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从乌克兰战争受害者身上分离出的泛耐药肺炎克雷伯菌具有高毒力。

Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent.

作者信息

Ljungquist Oskar, Magda Michal, Giske Christian G, Tellapragada Chaitanya, Nazarchuk Oleksandr, Dmytriiev Dmytro, Thofte Oskar, Öhnström Valdemar, Matuschek Erika, Blom Anna M, Riesbeck Kristian

机构信息

Division of Infection Medicine, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.

Protein Chemistry, Department of Translational Medicine, Faculty of Medicine, Lund University, Malmö, Sweden.

出版信息

J Infect. 2024 Dec;89(6):106312. doi: 10.1016/j.jinf.2024.106312. Epub 2024 Oct 11.

Abstract

OBJECTIVES

Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.

METHODS

Klebsiella pneumoniae clinical isolates (n = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.

RESULTS

Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in pmrB and phoP genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant K. pneumoniae were more serum-resistant, more virulent against G. mellonella larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The iucA, peg-344, rmpA, rmpC, and rmpD genes were associated with increased virulence in animals.

CONCLUSIONS

Pandrug-resistant K. pneumoniae in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.

摘要

目的

从乌克兰医院接受治疗的战争受害者中分离出对碳青霉烯类和黏菌素耐药的肺炎克雷伯菌。问题在于这些对多种药物耐药的肺炎克雷伯菌是否具有致病性,以及在更广泛的背景下是否能够引发疾病。

方法

对37株肺炎克雷伯菌临床分离株进行抗生素耐药性检测,并进行全基因组测序(WGS)。此外,通过血清耐药性和两种不同的动物模型检测它们的致病性。

结果

发现属于序列类型(ST)23、147、307、395和512的分离株携带针对碳青霉烯类和头孢菌素的耐药基因。9株分离株在与黏菌素耐药相关的pmrB和phoP基因中存在点突变。所有细菌都具备多个毒力基因,耐黏菌素的分离株各自携带10个不同的基因。与对黏菌素敏感的细菌相比,耐黏菌素的肺炎克雷伯菌对血清的耐受性更强,对米氏蜜蜂幼虫的毒性更大,并且在小鼠体内的存活率更高。iucA、peg - 344、rmpA、rmpC和rmpD基因与动物体内毒力增加有关。

结论

乌克兰对多种药物耐药的肺炎克雷伯菌具有高毒力并保留其致病性,这突出了防止其传播扩散的必要性。

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