摘要
      肺炎克雷伯菌序列类型14（ST14）和ST15在全球范围内引起了CTX-M-15和/或碳青霉烯酶生产商的爆发，但它们的系统发育和全球动力学尚不清楚。我们通过分析公共基因组的荚膜基因座（KL）、抗性组、病毒群和质粒组（n = 481）和从头序列（n = 9） 代表葡萄牙流传的主要亚系。CG14和CG15在根据KL和副基因组定义的6个主要亚群内独立进化。CG14（n = 65）分支被构造在两个大的单系亚群中，CG14-I（KL2，86%）和CG14-II（KL16，14%），它们的出现分别可以追溯到1932年和1911年。编码超广谱β-内酰胺酶（ESBL）、AmpC和/或碳青霉烯酶的基因主要在CG14-I中观察到（71%对22%）。CG15分支（n = 170）分为子条款CG15-IA（KL19/KL106，9%）、CG15-IB（可变KL类型，6%）、CG15-1IIA（KL24，43%）和CG15-IIB（KL112，37%）。大多数CG15基因组携带特定的GyrA和ParC突变，并于1989年从一个共同的祖先中出现。CTX-M-15在CG15（68%的CG15对38%的CG14）和CG15-IIB（92%）中尤其普遍。质粒组分析揭示了27个主要的质粒组（PG），包括特别普遍的和重组的F型（n = 10） ，列（n = 10） ，以及新的质粒类型。虽然blaCTX-M-15被高多样性的F型镶嵌质粒多次获得，但其他抗生素抗性基因（ARGs）被IncL（blaOXA-48）或IncC（blaCMY/TEM-24）质粒分散。我们首先证明了CG15和CG14的独立进化轨迹，以及在高度重组质粒中获得特异性KL、喹诺酮类耐药性决定区（QRDR）突变（CG15）和ARGs如何影响特定亚型（CG14-I和CG15-IIA/IIB）的扩展和多样化。
ABSTRACT
Klebsiella pneumoniae sequence type 14 (ST14) and ST15 caused outbreaks of CTX-M-15 and/or carbapenemase producers worldwide, but their phylogeny and global dynamics remain unclear. We clarified the evolution of K. pneumoniae clonal group 14 (CG14) and CG15 by analyzing the capsular locus (KL), resistome, virulome, and plasmidome of public genomes (n = 481) and de novo sequences (n = 9) representing main sublineages circulating in Portugal. CG14 and CG15 evolved independently within 6 main subclades defined according to the KL and the accessory genome. The CG14 (n = 65) clade was structured in two large monophyletic subclades, CG14-I (KL2, 86%) and CG14-II (KL16, 14%), whose emergences were dated to 1932 and 1911, respectively. Genes encoding extended-spectrum β-lactamase (ESBL), AmpC, and/or carbapenemases were mostly observed in CG14-I (71% versus 22%). CG15 clade (n = 170) was segregated into subclades CG15-IA (KL19/KL106, 9%), CG15-IB (variable KL types, 6%), CG15-IIA (KL24, 43%) and CG15-IIB (KL112, 37%). Most CG15 genomes carried specific GyrA and ParC mutations and emerged from a common ancestor in 1989. CTX-M-15 was especially prevalent in CG15 (68% CG15 versus 38% CG14) and in CG15-IIB (92%). Plasmidome analysis revealed 27 predominant plasmid groups (PG), including particularly pervasive and recombinant F-type (n = 10), Col (n = 10), and new plasmid types. While blaCTX-M-15 was acquired multiple times by a high diversity of F-type mosaic plasmids, other antibiotic resistance genes (ARGs) were dispersed by IncL (blaOXA-48) or IncC (blaCMY/TEM-24) plasmids. We first demonstrate an independent evolutionary trajectory for CG15 and CG14 and how the acquisition of specific KL, quinolone-resistance determining region (QRDR) mutations (CG15), and ARGs in highly recombinant plasmids could have shaped the expansion and diversification of particular subclades (CG14-I and CG15-IIA/IIB).

https://journals.asm.org/doi/full/10.1128/spectrum.03395-22