Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice

Qingqing Fang; Yu Feng; Alan McNally; Zhiyong Zong

doi:10.1038/s42003-022-03001-y

Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice

Qingqing Fang, Yu Feng, Alan McNally, Zhiyong Zong

Microbiology and Infection

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Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe global health challenge. We isolate and characterize two previously unidentified lytic phages, P24 and P39, with large burst sizes active against ST11 KL64, a major CRKP lineage. P24 and P39 represent species of the genera Przondovirus (Studiervirinae subfamily) and Webervirus (Drexlerviridae family), respectively. P24 and P39 together restrain CRKP growth to nearly 8 h. Phage-resistant mutants exhibit reduced capsule production and decreased virulence. Modifications in mshA and wcaJ encoding capsule polysaccharide synthesis mediate P24 resistance whilst mutations in epsJ encoding exopolysaccharide synthesis cause P39 resistance. We test P24 alone and together with P39 for decolonizing CRKP using mouse intestinal colonization models. Bacterial load shed decrease significantly in mice treated with P24 and P39. In conclusion, we report the characterization of two previously unidentified lytic phages against CRKP, revealing phage resistance mechanisms and demonstrating the potential of lytic phages for intestinal decolonization.

Original language	English
Article number	48
Number of pages	14
Journal	Communications Biology
Volume	5
Issue number	1
Early online date	13 Jan 2022
DOIs	https://doi.org/10.1038/s42003-022-03001-y
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
This work is part of the DETECTIVE project supported by the National Natural Science Foundation of China (81861138055) and the Medical Research Council (MR/S013660/1). This work was also supported by a grant from the West China Hospital of Sichuan University (grant no. ZYYC08006). We thank Weilong Zhou for his assistance with a glowing reference.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

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title = "Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice",

abstract = "Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe global health challenge. We isolate and characterize two previously unidentified lytic phages, P24 and P39, with large burst sizes active against ST11 KL64, a major CRKP lineage. P24 and P39 represent species of the genera Przondovirus (Studiervirinae subfamily) and Webervirus (Drexlerviridae family), respectively. P24 and P39 together restrain CRKP growth to nearly 8 h. Phage-resistant mutants exhibit reduced capsule production and decreased virulence. Modifications in mshA and wcaJ encoding capsule polysaccharide synthesis mediate P24 resistance whilst mutations in epsJ encoding exopolysaccharide synthesis cause P39 resistance. We test P24 alone and together with P39 for decolonizing CRKP using mouse intestinal colonization models. Bacterial load shed decrease significantly in mice treated with P24 and P39. In conclusion, we report the characterization of two previously unidentified lytic phages against CRKP, revealing phage resistance mechanisms and demonstrating the potential of lytic phages for intestinal decolonization.",

author = "Qingqing Fang and Yu Feng and Alan McNally and Zhiyong Zong",

note = "Funding Information: This work is part of the DETECTIVE project supported by the National Natural Science Foundation of China (81861138055) and the Medical Research Council (MR/S013660/1). This work was also supported by a grant from the West China Hospital of Sichuan University (grant no. ZYYC08006). We thank Weilong Zhou for his assistance with a glowing reference. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Feng, Yu

AU - McNally, Alan

AU - Zong, Zhiyong

N1 - Funding Information: This work is part of the DETECTIVE project supported by the National Natural Science Foundation of China (81861138055) and the Medical Research Council (MR/S013660/1). This work was also supported by a grant from the West China Hospital of Sichuan University (grant no. ZYYC08006). We thank Weilong Zhou for his assistance with a glowing reference. Publisher Copyright: © 2022, The Author(s).

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Y1 - 2022/12

N2 - Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe global health challenge. We isolate and characterize two previously unidentified lytic phages, P24 and P39, with large burst sizes active against ST11 KL64, a major CRKP lineage. P24 and P39 represent species of the genera Przondovirus (Studiervirinae subfamily) and Webervirus (Drexlerviridae family), respectively. P24 and P39 together restrain CRKP growth to nearly 8 h. Phage-resistant mutants exhibit reduced capsule production and decreased virulence. Modifications in mshA and wcaJ encoding capsule polysaccharide synthesis mediate P24 resistance whilst mutations in epsJ encoding exopolysaccharide synthesis cause P39 resistance. We test P24 alone and together with P39 for decolonizing CRKP using mouse intestinal colonization models. Bacterial load shed decrease significantly in mice treated with P24 and P39. In conclusion, we report the characterization of two previously unidentified lytic phages against CRKP, revealing phage resistance mechanisms and demonstrating the potential of lytic phages for intestinal decolonization.

AB - Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe global health challenge. We isolate and characterize two previously unidentified lytic phages, P24 and P39, with large burst sizes active against ST11 KL64, a major CRKP lineage. P24 and P39 represent species of the genera Przondovirus (Studiervirinae subfamily) and Webervirus (Drexlerviridae family), respectively. P24 and P39 together restrain CRKP growth to nearly 8 h. Phage-resistant mutants exhibit reduced capsule production and decreased virulence. Modifications in mshA and wcaJ encoding capsule polysaccharide synthesis mediate P24 resistance whilst mutations in epsJ encoding exopolysaccharide synthesis cause P39 resistance. We test P24 alone and together with P39 for decolonizing CRKP using mouse intestinal colonization models. Bacterial load shed decrease significantly in mice treated with P24 and P39. In conclusion, we report the characterization of two previously unidentified lytic phages against CRKP, revealing phage resistance mechanisms and demonstrating the potential of lytic phages for intestinal decolonization.

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Characterization of phage resistance and phages capable of intestinal decolonization of carbapenem-resistant Klebsiella pneumoniae in mice

Abstract

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