Bacteriophages of Klebsiella spp., their diversity and potential therapeutic uses

Abstract

Klebsiella spp. are commensals of the human microbiota, and a leading cause of opportunistic nosocomial infections. The incidence of multidrug resistant (MDR) strains of Klebsiella pneumoniae causing serious infections is increasing, and Klebsiella oxytoca is an emerging pathogen. Alternative strategies to tackle infections caused by these bacteria are required as strains become resistant to last-resort antibiotics such as colistin. Bacteriophages (phages) are viruses that can infect and kill bacteria. They and their gene products are now being considered as alternatives or adjuncts to antimicrobial therapies. Several in vitro and in vivo studies have shown the potential for lytic phages to combat MDR K. pneumoniae infections. Ready access to cheap sequencing technologies has led to a large increase in the number of genomes available for Klebsiella-infecting phages, with these phages being heterogeneous at the whole-genome level. This review summarizes our current knowledge on phages of Klebsiella spp. and highlights technological and biological issues relevant to the development of phage-based therapies targeting these bacteria.

Keywords: Klebsiella oxytoca; Klebsiella pneumoniae; antimicrobial resistance; phage therapy.

Fig. 1.

Phylogenetic placement of dsDNA Klebsiella phages within the order Caudovirales. Placement of 109 genomes (Table 1) within ViPTree version 1.9 [164] was checked on 6 August 2019. Those sequences (n=84) that clustered together in groups of three or more were analysed with their nearest phylogenetic relatives using ViPTreeGen v1.1.2 (--ncpus 8 --method ‘bioinj’) and a non-redundant set of genomes (a fasta file of input sequences, https://doi.org/10.6084/m9.figshare.11635965.v1; newick-format file, https://doi.org/10.6084/m9.figshare.11635953.v1) to generate the tree shown (annotated using https://itol.embl.de and Adobe Illustrator). The taxonomy of the phages was checked via https://talk.ictvonline.org/taxonomy/ (release 2018b); accepted species names are written in italics. A phylogenetic tree showing the placement of the remaining 25 Klebsiella genomes within ViPTree version 1.9 is available (https://doi.org/10.6084/m9.figshare.11635962.v1; genome list, https://doi.org/10.6084/m9.figshare.11635950.v1; newick-format file, https://doi.org/10.6084/m9.figshare.11635971.v1) as Supplementary Material. Since the trees in this figure and the Supplementary Material were created, genomes for the following phages have been published: vB_KpnS_FZ10, Shelby, Sin4, Skenny, Sweeny and Sanco (Webervirus); vB_KpnP_FZ12 (Przondovirus); vB_KpnM_FZ14 (Jedunavirus); vB_KpnS_FZ41 and KpGranit (Sugarlandvirus); Patroon (Teseptimavirus); KpCHEMY26 (Ithacavirus); Magnus (genus unknown); Mulock (related to Brunovirus); Marfa (genus unknown). Additional information for these phages is available in Table 1.