Turton Jane F, Payne Zoë, Coward Amy, Hopkins Katie L, Turton Jack A, Doumith Michel, Woodford Neil
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London NW9 5EQ, UK.
Supporting Informatician, London NW9 0TA, UK.
J Med Microbiol. 2018 Jan;67(1):118-128. doi: 10.1099/jmm.0.000653. Epub 2017 Dec 5.
Klebsiella pneumoniae is a concern because of its multidrug resistance and the ability of hypervirulent types, especially capsular type K1-clonal complex 23 (K1-CC23), to cause community-acquired, life-threatening infections. Hypervirulent types carry an array of virulence genes including rmpA/rmpA2, coding for capsule up-regulation. We sought to identify isolates carrying these elements among submissions to the UK national reference laboratory during 2016.
Virulence elements and carbapenemase genes were sought by PCR or from whole genome sequences. Isolates were typed by variable number tandem repeat analysis or by multi locus sequence typing from whole genome sequences. Long read nanopore sequencing was carried out on two isolates.Results/Key findings. Twelve of 1090 isolates (1.1 %) belonged to hypervirulent K1-CC23, with one carrying blaOXA-48 (KpvST23L_OXA-48). A further 24 rmpA/rmpA2-positive isolates were detected: eight belonged to hypervirulent types of capsular types K2 and K54; and 14 belonged to 'non-hypervirulent' ST147, ST15 and ST383 and also carried carbapenemase gene(s). Virulence, heavy metal and antibiotic resistance gene contents were compared from whole genome sequences of KpvST23L_OXA-48 and one of the ST147 isolates carrying blaNDM-1. They carried 94/96 and 26/96 of the virulence genes sought, and 23/23 and 9/23 of the heavy metal resistance genes, respectively. In the ST147 isolate, rmpA/rmpA2 and the aerobactin siderophore cluster were on a large virulence plasmid together with resistance genes. The yersiniabactin cluster was widely present among carbapenemase gene-positive isolates, including among those that were rmpA/rmpA2-negative.
Our results highlight a combination of virulence and resistance genes, which could lead to untreatable invasive infections.
肺炎克雷伯菌因其多重耐药性以及高毒力菌株（尤其是荚膜型K1 - 克隆复合体23，即K1 - CC23）引发社区获得性危及生命感染的能力而备受关注。高毒力菌株携带一系列毒力基因，包括编码荚膜上调的rmpA/rmpA2。我们试图在2016年提交给英国国家参考实验室的样本中识别携带这些元件的分离株。
通过PCR或全基因组序列寻找毒力元件和碳青霉烯酶基因。通过可变数目串联重复分析或全基因组序列的多位点序列分型对分离株进行分型。对两株分离株进行了长读长纳米孔测序。
结果/主要发现：1090株分离株中有12株（1.1%）属于高毒力K1 - CC23，其中一株携带blaOXA - 48（KpvST23L_OXA - 48）。另外检测到24株rmpA/rmpA2阳性分离株：8株属于荚膜型K2和K54的高毒力类型；14株属于“非高毒力”的ST147、ST15和ST383，并且也携带碳青霉烯酶基因。比较了KpvST23L_OXA - 48和携带blaNDM - 1的一株ST147分离株全基因组序列中的毒力、重金属和抗生素抗性基因含量。它们分别携带了所寻找的94/96和部分26/96毒力基因，以及23/23和9/23重金属抗性基因。在ST147分离株中，rmpA/rmpA2和埃希菌素铁载体簇与抗性基因一起位于一个大的毒力质粒上。耶尔森菌素簇在碳青霉烯酶基因阳性分离株中广泛存在，包括那些rmpA/rmpA2阴性的分离株。
我们的结果突出了毒力和抗性基因的组合，这可能导致难以治疗的侵袭性感染。
