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

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.

Emergence of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Co-harbouring a blaNDM-1-carrying Virulent Plasmid and a blaKPC-2-carrying Plasmid in an Egyptian Hospital

“…EBSI036 was determined as KL47 capsular serotype by using Kaptive software (https://github.com/katholt/Kaptive). The serotype K47 was the most reported type among CRKP infections in Asia (10)(11)(12). The virulence level of EBSI036 was confirmed using the Galleria mellonella larvae model as previously described ( Figure S1) (10,13).…”

Genomic Profiling Reveals Distinct Routes To Complement Resistance in Klebsiella pneumoniae

“…More direct information comes from recent studies using phage-derived capsule depolymerases, where K. pneumoniae strains are stripped of capsule prior to treatment with serum. In this way, at least eight different capsular types of K. pneumoniae have been confirmed to protect from serum to date, including type K1 (of NTUH-K2044) (60)(61)(62)(63)(64)(65). The magnitude of the change in serum sensitivity following enzymatic capsule removal varies depending on both the strain and the capsule type.…”

Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter Baumannii

“…To the best of our knowledge, this was the first report showing that complete bacterial eradication could be achieved with depolymerase and serum (at 50% volume ratio) treatment. In previous studies [15,21,31,35,36,46], a 50% serum (complement) ratio could only kill 2−5 log of the depolymerase treated bacteria and no further killing was noted when the serum (complement) ratio increased to 75%. Liu et al postulated the incomplete bacteria killing was due to the emergence of the resistant phenotypes [31].…”