Abstract
The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010–2015 and discovered 18 isolates from 7 patients also harbored hypervirulence features. All isolates contained a closely related plasmid (pKPC2) harboring blaKPC-2, a K. pneumoniae carbapenemase gene, and had a hypervirulent background of capsular serotypes K1, K2, and K20. In total, 5 of 7 first patient isolates were hypermucoviscous, and 6 were virulent in mice. The pKPC2 was highly transmissible and remarkably stable, maintained in bacteria within a patient with few changes for months in the absence of antimicrobial drug selection pressure. Intrapatient isolates were also able to acquire additional antimicrobial drug resistance genes when inside human bodies. Our results highlight the potential spread of carbapenem-resistant hypervirulent K. pneumoniae in Singapore.
Highlights
The Carbapenemase-Producing Enterobacteriaceae in Singapore (CaPES) study initiated in 2013 revealed that the rate of incident carbapenem-resistant Enterobacteriaceae clinical cultures in government hospitals in Singapore increased during 2011–2013 and plateaued thereafter [8]
Discovery of Hypervirulent Features of CRKP We retrieved 1,312 carbapenem-resistant Enterobacteriaceae collected from 6 public hospitals in Singapore during 2010–2015 through the CaPES program and National Public Health Laboratory of Singapore; 1,251 isolates were whole-genome sequenced with Illumina technology, and 556 isolates were K. pneumoniae
The differences found among isolates from the same patient were small (0–15 single-nucleotide polymorphism (SNP)) (Figure 1, panel A), suggesting that patients with multiple isolates were infected with a single strain
Summary
The Carbapenemase-Producing Enterobacteriaceae in Singapore (CaPES) study initiated in 2013 revealed that the rate of incident carbapenem-resistant Enterobacteriaceae clinical cultures in government hospitals in Singapore increased during 2011–2013 and plateaued thereafter [8]. Hypervirulent K. pneumoniae and CRKP isolates can converge in the same organism, leading to the emergence of superbugs resistant to antimicrobial drugs of even the last line of treatment that are capable of infecting healthy persons. This emergence has already been reported in China, Brazil, and the United Kingdom [13,14,15]. If that hypothesis is correct, MDR clones acquiring virulence genes or K. pneumoniae virulence plasmids would be more likely than hypervirulent clones acquiring MDR genes To investigate this hypothesis, we searched for hypervirulent isolates among 556 CRKP isolates collected at public hospitals of Singapore
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