Hypervirulent Klebsiella pneumoniae (hvKP) has spread globally since first described in the Asian Pacific Rim. It is an invasive variant that differs from the classical K. pneumoniae (cKP), with hypermucoviscosity and hypervirulence, causing community-acquired infections, including pyogenic liver abscess, pneumonia, meningitis, and endophthalmitis. It utilizes a battery of virulence factors for survival and pathogenesis, such as capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, and type 6 secretion system, of which the former two are dominant. This review summarizes these hvKP-associated virulence factors in order to understand its molecular pathogenesis and shed light on new strategies to improve the prevention, diagnosis, and treatment of hvKP-causing infection.

Here we completely sequenced four mcr-1 -haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1 -harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST25 isolates were identical (all pMCR1-IncX4), belonging to the IncX4 incompatibility group, while the plasmid from an E. coli ST2085 isolate (pMCR1-IncI2) belongs to the IncI2 group. A nearly identical 2.6-kb mcr-1-pap2 element was found to be shared by all mcr-1 -carrying plasmids.

Carbapenem-resistant Enterobacteriaceae (CRE) have spread rapidly around the world in the past few years, posing great challenges to human health. The plasmid-mediated horizontal transmission of carbapenem-resistance genes is the main cause of the surge in the prevalence of CRE. Therefore, the timely and accurate detection of CRE, especially carbapenemase-producing Enterobacteriaceae, is very important for the clinical prevention and treatment of these infections. A variety of methods for the rapid detection of CRE phenotypes and genotypes have been developed for use in clinical microbiology laboratories. To overcome the lack of efficient antibiotics, CRE infections are often treated with combination therapies. Moreover, novel drugs and emerging strategies appeared successively and in various stages of development. In this article, we summarized the global distribution of various carbapenemases. And we focused on summarizing and comparing the advantages and limitations of the detection methods and the therapeutic strategies of CRE primarily.

The spread of the plasmid-mediated colistin resistance gene, mcr-1 , into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1 -harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1 -harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E. coli strain.

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing globally, with different molecular mechanisms described. Here we studied the molecular mechanisms of carbapenem resistance, including clonal and plasmid dissemination, of 67 CRE isolates collected between 2012 and 2016 from a tertiary hospital in Eastern China, an CRE endemic region. Species identification and susceptibility testing were performed using the BD Phoenix Automated Microbiology System. Isolates were characterized by PCR (for carbapenemases, ESBLs, AmpC and porin genes), multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and conjugation transfer experiments. Selected bla_KPC-2 -harboring plasmids were subjected to next-generation sequencing using the Illumina Miseq platform. Among the 67 CRE isolates, 42 Klebsiella pneumoniae, 10 Serratia marcescens, 6 Enterobacter cloacae, 2 Raoultella ornithinolytica, 2 K. oxytoca, 1 K. aerogenes, and 4 Escherichia coli isolates were identified. Six different carbapenemases were detected, including bla_KPC-2 (n = 45), bla_KPC-3 (n = 1), bla_NDM-1 (n = 6), bla_NDM-5 (n = 1), bla_IMP-4 (n = 2), and bla_VIM-1 (n = 2); bla_OXA-48-like genes were not detected. One E. cloacae strain possessed both bla_NDM-1 and bla_KPC-3, while two E. cloacae isolates harbored bla_NDM-1 and bla_VIM-1. ESBLs (CTX-M, SHV, and TEM) and/or AmpC (CMY, DHA, and ACT/MIR) genes were also identified in 59 isolates, including 13 strains that lacked carbapenemases. Several insertions or stop codon mutations were found within porin genes of K. pneumoniae, E. coli and S. marcescens isolates, both with and without carbapenemases. The 42 K. pneumoniae isolates belonged to 12 different sequence types (ST), with ST11 being the most common, while the 6 E. cloacae isolates comprised 4 different STs. The 10 S. marcescens all shared the same PFGE pulsotype, suggestive of clonal spread. Complete plasmid sequencing and PCR screening revealed both intra-strain and inter-species spread of a common bla_KPC-2-harboring plasmid in our hospital. Taken together, our study revealed extensive genetic diversity among CRE isolates form a single Chinese hospital. CRE isolates circulating in the hospital differ significantly in their species, STs, porin genes, carbapenemase genes, and their plasmid content, highlighting the complex dissemination of CRE in this endemic region.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant clinical problem given the limited effective antibiotics. Alternative anti-bacterial agents, such as bacteriophages, can be used as a variety of valuable tool to treat the infections caused by these antibiotic-resistant bacteria. In this study, we isolated 54 phages from medical and domestic sewage wastewater between July and September 2019, and determined their host ranges against 54 clinical CRKP isolates collected from a tertiary hospital in Eastern China. These 54 CRKP isolates were from 7 sequence types (STs) and belonged to 9 capsular K locus types (KLs), harboring blaKPC-2 (n=49), blaNDM-1 (n=5), and blaIMP-4 (n=3). Among them, the epidemic KPC-2-producing ST11 strains were most predominant (88.9 %). The 54 phages showed different host ranges from 7 to 52 CRKP isolates, and lysis ability against some CRKP ST11 strains. The total host ranges of three phages can potentially cover all 54 CRKP isolates. Among the 54 phages, phage P545, classified as a member of Myoviridaes, order Caudovirales, had a relative wide host range (96.3%), a short latent period of 20 min, and a medium burst size of 82 PFU/cell and was stably maintained at different pH values (4-10) and temperatures (up to 60 oC). P545 showed the ability to inhibit biofilm formation and to degrade the formed mature biofilms. Taken together, our study showed the newly isolated phage P545 had relative wide host range, excellent properties and antibacterial activity as well as antibiofilm activity against clinical CRKP isolates, especially the epidemic CRKP ST11 strains, providing promising candidates for future phage therapy applications.