Clonal transmission of polymyxin B-resistant hypervirulent Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaKPC-2 in a tertiary hospital in China

Abstract

Background The prevalence of multidrug-resistant hypervirulent K. pneumoniae (MDR-hvKP) has gradually increased. It poses a severe threat to human health. However, polymyxin-resistant hvKP is rare. Here, we collected eight polymyxin B-resistant K. pneumoniae isolates from a Chinese teaching hospital as a suspected outbreak. Results The minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. HvKP was identified by detecting virulence-related genes and using a Galleria mellonella infection model. Their resistance to serum, growth, biofilm formation, and plasmid conjugation were analyzed in this study. Molecular characteristics were analyzed using whole-genome sequencing (WGS) and mutations of chromosome-mediated two-component systems pmrAB and phoPQ, and the negative phoPQ regulator mgrB to cause polymyxin B (PB) resistance were screened. All isolates were resistant to polymyxin B and sensitive to tigecycline; four were resistant to ceftazidime/avibactam. Except for KP16 (a newly discovered ST5254), all were of the K64 capsular serotype and belonged to ST11. Four strains co-harbored blaKPC-2, blaNDM-1, and the virulence-related genes prmpA, prmpA2, iucA, and peg344, and were confirmed to be hypervirulent by the G. mellonella infection model. According to WGS analysis, three hvKP strains showed evidence of clonal transmission (8–20 single nucleotide polymorphisms) and had a highly transferable pKOX_NDM1-like plasmid. KP25 had multiple plasmids carrying blaKPC-2, blaNDM-1, blaSHV-12, blaLAP-2, tet(A), fosA5, and a pLVPK-like virulence plasmid. Tn1722 and multiple additional insert sequence-mediated transpositions were observed. Mutations in chromosomal genes phoQ and pmrB, and insertion mutations in mgrB were major causes of PB resistance. Conclusions Polymyxin-resistant hvKP has become an essential new superbug prevalent in China, posing a serious challenge to public health. Its epidemic transmission characteristics and mechanisms of resistance and virulence deserve attention.

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae

“…In 2021, Huang et al reported that a KPC-2-producing K. pneumoniae strain acquired a bla NDM-5 -harbouring plasmid during ceftazidime/avibactam treatment. 29 The emergence of CRKP coharboring bla KPC-3 and bla NDM-1 , 30 CRKP coharboring bla KPC-2 and bla NDM-6 , 31 hypervirulent CRKP coharboring bla KPC-2 and bla NDM-1 , 32 tigecyclineresistant hypervirulent K. pneumoniae cocarrying bla KPC-2 and bla NDM-5 , 33 polymyxin B-resistant hypervirulent K. pneumoniae coharboring bla KPC-2 and bla NDM-1 , 34 and CRKP coharboring bla KPC-2 , bla NDM-1 , and tmexCD1-toprJ1 have been successively reported. 35 The proportion of KPC-NDM-CRKP isolates was 10.8%, which was 30 times higher than that reported in the previous study.…”

Hypervirulent Klebsiella pneumoniae

“…In a similar mechanism, mutations in pmrB and phoQ genes and insertion mutations in mgrB could result in polymyxin B-resistant hvKP. 46 …”

Klebsiella pneumoniae ST147 harboring bla NDM-1 , multidrug resistance and hypervirulence plasmids

“…Over 78 capsular serotypes of K. pneumoniae have been reported; K1 and K2 serotypes are the most prevalent in hv-KP ( 16 – 19 ). Most hv-KP strains are susceptible to the commonly prescribed antibiotics, including carbapenems ( 20 ). However, these strains can acquire carbapenem or multidrug resistance that can lead to the emergence of isolates that have combined resistance and virulence.…”