Abstract
Acinetobacter pittii is a species that belong to the Acinetobacter calcoaceticus-baumannii complex, increasingly recognized as major nosocomial bacterial pathogens, often associated with multiple drug-resistances. The capsule surrounding the bacteria represents a main virulence factor, helping cells avoid phage predation and host immunity. Accordingly, a better understanding of the phage infection mechanisms is required to efficiently develop phage therapy against Acinetobacter of different capsular types. Here, we report the isolation of the novel A. pittii-infecting Fri1-like phage vB_Api_3043-K38 (3043-K38) of the Podoviridae morphotype, from sewage samples. Its 41,580 bp linear double-stranded DNA genome harbours 53 open reading frames and 302 bp of terminal repeats. We show that all studied Acinetobacter Fri1-like viruses have highly similar genomes, which differentiate only at the genes coding for tailspike, likely to adapt to different host receptors. The isolated phage 3043-K38 specifically recognizes an untapped Acinetobacter K38 capsule type via a novel tailspike with K38 depolymerase activity. The recombinant K38 depolymerase region of the tailspike (center-end region) forms a thermostable trimer, and quickly degrades capsules. When the K38 depolymerase is applied to the cells, it makes them resistant to phage predation. Interestingly, while K38 depolymerase treatments do not synergize with antibiotics, it makes bacterial cells highly susceptible to the host serum complement. In summary, we characterized a novel phage-encoded K38 depolymerase, which not only advances our understanding of phage-host interactions, but could also be further explored as a new antibacterial agent against drug-resistant Acinetobacter.
Highlights
Acinetobacter calcoaceticus-baumannii complex (ACB complex) is a leading opportunistic nosocomial pathogen
We report here the isolation and full characterization of this new tailspike protein carrying a K38-depolymerase activity, advancing our current knowledge about the mechanisms of phage interaction with bacterial strains of the ACB complex
Average nucleotide identity (ANI) values ≥ 96% strongly indicated identity at the species level [11], i.e., the genome was clearly derived from an A. pittii strain
Summary
Acinetobacter calcoaceticus-baumannii complex (ACB complex) is a leading opportunistic nosocomial pathogen. The alarming emergency of carbapenem-resistant clones, together with the lack of viable antimicrobial options, has placed A. baumannii as the leading priority pathogen since 2017 by the World Health Organization. This should be carefully interpreted, as hospital routines cannot distinguish among species of the ACB complex, often identifying A. baumannii by default. All have evolved to encode tailspikes with capsular depolymerase activities that recognize bacterial K types, allowing phages to infect the bacterium. We report here the isolation and full characterization of this new tailspike protein carrying a K38-depolymerase activity, advancing our current knowledge about the mechanisms of phage interaction with bacterial strains of the ACB complex
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