Identification of Two Depolymerases From Phage IME205 and Their Antivirulent Functions on K47 Capsule of Klebsiella pneumoniae.

Yannan Liu,Jichao Chen,Ning Jiang,Puyuan Li,Zhiqiang Mi,Yatao Guo,Rentao Wang,Zhancheng Gao,Sharon Shui Yee Leung,Changqing Bai,Yong Huang

doi:10.3389/fmicb.2020.00218

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a significant threat to global public health. In present research, a total of 80 CRKP strains belonging to ST11 were collected with 70% (56 of 80 isolates) expressing a K47 capsular type. Thus, it is significant to prevent and control infections caused by these bacteria. Capsule depolymerases could degrade bacterial surface polysaccharides to reduce their virulence and expose bacteria to host immune attack. Previous studies have demonstrated the potential of phage-encoded depolymerases as antivirulent agents in treating CRKP infections in vitro and in vivo. Here, two capsule depolymerases (Dpo42 and Dpo43) derived from phage IME205 were expressed and characterized. Although both depolymerases act on strains with a capsular serotype K47, they are active against different subsets of strains, indicating subtle differences in capsule composition that exist within this serotype. The host range of phage IME205 matched to the sum of specificity range of Dpo42 and Dpo43. These two enzymes maintained stable activity in a relatively broad range of pH levels (pH 5.0–8.0 for Dpo42 and pH 4.0–8.0 for Dpo43) and temperatures (20–70°C). Besides, both Dpo42 and Dpo43 could make host bacteria fully susceptible to the killing effect of serum complement and display no hemolytic activity to erythrocytes. In summary, capsule depolymerases are promising antivirulent agents to combat CRKP infections.

Highlights

Klebsiella pneumoniae is an opportunistic pathogen causing numerous hospital-acquired infections in immunocompromised individuals, including ventilator-associated pneumonia, catheter-related infection, urinary tract infection, soft tissue infection, surgical site infection and bacteremia (Paczosa and Mecsas, 2016)
The susceptibility rates of these bacteria toward different classes of antibiotics are given in Supplementary Table S1
All strains belonged to ST11 and corresponded to four capsular types (Table 1), including K16 (1.25%, 1/80), K37 (2.50%, 2/80), K47 (70.00%, 56/80), and K64 (26.25%, 21/80)

Summary

Introduction

Klebsiella pneumoniae is an opportunistic pathogen causing numerous hospital-acquired infections in immunocompromised individuals, including ventilator-associated pneumonia, catheter-related infection, urinary tract infection, soft tissue infection, surgical site infection and bacteremia (Paczosa and Mecsas, 2016). With misuse and overuse of antibiotics, infections caused by multidrugresistant (MDR) K. pneumoniae strains become an increasingly serious global problem. Among MDR isolates, carbapenemresistant K. pneumoniae (CRKP) are of particular concern due to their extended antibiotic resistance phenotypes and ability to rapidly disseminate. As few available antibiotics can be used to treat CRKP infections, these strains are associated with high mortality. There is an urgent need to seek alternatives to conventional antibiotics against severe CRKP infections

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