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。

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES
Comparative medicine Pub Date : 2022-08-01 Epub Date: 2022-07-26 DOI:10.30802/AALAS-CM-21-000088
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
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引用次数: 0

摘要

肺炎克雷伯氏菌(Kp)是一种革兰氏阴性机会性病原体,可导致免疫力低下的宿主患上重症肺炎、肾盂肾炎和败血症。在4个月的间隔期内,我们设施中的几只NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ(NSG)种鼠和幼鼠被诊断出感染了Kp。最初有 6 只成年 NSG 小鼠和 1 只幼年 NSG 小鼠因急性腹泻和死亡而被送去进行尸体解剖和组织学检查。评估结果显示,其中 2 只小鼠患有小肠结肠炎,所有 7 只小鼠均患有滴虫病。从肠道中分离出多酮合成酶(pks+)和 Kp 阳性的大肠杆菌。鉴于我们设施中的 NSG 小鼠曾因 pks+ 大肠杆菌引起败血症,并对其抗菌药敏感性进行了测定,因此在饮用水中对该群小鼠施用了三甲氧苄氨嘧啶-磺胺甲噁唑(TMP-SMX),为期 4 周。干预后,又有 21 只小鼠患病或死亡;其中 11 只小鼠患有化脓性肺炎、脑膜脑炎、肝炎、甲沟炎、肾盂肾炎或败血症。从其中 10 只小鼠的肺脓肿或血液中培养出了 Kp。全基因组测序(WGS)表明,Kp 分离物含有与从溃疡性结肠炎和原发性硬化性胆管炎患者体内培养出的成孔 Kp 分离物中发现的表型相关的基因。没有一个 Kp 分离物表现出高黏液表型,但 14 个分离物中有 13 个对 TMP-SMX 具有耐药性。抗菌药敏感性测试表明,Kp 对饮用水中添加的恩诺沙星敏感。Kp 菌株的 WGS 证实了其对抗生素的敏感性;还鉴定出了关键的毒力基因和对季氨化合物的抗性基因。恩诺沙星治疗显著降低了死亡率,使用 NSG 小鼠的研究顺利完成。我们的研究结果表明,Kp的肠道转运是导致NSG小鼠肺炎和全身感染的原因,并强调了在治疗免疫缺陷小鼠细菌感染时识别肠道微生物病原体和有针对性地选择抗生素的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Epidemiology of Invasive, Multipleantibiotic-resistant <i>Klebsiella pneumoniae</i> Infection in a Breeding Colony of Immunocompromised NSG Mice.

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.

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来源期刊
Comparative medicine
Comparative medicine 医学-动物学
CiteScore
1.90
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
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.
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