ESBL Escherichia coli Isolates Have Enhanced Gut Colonization Capacity Compared to Non-ESBL Strains in Neonatal Mice.

ESBL Escherichia coli Isolates Have Enhanced Gut Colonization Capacity Compared to Non-ESBL Strains in Neonatal Mice.
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DOI:
10.1128/spectrum.00582-22
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发表时间:
2022-10-26
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学1区
文献类型:
--
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产超广谱β-内酰胺酶(ESBL)的大肠埃希菌可引起婴儿和免疫低下儿童的侵袭性感染,相关发病率和死亡率较高。肠道是社区中这些菌株的主要储存库。目前的教条规定,抗菌素耐药性与健康成本有关。然而,最近的数据显示,与非耐药的大肠杆菌菌株相比,当代的一些ESBL大肠杆菌菌株可能更适合。在这里,我们首先使用全基因组测序的方法对从巴基斯坦社区婴儿中分离的15株ESBL大肠杆菌、1株临床肠外致病性ESBL大肠杆菌ST131菌株和1株非ESBL共生大肠杆菌进行鉴定,然后使用一种新的早期肠道定植动物模型来评估这些菌株在幼鼠肠道的定植能力。我们确定CTX-M-15在所有ESBL菌株中都存在,以及额外的β-内酰胺酶和与多种抗生素类耐药相关的基因。在动物模型中,11/16 ESBL大肠杆菌菌株在出生第四周时的定植负担明显高于共生菌株,即使在没有选择性抗生素压力的情况下也是如此,这表明这些菌株尽管具有高度的抗菌素耐药性,但可能具有更强的适应性。重要性抗菌素耐药性是一种全球公共卫生紧急情况。婴儿,特别是早产儿和新生儿重症监护病房中的婴儿、免疫功能低下的宿主和患有慢性病的婴儿,因抗菌素耐药菌株侵入性感染而产生不良后果的风险最高。长期以来,人们一直认为耐药性与适应成本有关,即抗菌素耐药菌株不能像非耐药菌株那样在肠道中定植,而抗生素暴露是耐药菌株持续定植的关键风险因素。在这里,我们使用一种新的幼鼠模型来增加越来越多的文献,即一些高度耐药的当代大肠杆菌菌株可以在肠道中存活,并带来很大的定植负担,尽管没有接触抗生素。
Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli can cause invasive infections in infants and immunocompromised children with high associated morbidity and mortality. The gut is a major reservoir of these strains in the community. Current dogma dictates that antimicrobial resistance is associated with a fitness cost. However, recent data show that some contemporary ESBL E. coli strains may be more “fit” compared to nonresistant E. coli strains. Here, we use whole-genome sequencing to first characterize 15 ESBL E. coli strains isolated from infants in a Pakistani community, a clinical extraintestinal pathogenic ESBL E. coli ST131 strain, and a non-ESBL commensal E. coli strain, and then use a novel animal model of early life gut colonization to assess the ability of these strains to colonize the infant mouse gut. We determined that CTX-M-15 was present in all the ESBL strains, as well as additional beta-lactamases and genes conferring resistance to multiple antibiotic classes. In the animal model, 11/16 ESBL E. coli strains had significantly higher burden of colonization at week four of life compared to commensal strains, even in the absence of selective antibiotic pressure, suggesting that these strains may have enhanced fitness despite being highly antimicrobial resistant. IMPORTANCE Antimicrobial resistance is a global public health emergency. Infants, especially preterm infants and those in the neonatal intensive care unit, immunocompromised hosts, and those with chronic illnesses are at highest risk of adverse outcomes from invasive infections with antimicrobial-resistant strains. It has long been thought that resistance is associated with a fitness cost, i.e., antimicrobial-resistant strains are not able to colonize the gut as well as nonresistant strains, and that antibiotic exposure is a key risk factor for persistent colonization with resistant strains. Here, we use a novel infant mouse model to add to the growing body of literature that some highly-resistant contemporary Escherichia coli strains can persist in the gut with a significant burden of colonization despite absence of antibiotic exposure.
DOI: 10.1128/aac.00635-19
发表时间: 2019-08-01
影响因子: 4.9
作者:
Billard-Pomares, Typhaine;Clermont, Olivier;Branger, Catherine
通讯作者: Branger, Catherine
DOI: 10.1074/jbc.m703580200
发表时间: 2007-08-24
影响因子: 4.8
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Hines, Justin K.;Kruesel, Claire E.;Honzatko, Richard B.
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发表时间: 2017-02-01
影响因子: 2.9
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通讯作者: Kushnir, Amir
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发表时间: 2018-02-22
影响因子: 1.9
作者:
Challita, Caren;Hafza, Nourhane;Daoud, Ziad
通讯作者: Daoud, Ziad
DOI: 10.1086/597512
发表时间: 2009-06
影响因子: 4.5
作者:
Litzow JM;Gill CJ;Mantaring JB;Fox MP;MacLeod WB;Mendoza M;Mendoza S;Scobie R;Huskins CW;Goldman DA;Hamer DH
通讯作者: Hamer DH