Evidence of transmission and dissemination of diverse <i>bla</i> _NDM-5 -producing <i>Escherichia coli</i> clones between refugee and host communities and their environment: a multicenter cross-sectional study

ABSTRACT The global spread of carbapenemase-producing Escherichia coli (CP-Ec) poses a significant public health threat, with particularly severe consequences for vulnerable populations in resource-limited settings. To address this, we conducted in-depth genetic analyses and examined the relatedness of CP-Ec isolates recovered from hospitalized patients, refugees, animals, water, and environmental sources within refugee camps and in marginalized host communities in Lebanon. Nineteen putative CP-Ec isolates, identified by MALDI-TOF MS and designated as community isolates, harbored either NDM ( n = 17) or OXA-48-like ( n = 2) carbapenemases. We used whole-genome sequencing (WGS) to characterize the resistomes and sequence types of these isolates. To further examine genetic relationships and transmission dynamics, we also analyzed publicly available (EnteroBase) CP-Ec genomes from Lebanon ( n = 64) and across the globe ( n = 447 recovered in 2022) alongside 31 additional clinical CP-Ec isolates from the same geographic region. The community isolates belonged to ST10, ST167, ST361, ST410, ST617, ST648, ST940, ST1284, and ST5842. Both community and clinical CP-Ec isolates carried multiple acquired antimicrobial resistance (AMR) genes and chromosomal mutations, with 82% harboring the bla NDM-5 gene. Core-genome SNP analysis showed that refugee isolates clustered with global CP-Ec genomes, highlighting their genomic relatedness and potential for geographical dissemination. Furthermore, integration of our data with previously reported Lebanese genomes demonstrated the spread of bla NDM-5 -carrying E. coli across different hosts and niches, emphasizing the complex interplay of AMR within the human-animal-environment interface. The coexistence of carbapenemase genes with mobile genetic elements that enable horizontal gene transfer raises concerns about the emergence of highly resistant and hypervirulent CP-Ec lineages, especially in vulnerable populations and settings. IMPORTANCE The global rise of CP-Ec strains harboring bla NDM-5 has been increasingly documented in clinical settings. However, little is known about their emergence and transmission in refugee settlements. This study provides a high-resolution genomic characterization of CP-Ec isolated from human, animal, water, and environmental sources in refugee settlements and surrounding host communities. By integrating whole-genome sequencing data from clinical isolates collected in Lebanese hospitals, we reveal genetically related strains in both community and healthcare settings, highlighting the potential introduction of community-acquired strains into clinical environments and vice versa. The widespread detection of bla NDM-5 across multiple reservoirs suggests sustained circulation beyond hospital settings. The identification of CP-Ec in river water used for irrigation and emptying into the Mediterranean Sea highlights wider environmental dimensions that may drive regional dissemination of AMR. Our findings highlight the urgent need for One Health-based AMR surveillance strategies to track the spread of carbapenem-resistant pathogens in high-risk settings.