Melissa I Stair, Sebastian E Carrasco, Damodaran Annamalai, Ellen B Jordan, Anthony Mannion, Yan Feng, Niora Fabian, Zhongming Ge, Sureshkumar Muthupalani, JoAnn Dzink-Fox, Marine Anais Krzisch, James G Fox
{"title":"免疫力低下的 NSG 小鼠繁殖群中侵袭性、耐多种抗生素肺炎克雷伯氏菌感染的流行病学。","authors":"Melissa I Stair, Sebastian E Carrasco, Damodaran Annamalai, Ellen B Jordan, Anthony Mannion, Yan Feng, Niora Fabian, Zhongming Ge, Sureshkumar Muthupalani, JoAnn Dzink-Fox, Marine Anais Krzisch, James G Fox","doi":"10.30802/AALAS-CM-21-000088","DOIUrl":null,"url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> (<i>Kp</i>) is a gram-negative opportunistic pathogen that causes severe pneumonia, pyelonephritis, and sepsis in immunocompromised hosts. During a 4-mo interval, several NOD.<i>Cg-Prkdc<sup>scid</sup>Il2rg<sup>tm1Wjl</sup></i>/SzJ (NSG) breeders and pups in our facilities were diagnosed with <i>Kp</i> infections. An initial 6 adult and 1 juvenile NSG mice were submitted for necropsy and histologic examination because of acute onset of diarrhea and death. The evaluation revealed typhlocolitis in 2 of the mice and tritrichomoniasis in all 7. <i>Escherichia coli</i> positive for polyketide synthase (<i>pks+</i>) and <i>Kp</i> were isolated from the intestines. Given a history of sepsis due to <i>pks</i><sup>+</sup> <i>E. coli</i> in NSG mice in our facilities and determination of its antimicrobial susceptibility, trimethoprim-sulfamethoxazole (TMP-SMX) was administered to the colony in the drinking water for 4 wk. After this intervention, an additional 21 mice became ill or died; 11 of these mice had suppurative pneumonia, meningoencephalitis, hepatitis, metritis, pyelonephritis, or sepsis. <i>Kp</i> was cultured from pulmonary abscesses or blood of 10 of the mice. Whole-genome sequencing (WGS) indicated that the <i>Kp</i> isolates contained genes associated with phenotypes found in pore-forming <i>Kp</i> isolates cultured from humans with ulcerative colitis and primary sclerosing cholangitis. None of the <i>Kp</i> isolates exhibited a hyperviscous phenotype, but 13 of 14 were resistant to TMP-SMX. Antimicrobial susceptibility testing indicated sensitivity of the <i>Kp</i> to enrofloxacin, which was administered in the drinking water. Antibiotic sensitivity profiles were confirmed by WGS of the <i>Kp</i> strains; key virulence and resistance genes to quaternary ammonia compounds were also identified. Enrofloxacin treatment resulted in a marked reduction in mortality, and the study using the NSG mice was completed successfully. Our findings implicate intestinal translocation of <i>Kp</i> as the cause of pneumonia and systemic infections in NSG mice and highlight the importance of identification of enteric microbial pathogens and targeted antibiotic selection when treating bacterial infections in immunocompromised mice.</p>","PeriodicalId":10659,"journal":{"name":"Comparative medicine","volume":"72 4","pages":"220-229"},"PeriodicalIF":1.3000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413526/pdf/cm2022000220.pdf","citationCount":"0","resultStr":"{\"title\":\"The Epidemiology of Invasive, Multipleantibiotic-resistant <i>Klebsiella pneumoniae</i> Infection in a Breeding Colony of Immunocompromised NSG Mice.\",\"authors\":\"Melissa I Stair, Sebastian E Carrasco, Damodaran Annamalai, Ellen B Jordan, Anthony Mannion, Yan Feng, Niora Fabian, Zhongming Ge, Sureshkumar Muthupalani, JoAnn Dzink-Fox, Marine Anais Krzisch, James G Fox\",\"doi\":\"10.30802/AALAS-CM-21-000088\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Klebsiella pneumoniae</i> (<i>Kp</i>) is a gram-negative opportunistic pathogen that causes severe pneumonia, pyelonephritis, and sepsis in immunocompromised hosts. During a 4-mo interval, several NOD.<i>Cg-Prkdc<sup>scid</sup>Il2rg<sup>tm1Wjl</sup></i>/SzJ (NSG) breeders and pups in our facilities were diagnosed with <i>Kp</i> infections. An initial 6 adult and 1 juvenile NSG mice were submitted for necropsy and histologic examination because of acute onset of diarrhea and death. The evaluation revealed typhlocolitis in 2 of the mice and tritrichomoniasis in all 7. <i>Escherichia coli</i> positive for polyketide synthase (<i>pks+</i>) and <i>Kp</i> were isolated from the intestines. Given a history of sepsis due to <i>pks</i><sup>+</sup> <i>E. coli</i> in NSG mice in our facilities and determination of its antimicrobial susceptibility, trimethoprim-sulfamethoxazole (TMP-SMX) was administered to the colony in the drinking water for 4 wk. After this intervention, an additional 21 mice became ill or died; 11 of these mice had suppurative pneumonia, meningoencephalitis, hepatitis, metritis, pyelonephritis, or sepsis. <i>Kp</i> was cultured from pulmonary abscesses or blood of 10 of the mice. Whole-genome sequencing (WGS) indicated that the <i>Kp</i> isolates contained genes associated with phenotypes found in pore-forming <i>Kp</i> isolates cultured from humans with ulcerative colitis and primary sclerosing cholangitis. None of the <i>Kp</i> isolates exhibited a hyperviscous phenotype, but 13 of 14 were resistant to TMP-SMX. Antimicrobial susceptibility testing indicated sensitivity of the <i>Kp</i> to enrofloxacin, which was administered in the drinking water. Antibiotic sensitivity profiles were confirmed by WGS of the <i>Kp</i> strains; key virulence and resistance genes to quaternary ammonia compounds were also identified. Enrofloxacin treatment resulted in a marked reduction in mortality, and the study using the NSG mice was completed successfully. Our findings implicate intestinal translocation of <i>Kp</i> as the cause of pneumonia and systemic infections in NSG mice and highlight the importance of identification of enteric microbial pathogens and targeted antibiotic selection when treating bacterial infections in immunocompromised mice.</p>\",\"PeriodicalId\":10659,\"journal\":{\"name\":\"Comparative medicine\",\"volume\":\"72 4\",\"pages\":\"220-229\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2022-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413526/pdf/cm2022000220.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Comparative medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.30802/AALAS-CM-21-000088\",\"RegionNum\":4,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/7/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comparative medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.30802/AALAS-CM-21-000088","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/7/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
The Epidemiology of Invasive, Multipleantibiotic-resistant Klebsiella pneumoniae Infection in a Breeding Colony of Immunocompromised NSG Mice.
Klebsiella pneumoniae (Kp) is a gram-negative opportunistic pathogen that causes severe pneumonia, pyelonephritis, and sepsis in immunocompromised hosts. During a 4-mo interval, several NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) breeders and pups in our facilities were diagnosed with Kp infections. An initial 6 adult and 1 juvenile NSG mice were submitted for necropsy and histologic examination because of acute onset of diarrhea and death. The evaluation revealed typhlocolitis in 2 of the mice and tritrichomoniasis in all 7. Escherichia coli positive for polyketide synthase (pks+) and Kp were isolated from the intestines. Given a history of sepsis due to pks+E. coli in NSG mice in our facilities and determination of its antimicrobial susceptibility, trimethoprim-sulfamethoxazole (TMP-SMX) was administered to the colony in the drinking water for 4 wk. After this intervention, an additional 21 mice became ill or died; 11 of these mice had suppurative pneumonia, meningoencephalitis, hepatitis, metritis, pyelonephritis, or sepsis. Kp was cultured from pulmonary abscesses or blood of 10 of the mice. Whole-genome sequencing (WGS) indicated that the Kp isolates contained genes associated with phenotypes found in pore-forming Kp isolates cultured from humans with ulcerative colitis and primary sclerosing cholangitis. None of the Kp isolates exhibited a hyperviscous phenotype, but 13 of 14 were resistant to TMP-SMX. Antimicrobial susceptibility testing indicated sensitivity of the Kp to enrofloxacin, which was administered in the drinking water. Antibiotic sensitivity profiles were confirmed by WGS of the Kp strains; key virulence and resistance genes to quaternary ammonia compounds were also identified. Enrofloxacin treatment resulted in a marked reduction in mortality, and the study using the NSG mice was completed successfully. Our findings implicate intestinal translocation of Kp as the cause of pneumonia and systemic infections in NSG mice and highlight the importance of identification of enteric microbial pathogens and targeted antibiotic selection when treating bacterial infections in immunocompromised mice.
期刊介绍:
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.