Fighting multi-drug resistant Klebsiella pneumoniae by using lytic phages

Introduction: The pandemic diffusion of KPC-producing Klebsiella pneumoniae (KPC-Kp) represents a major public health problem, given their wide spread in nosocomial environments, their extensive multidrug resistance profiles and the very high mortality rates1,2. Here we characterized two phages able to specifically lyse isolates of the pandemic clones of KPC-Kp, and demonstrated their ability in the protection towards death in a Galleria mellonella infection model. Material & Methods: Bacteriophages were isolated from hospital wastewaters. Host specificity was assessed by spot technique. Phages were characterized by TEM and WGS analysis. The ability of phages to protect towards death was assessed by using a G. mellonella infection model. Results: Phages were able to selectively lyse specific KPC-Kp lineages (i.e. CG258-clade I, CG258-clade II)3,4. One phage belonged to Myoviridae, while the other was of the Podoviridae family. Phages were able to protect towards death larvae of G. mellonella infected by representatives of the 2 CG258 clades, including one isolate with a hypermucoviscous phenotype. Conclusion: To our best knowledge these are the first characterized lytic phages targeting KPC-Kp strains of this pandemic CG that could be of potential interest to develop new agents for the treatment of KPC-Kp infections and for decolonization purposes. References: 1. Munoz-Price, L. S., et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect. Dis. 13, 785-796 (2013). 2. Lee, C. R. et al. Global dissemination of carbapenemase-producing Klebsiella pneumonia epidemiology, genetic context, treatment options, and detection methods. Front. Microbiol. 7, 895;10.3389/fmicb.2016.00895 (2016). 3. Chen, L., Mathema, B., Pitout, J. D., DeLeo, F. R. & Kreiswirth B. N. Epidemic Klebsiella pneumonia ST258 is a hybrid strain. MBio 5, e01355-14; mBio.01355-14 (2014). 4. D'Andrea, M. M. et al. Diversity of capsular polysaccharide gene clusters in KPC-producing Klebsiella pneumoniae clinical isolates of sequence type 258 involved in the Italian epidemic. PLoS One 9,96827. 10.1371/journal.pone.0096827 (2014).