Antimicrobial Resistance and Pathogenicity Determination of Community-Acquired Hypervirulent Klebsiella pneumoniae
Qianqian Gao1,2, Zhen Shen1, Juanxiu Qin1
1Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Abstract:
Hypervirulent Klebsiella pneumoniae (hvKp) can cause severe invasive infections in healthy and immunocompromised individuals. However, there is still lack of a consensus definition of hvKp. In this study, we solely focused on the clinical isolates cultured from subcutaneous drainage of community-acquired liver abscess cases, and an hvKp strain was defined on the basis of co-harboring virulence gene regulator of mucoid phenotype A (rmpA)/rmpA2, iucA, iroB, and peg-344. A total of 47 nonrepetitive hvKp isolates were collected from January 2015 to December 2017 in a tertiary teaching hospital in Shanghai, China. All isolates were susceptible to the commonly used antibiotics. Only one strain (RJ-Kp24) had the positive detection of blaCTX-M-14 and was resistant to ceftazidime, cefotaxime, and cefepime. S1-pulsed-field gel electrophoresis (PFGE) and southern hybridization confirmed the presence of a roughly 90 kb blaCTX-M-14-carrying plasmid and a roughly 240 kb virulence plasmid. Further analysis revealed that ST23 (n = 17) sequence type and K1 (n = 20) and K2 (n = 9) serotypes were dominant in hvKp, while only 31.9% (15/47) and 46.8% (22/47) of hvKp isolates displayed hypermucoviscosity and resistance to serum killing, respectively. For further evaluation of the pathogenicity of hvKp, six representative strains were randomly selected. Three strains, RJ-Kp10, RJ-Kp28, and RJ-Kp31, displayed a remarkable resistance to serum killing and neutrophil phagocytosis. Mouse lethality assay revealed that these strains had the 50% lethal dose (LD50) of 102-103 cell forming unit (CFU), while others had the LD50 of 104-105 CFU. These results demonstrated that strain virulence differed significantly within these defined hvKp. The convergence of multidrug resistance and enhanced virulence in K. pneumoniae has presented a major infection control challenge.
Insights
Hypervirulent Klebsiella pneumoniae (hvKp) strains causing liver abscesses were defined by specific virulence genes. Virulence varied significantly among these hvKp isolates, posing infection control challenges.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Hypervirulent Klebsiella pneumoniae (hvKp) causes severe invasive infections.
- A consensus definition for hvKp is lacking.
- This study focuses on clinical isolates from community-acquired liver abscesses.
Purpose of the Study:
- To define hvKp based on co-harboring virulence genes (rmpA/rmpA2, iucA, iroB, peg-344).
- To characterize the virulence and antibiotic susceptibility of these hvKp isolates.
- To evaluate the pathogenicity of selected hvKp strains in a mouse model.
Main Methods:
- Clinical isolates of hvKp were collected from liver abscesses.
- Virulence genes, serotypes (K1, K2), and sequence types (ST23) were analyzed.
- Antibiotic susceptibility, hypermucoviscosity, serum resistance, neutrophil phagocytosis, and mouse lethality (LD50) were assessed.
Main Results:
- 47 nonrepetitive hvKp isolates were identified.
- ST23 and K1/K2 serotypes were dominant.
- Most isolates were susceptible to common antibiotics, with one strain showing resistance to extended-spectrum cephalosporins due to blaCTX-M-14.
- Significant variation in virulence was observed, with some strains exhibiting high resistance to serum killing and neutrophil phagocytosis, and low LD50 values in mice.
Conclusions:
- A clear definition of hvKp based on specific virulence genes was established for liver abscess isolates.
- Significant differences in virulence exist among hvKp strains, impacting pathogenicity.
- The combination of multidrug resistance and enhanced virulence in K. pneumoniae presents a significant challenge for infection control.
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