{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:15Z","timestamp":1792417395003,"version":"4.4.0"},"reference-count":49,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32-AI007151"],"award-info":[{"award-number":["T32-AI007151"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI151214-01A1"],"award-info":[{"award-number":["R01-AI151214-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI143910-01"],"award-info":[{"award-number":["R01-AI143910-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011082","name":"University of North Carolina School of Medicine","doi-asserted-by":"publisher","award":["TTSA039P1"],"award-info":[{"award-number":["TTSA039P1"]}],"id":[{"id":"10.13039\/100011082","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Pediatric infections with highly resistant\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (HR-Kp) disproportionately affect low-income countries where childhood malnutrition is prevalent. Malnutrition is an identified risk factor for infection with HR-Kp and other antimicrobial-resistant Enterobacterales, but the mechanistic underpinnings of this link and independence from other common exposures, like antibiotics, in children are unclear. Using a murine model of pediatric malnutrition, we found that mice fed a protein-deficient diet (PD) were more susceptible to colonization with HR-Kp at a 4-log lower challenge inoculum and developed a 3-log higher intestinal burden in comparison to adequately nourished mice. HR-Kp colonization in PD-fed mice persisted beyond 5 weeks, and colonization was transmitted to diet-matched cage mates. Antibiotic treatment resulted in similar HR-Kp colonization burdens regardless of diet, suggesting that nutrition-dependent colonization risk is driven by altered intestinal microbiota. Despite reduced dietary protein intake, intestinal amino acid content was maintained in PD-fed mice, supporting optimal HR-Kp growth. Furthermore, secondary bile acids, prototypic intestinal microbiota-derived molecules, were reduced in PD-fed mice, demonstrated an inverse correlation with HR-Kp burden\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , and partially inhibited the growth of HR-Kp\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Collectively, these findings reveal a role for dietary protein intake in determining nutrition-dependent colonization resistance to HR-Kp.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Antimicrobial-resistant\n                        <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                        are responsible for a growing mortality burden worldwide, with disproportionate rates of infection in low-income countries where childhood malnutrition is prevalent. Several publications have demonstrated high rates of intestinal colonization with antimicrobial-resistant\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        in children admitted with severe malnutrition in sub-Saharan Africa. However, numerous confounding risk factors in malnourished children (antibiotic use, healthcare exposure, and immune dysfunction) make it difficult to assess the direct impact of nutrition on\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        colonization. In this study, we utilized a novel mouse model of protein malnutrition to demonstrate that dietary protein deficiency renders mice susceptible to a higher burden of intestinal colonization at a lower inoculating dose of\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        . Furthermore, reduced microbiota-derived bile acid metabolites correlate with increased burden of colonization in protein-deficient mice. These results are the first to establish a direct mechanistic link associating dietary protein deficiency, bile acid metabolism, and intestinal colonization with antimicrobial-resistant\n                        <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00321-26","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:01:52Z","timestamp":1792414912000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Protein malnutrition facilitates intestinal colonization with highly resistant\n                    <i>Klebsiella pneumoniae<\/i>\n                    through disrupted intestinal microbial metabolism"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-6314","authenticated-orcid":true,"given":"Thomas","family":"Holowka","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]},{"id":[{"id":"https:\/\/ror.org\/05qghxh33","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Renaissance School of Medicine at Stony Brook University","place":["Stony Brook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica Feijoli","family":"Santiago","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ryk1543","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Human Development and Health, Faculty of Medicine, University of Southampton","place":["Southampton, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Xiao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mera F.","family":"Liccione","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, 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