<p>The convergence of resistance to last-resort antibiotics in <i>Escherichia coli</i> represents a growing global threat. Yunnan, located at the edge of the Qinghai—Tibet Plateau and characterized by complex topography, monsoon climate, and highly diverse ecological niches, provides a unique setting in which the emergence of resistance in commensal reservoirs remains incompletely understood. Here, we performed selective screening of 1000 intestinal samples from healthy individuals in Yunnan, China, and identified 7.2% (72/1000) of <i>bla</i><sub>NDM</sub>-positive <i>E. coli</i> isolates. Among these, 6.9% (5/72) of isolates co-harbored additional resistance determinants, including <i>tet</i>(X4) (<i>n</i> = 3) or <i>mcr</i>-1 (<i>n</i> = 2). All co-harboring isolates exhibited multidrug-resistant phenotypes, and conjugation assays confirmed the transferability of these resistance genes. Phylogenetic analysis incorporating 2194 publicly available genomes from the NCBI database revealed that <i>bla</i><sub>NDM</sub> was distributed across diverse genetic backgrounds, supporting horizontal gene transfer as the primary driver of dissemination. Genomic context analysis further demonstrated both conserved and diverse resistance gene environments associated with mobile genetic elements. Together, these findings reveal the emergence of transferable combinations of <i>bla</i><sub>NDM</sub> with <i>tet</i>(X4) or <i>mcr</i>-1 in intestinal <i>E. coli</i>, highlighting the gut microbiota as a potential reservoir for the accumulation and spread of resistance to multiple last-resort antibiotics.</p>

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Intestinal carriage of transferable blaNDM with tet(X4) or mcr-1 in Escherichia coli from healthy individuals in Yunnan, China

  • Yi Sun,
  • Ling Liu,
  • Ling Xin,
  • Gongxiang Chen

摘要

The convergence of resistance to last-resort antibiotics in Escherichia coli represents a growing global threat. Yunnan, located at the edge of the Qinghai—Tibet Plateau and characterized by complex topography, monsoon climate, and highly diverse ecological niches, provides a unique setting in which the emergence of resistance in commensal reservoirs remains incompletely understood. Here, we performed selective screening of 1000 intestinal samples from healthy individuals in Yunnan, China, and identified 7.2% (72/1000) of blaNDM-positive E. coli isolates. Among these, 6.9% (5/72) of isolates co-harbored additional resistance determinants, including tet(X4) (n = 3) or mcr-1 (n = 2). All co-harboring isolates exhibited multidrug-resistant phenotypes, and conjugation assays confirmed the transferability of these resistance genes. Phylogenetic analysis incorporating 2194 publicly available genomes from the NCBI database revealed that blaNDM was distributed across diverse genetic backgrounds, supporting horizontal gene transfer as the primary driver of dissemination. Genomic context analysis further demonstrated both conserved and diverse resistance gene environments associated with mobile genetic elements. Together, these findings reveal the emergence of transferable combinations of blaNDM with tet(X4) or mcr-1 in intestinal E. coli, highlighting the gut microbiota as a potential reservoir for the accumulation and spread of resistance to multiple last-resort antibiotics.