Modelling the gastrointestinal carriage of Klebsiella pneumoniae infections
Modelling the gastrointestinal carriage of Klebsiella pneumoniae infections
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肺炎克雷伯菌感染的胃肠道运输模型
DOI：
10.1101/2022.10.03.510744
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Calderon-Gonzalez R
中科院分区：
文献类型：
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作者：
Calderon-Gonzalez R
肺炎克雷伯菌是医院和社区获得性感染的主要原因，使肺炎克雷伯菌成为与任何抗生素耐药感染导致的第二大死亡人数相关的病原体。肺炎克雷伯菌以无症状的方式在鼻咽和胃肠道定植，而不会传播到其他组织。重要的是，胃肠道定植是感染的必要条件。我们对肺炎克雷伯菌定植的理解仍然基于对小鼠模型的询问，在小鼠模型中，动物预先使用抗生素来干扰肠道微生物群施加的定植抗性。在这些模型中，感染传播到其他组织。在这里，我们报告了一个小鼠模型，允许胃肠道定植肺炎克雷伯菌没有组织传播的研究。在没有抗生素治疗的近交小鼠群体中，高毒力和抗生素耐药菌株稳定地定植在胃肠道。小肠是主要的定植部位，然后随着时间的推移过渡到结肠，而不会扩散到其他组织。我们的模型概括了转移性肺炎克雷伯菌菌株的疾病动力学，这些菌株能够从胃肠道传播到其他无菌部位。定植与轻度至中度组织病理学有关，没有明显的炎症，对微生物组的丰富度没有影响。我们的模型总结了抗生素治疗扰乱肺炎克雷伯菌定植并导致传播到其他组织的临床情况。最后，我们确定胶囊多糖是大肠定植所必需的，而VI型分泌系统有助于胃肠道的定植。肺炎杆菌是在抗生素耐药性大流行中席卷全球的病原体之一。克雷伯菌以无症状的方式在健康受试者的鼻咽和肠道中定植，使肠道定植成为感染的必要条件。这使得了解胃肠道运输对预防克雷伯氏菌感染至关重要。目前的研究模型依赖于抗生素对肠道微生物群的干扰，导致侵袭性感染。在这里，我们报告了一种新的肺炎克雷伯菌肠道定植模型，它概括了无症状人类胃肠道定植的关键特征。在我们的模型中，不需要干扰微生物群来实现稳定的定植，也不会向其他组织传播。我们的模型总结了抗生素治疗引发侵袭性感染的临床情况。我们设想我们的模型将成为一个很好的平台，在此平台上研究增强定植和侵袭性感染的因素，并测试消除克雷伯氏菌无症状定植的治疗方法。
Klebsiella pneumoniae is a leading cause of nosocomial and community acquired infections, making K. pneumoniae the pathogen that is associated with the second largest number of deaths attributed to any antibiotic resistant infection. K. pneumoniae colonizes the nasopharynx and the gastrointestinal tract in an asymptomatic manner without dissemination to other tissues. Importantly, gastrointestinal colonization is a requisite for infection. Our understanding of K. pneumoniae colonization is still based on interrogating mouse models in which animals are pretreated with antibiotics to disturb the colonization resistance imposed by the gut microbiome. In these models, infections disseminate to other tissues. Here, we report a murine model to allow for the study of the gastrointestinal colonization of K. pneumoniae without tissue dissemination. Hypervirulent and antibiotic resistant strains stably colonize the gastrointestinal tract of in an inbred mouse population without antibiotic treatment. The small intestine is the primary site of colonization and is followed by a transition to the colon over time, without dissemination to other tissues. Our model recapitulates the disease dynamics of the metastatic K. pneumoniae strains that are able to disseminate from the gastrointestinal tract to other sterile sites. Colonization is associated with mild to moderate histopathology, no significant inflammation, and no effect on the richness of the microbiome. Our model sums up the clinical scenario in which antibiotic treatment disturbs the colonization of K. pneumoniae and results in dissemination to other tissues. Finally, we establish that the capsule polysaccharide is necessary for the colonization of the large intestine, whereas the type VI secretion system contributes to colonization across the gastrointestinal tract.IMPORTANCEKlebsiella pneumoniae is one of the pathogens that is sweeping the world in the antibiotic resistance pandemic.Klebsiellacolonizes the nasopharynx and the gut of healthy subjects in an asymptomatic manner, making gut colonization a requisite for infection. This makes it essential to understand the gastrointestinal carriage in preventing Klebsiella infections. Current research models rely on the perturbation of the gut microbiome by antibiotics, resulting in an invasive infection. Here, we report a new model of K. pneumoniae gut colonization that recapitulates key features of the asymptomatic human gastrointestinal tract colonization. In our model, there is no need to disturb the microbiota to achieve stable colonization, and there is no dissemination to other tissues. Our model sums up the clinical scenario in which antibiotic treatment triggers invasive infection. We envision that our model will be an excellent platform upon which to investigate factors enhancing colonization and invasive infections and to test therapeutics to eliminate Klebsiella asymptomatic colonization.