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上海地区儿童患者中流行的肺炎克雷伯菌菌株的分子流行病学和对碳青霉烯类耐药的肺炎克雷伯菌感染的体液抗体反应。

The Molecular Epidemiology of Prevalent Klebsiella pneumoniae Strains and Humoral Antibody Responses against Carbapenem-Resistant K. pneumoniae Infections among Pediatric Patients in Shanghai.

机构信息

Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Clinical Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

mSphere. 2022 Oct 26;7(5):e0027122. doi: 10.1128/msphere.00271-22. Epub 2022 Sep 7.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has caused wide dissemination among pediatric patients globally and thus has aroused public concern. Here, we investigated the clinical epidemiological characteristics of 140 nonreplicate clinical K. pneumoniae strains isolated from pediatric patients between January and December 2021. Of all isolates, 16.43% (23 of 140) were CRKP strains, which predominantly contained KPC carbapenemase. sequencing demonstrated that KL47 (65.22%, 15 of 23) was the most frequent capsular type, followed by KL64 (17.39%, 4 of 23). A total of 23 CRKP strains were classified into three different O-genotypes, including OL101 (65.22%, 15 of 23), O1 (26.09%, 6 of 23), and O3 (8.7%, 2 of 23). Interestingly, KL47 strains were strongly associated with OL101, while KL64 strains were all linked with O1. Some capsule-deficient strains were identified by serological typing, phage-typing, depolymerase-typing, and uronic acid assay. In this study, compared with healthy children, higher titers of anti-capsular polysaccharides (CPS) IgG were first detected in the sera of K47 and K64 K. pneumoniae-infected children, which had the effective bactericidal activity against corresponding serotype K. pneumoniae strains. These findings will facilitate the development of novel therapeutic and vaccine strategies against K. pneumoniae infection in children. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains resistant to numerous antibiotics and the limited therapeutic options available have become an urgent health threat to the immunocompromised pediatric population. Vaccines and antibodies, especially those targeting capsular polysaccharides, may be novel and effective prevention and treatment options. Thus, it is important to understand the spread of CRKP in pediatric populations. This research presents OL101:KL47 and O1:KL64 as the predominant combinations among CRKP strains in children in Shanghai, China. The primary carbapenemase gene is KPC in CRKP strains. Additionally, this study found elevated levels of anti-CPS IgG against K47 and K64 K. pneumoniae strains in pediatric patients for the first time. The significant bactericidal activity of these anti-CPS IgGs was confirmed.

摘要

耐碳青霉烯肺炎克雷伯菌(CRKP)在全球范围内已广泛传播于儿科患者中,引起了公众的广泛关注。在此,我们对 2021 年 1 月至 12 月期间从儿科患者中分离的 140 株非重复临床肺炎克雷伯菌进行了临床流行病学特征研究。所有分离株中,16.43%(23/140)为耐碳青霉烯肺炎克雷伯菌,主要含有 KPC 碳青霉烯酶。 测序表明 KL47(65.22%,23/23)是最常见的荚膜型,其次是 KL64(17.39%,23/23)。23 株耐碳青霉烯肺炎克雷伯菌可分为 3 种不同的 O 型,包括 OL101(65.22%,23/23)、O1(26.09%,23/23)和 O3(8.7%,23/23)。有趣的是,KL47 株与 OL101 密切相关,而 KL64 株均与 O1 相关。荚膜缺失株通过血清学分型、噬菌体分型、解聚酶分型和糖醛酸测定进行鉴定。在本研究中,与健康儿童相比,首次在 KL47 和 KL64 肺炎克雷伯菌感染儿童血清中检测到针对荚膜多糖(CPS)IgG 的更高滴度,这些 IgG 对相应血清型肺炎克雷伯菌菌株具有有效的杀菌活性。这些发现将有助于开发针对儿童肺炎克雷伯菌感染的新型治疗和疫苗策略。耐碳青霉烯肺炎克雷伯菌(CRKP)菌株对多种抗生素的耐药性以及有限的治疗选择已成为免疫功能低下的儿科人群的紧迫健康威胁。疫苗和抗体,特别是针对荚膜多糖的疫苗和抗体,可能是新的有效预防和治疗选择。因此,了解 CRKP 在儿科人群中的传播情况非常重要。本研究表明,在中国上海的儿童中,CRKP 菌株以 OL101:KL47 和 O1:KL64 为主。CRKP 菌株的主要碳青霉烯酶基因是 KPC。此外,本研究首次发现儿科患者对 KL47 和 KL64 肺炎克雷伯菌的 CPS IgG 水平升高。这些抗 CPS IgG 的显著杀菌活性得到了证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c61e/9599505/f03421891880/msphere.00271-22-f001.jpg

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