-stimulated shedding of HB-EGF and TGF-α was completely abolished. Inactivation of both ADAM17 and the related ADAM10 (Adam10/17-/- mEFs) completely prevented the release of these substrates. In the absence of iRhom1, BPA- or NP-stimulated release of HB-EGF or TGF-α was comparable to wild-type control mEFs, conversely the BPA-induced release of HB-EGF was abolished in iRhom2-/- mEFs. The defect in shedding of HB-EGF in iRhom2-/- mEF cells could be rescued by overexpressing iRhom2. Interestingly, the NP-stimulated release of HB-EGF was not affected by the absence of iRhom2, suggesting that NP could potentially activate both ADAM10 and ADAM17. We tested this hypothesis using betacellulin (BTC), an EGFR-ligand that is a substrate for ADAM10. We found that NP, but not BPA stimulated the release of BTC in Adam17-/- , iRhom2-/- , or iRhom1/2-/- , but not in Adam10/17-/- cells. Taken together, our results suggest that BPA and NP stimulate the release of EGFR-ligands by differentially activating ADAM17 or ADAM10. The identification of specific effects of these endocrine disruptors on ADAM10 and ADAM17 will help to provide a better understanding of their roles in cell signaling and proinflammatory processes, and provide new potential targets for treatment of reproductive or inflammatory diseases such as asthma or breast cancer that are promoted by xenoestrogens.

Bisphenol-A and Nonylphenol Induce Apoptosis in Reproductive Tract Cancer Cell Lines by the Activation of ADAM17.

Endocrine-disruptor chemicals (EDCs), such as bisphenol A (BPA) and nonylphenol (NP), have been widely studied due to their negative effects on human and wildlife reproduction. Exposure to BPA or NP is related to cell death, hormonal deregulation, and cancer onset. Our previous studies showed that both compounds induce A Disintegrin And Metalloprotease 17 (ADAM17) activation. Here, we show that BPA and NP induce apoptosis in prostate and ovary cancer cell lines, in a process dependent on ADAM17 activation. ADAM17 knockdown completely prevented apoptosis as well as the shedding of ADAM17 substrates. Both compounds were found to induce an increase in intracellular calcium (Ca2+) only in Ca2+-containing medium, with the NP-treated cells response being more robust than those treated with BPA. Additionally, using a phosphorylated protein microarray, we found that both compounds stimulate common intracellular pathways related to cell growth, differentiation, survival, and apoptosis. These results suggest that BPA and NP could induce apoptosis through ADAM17 by activating different intracellular signaling pathways that may converge in different cellular responses, one of which is apoptosis. These results confirm the capacity of these compounds to induce cell apoptosis in cancer cell lines and uncover ADAM17 as a key regulator of this process in response to EDCs.

Differential expression and localization of ADAM10 and ADAM17 during rat spermatogenesis suggest a role in germ cell differentiation.

BACKGROUND: Extracellular metolloproteases have been implied in different process such as cell death, differentiation and migration. Membrane-bound metalloproteases of the ADAM family shed the extracellular domain of many cytokines and receptor controlling auto and para/juxtacrine cell signaling in different tissues. ADAM17 and ADAM10 are two members of this family surface metalloproteases involved in germ cell apoptosis during the first wave of spermatogenesis in the rat, but they have other signaling functions in somatic tissues. RESULTS: In an attempt to further study these two enzymes, we describe the presence and localization in adult male rats. Results showed that both enzymes are detected in germ and Sertoli cells during all the stages of spermatogenesis. Interestingly their protein levels and cell surface localization in adult rats were stage-specific, suggesting activation of these enzymes at particular events of rat spermatogenesis. CONCLUSIONS: Therefore, these results show that ADAM10 and ADAM17 protein levels and subcellular (cell surface) localization are regulated during rat spermatogenesis.

Genomic and Phylogenomic Characterization of Carbapenem-resistant Pseudomonas aeruginosa 'High-risk' Clone O4/ExoS+/ST654 Circulating in Chilean Hospitals.

INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious threat to public health. Globally, carbapenemases-producing CRPA isolates mainly belong to 'high-risk' clones; however, the molecular epidemiology of CRPA isolates circulating in Chile are scarce, where this pathogen is the main aetiological agent of ventilator-associated pneumonia. OBJECTIVES: To characterize the phylogenomics and molecular features of ST654 CRPA isolates collected in Chile between 2016 and 2022. METHODS: Eighty-nine CRPA isolates collected in different Chilean hospitals from clinical specimens between 2005 and 2022 were analysed. Antibiotic susceptibility tests and carbapenemases production were carried out on the CRPA ST654 isolates. Also, they were subjected to whole-genome sequencing, from which in silico analyses were performed. RESULTS: Thirty-four strains (38.2%) belonged to the ST654 high-risk clone, being the most predominant lineage of the collection. Most of these isolates belonged to a subclade including KPC producers that also clustered with strains from Argentina and the United States, whereas few VIM and NDM co-producers clustered in two different smaller subclades. The isolates exhibited a broad resistome encompassing genes mediating resistance to several other clinically relevant drugs. Additionally, all the 34 ST654 isolates were ExoS+ as a virulence factor and associated to the O4-serotype. CONCLUSIONS: Our report represents the most comprehensive phylogenomic study of a CRPA high-risk clone ST654 to date. Our analyses suggest that this lineage is undergoing a divergent evolutionary path in Chile, because most of the isolates were KPC producers and were O4 serotype, differing from previous descriptions, which underline the relevance of performing molecular surveillance on this pathogen.

Evaluation of a Transitional Care Strategy Implemented in Adults With High-Risk and Multimorbidity in Chile.

OBJECTIVES: Fragmentation of continuity of care impacts the health system's efficiency and increases inequity. It severely affects high-risk patients with multimorbidity, requiring coordinated care to avoid preventable complications. The Centro de Innovación en Salud ANCORA UC, together with the Servicio de Salud Metropolitano Sur Oriente, and the National Health Fund, implemented a transitional care strategy for high-risk adults with multimorbidity at 3 hospitals in the southeast of Santiago. The study aimed to evaluate the impact on length of hospital stay, consultations with primary care physicians and contacts after discharge, and also to describe the implementation process of the transition nurse activities. METHODS: A cohort study was performed between 2017 and 2019, with 137 hospitalizations from exposed patients and 167 hospitalizations from unexposed patients. The results of the study showed a significant decrease in the length of hospital stays and an increase in consultations with physicians. RESULTS: The results of the implementation process showed that the transition nurse followed-up in a mean of 24 hospitalizations monthly, and 91% of the discharged patients were contacted via the telephone within 7 days. The implementation process showed that the transition nurse's tasks merged with the daily clinical activities in which training on case management, transition care, and continuous support were key aspects of success. CONCLUSION: We conclude that transitional care intervention has a strong potential in addressing fragmentation of care and is feasible to install and sustain over time in the Chilean context. Finally, this study provides a detailed description of the intervention strategy contributing to its spread and scale-up.

Multiple clonal transmissions of clinically relevant extended-spectrum beta-lactamase-producing Escherichia coli among livestock, dogs, and wildlife in Chile.

OBJECTIVES: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) are a main cause of human deaths associated with antimicrobial resistance (AMR). Despite hundreds of reports of the faecal carriage of ESBL-E. coli in domestic and wild animals, the dynamics of its circulation remains poorly understood. METHODS: We used whole genome sequencing of 19 ESBL-E. coli previously isolated in the same local setting from dogs, livestock, and a wild rodent in Central Chile to assess potential cross-species transmission of ESBL-E. coli. RESULTS: Isolates harboured a large number of AMR (n = 95) and virulence (n = 45) genes, plasmids replicons (n = 24), and E. coli sequence types including top extraintestinal pathogenic E. coli ST410, ST58, ST88, and ST617. Almost identical clones (<50 single nucleotide polymorphisms difference, same antibiotic and heavy metal resistance genes, virulence genes, and plasmids) were found in faeces of dogs, cattle, or sheep from the same farm, and in a dog and a wild rodent living in proximity. CONCLUSIONS: To our knowledge, this is the first report of multiple clonal cross-species transmission of ESBL-E. coli in domestic and potentially wild animals of Latin America. Our results suggest that relatively rare spread of AMR across animal species can still occur by both clonal and plasmid dissemination. Our study highlights the need for establishing preventive measures to limit the circulation of these bacteria among animals in agricultural settings, particularly given the highly pathogenic profile of several E. coli strains detected in these animals.