Epidemiology of carbapenem-resistant Klebsiella pneumoniae ST15 of producing KPC-2, SHV-106 and CTX-M-15 in Anhui, China

Abstract

Background: It is well known that carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a more problematic public health issue due to its widespread spread worldwide. In China, ST11-type CRKP is the most prevalent CRKP, but ST15-type CRKP, a recently prevalent high-risk clone, has emerged widely throughout China, posing a serious public health risk. Therefore, we conducted an epidemiological of an outbreak of ST15 CRKP of producing CTX-M-15, KPC-2 and SHV-106 in a tertiary hospital in Anhui, China, to Understanding the potential risks of the current STT15 CRKP outbreak. Results: From July 2021 to December 2021, 13 ST15 CRKP isolates were identified by collecting non-repeated clinical multidrug-resistant isolates, with all capsular typing of serotype KL19. All ST15 CRKP isolates were resistant to cephalosporins, carbapenems and quinolones, but were sensitive to amikacin, tigecycline and polymyxin B. In addition, isolates carried blaSHV−106 (100%), blaKPC−2 (69%), blaCTX−M−15 (69%), blaTEM−1B (69%), blaOXA−1 (62%) and blaLAP−2 (8%), as well as iron chelators (iutA, ybt, fyuA, ent, fepA, irp1, irp2, 100%) were detected. In phenotyping experiments, all ST15 CRKP exhibited lower growth rates than NTUH-K2044, and all ST15 CRKP did not exhibit mucoviscositty characteristics. However, in the Galleria mellonella infection model, isolates 21081212, 21081241 and 21091216 were more lethal than the hypervirulent isolates NTUH-K2044. Sequencing results showed that the genetic environment surrounding the genes blaSHV−106, blaKPC−2, blaCTX−M−15, blaOXA−1 and blaTEM−1B were all identical in the ST15 CRKP isolates. Phylogenetic analysis showed that 13 ST15 CRKP isolates were divided into three subgroups, and when placed in global analysis, 10 of them were highly homologous to isolates from Jiangsu, two were highly homologous to isolates from Zhejiang, and one was homologous to an isolate from an unlabelled region. Conclusion: Our research shows that ST15 CRKP, which carries multiple β-lactamases genes and siderophores-encoding genes, may be evolving to hypervirulence and may have spread widely in localised areas. Therefore, environmental surveillance and clinical infection control in hospitals should be strengthened to prevent further spread of ST15 CRKP.

Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study

“…However, this study found that the MIC of imipenem was 2-16mg/L, lower than that of meropenem (4-32mg/L), which may be related to the presence of membrane protein genes (OmpK35/36/37). The antibiotic susceptibility and resistance genes of ST15-type strains reported in the study also differ from previous reports ( Hu et al., 2013 ; Han et al., 2021 ; Zhao et al., 2022 ). Most ST15 OXA-232-producing CRKP strains in previous studies co-produce CTX-M-15 , KPC-2 and NDM-1 , while our strains carry three more AMR genes, including CTX-M-1 , SHV-28 and TEM-1 genes, as well as the aminoglycoside resistance gene 16S rRNA methylase rmtF .…”

Prevalence of multidrug-resistant hypervirulent Klebsiella pneumoniae without defined hypervirulent biomarkers in Anhui, China: a new dimension of hypervirulence

“…When analyzed SNPs in 22122315 (ST15), it was compared with recently reported ST15 isolates ( Zhao et al, 2022 ). Considering all SNPs in the coding DNA sequence (CDS) region, we identified 36 common mutations, including 1 stop lost.…”

“… Distribution of single nucleotide polymorphisms (SNPs) in hypervirulent isolate 22122315 that causes missense mutations compared to previous ST15 isolates ( Zhao et al 2022 ). Here, presence or absence of missense mutations in CDS region (green), start codon (blue) and stop codon (red) are represented in different colors.…”

“…Multi-locus sequence typing (MLST) and capsular K-typing of all clinical hvKp isolates were determined by previously described PCR amplification methods with some modifications ( Zhao et al, 2022 ). First, extract the whole genome from overnight bacterial culture following the manufacturer’s protocol with minor changes (GenStar).…”

“…Because carbapenem-resistant hvKp strains may cause severe, untreatable infections in healthy individuals ( Lee et al, 2017 ). Recently, carbapenem-resistant ST11 and ST15 hvKp have been reported from China, which caused an outbreak in the provincial hospital ( He et al, 2022 ; Zhao et al, 2022 ). There have also been reports of MDR-hvKps in other parts of Asia and worldwide ( Tang et al, 2020 ; Wyres et al, 2020 ; Tian et al, 2022 ).…”