Abstract
BackgroundMultidrug-resistant Klebsiella pneumoniae spp. (kp) are emerging agents of severe infections of the respiratory, urinary tract and wounds that can progress to fatal septicemia. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy.ResultsIn this study, we report capsule (K)-typing of 163 carbapenem-resistant Kp (CRKP) isolated 2014–2018 at the Military Hospital of Instruction of Tunis (MHT), Tunisia, by partial amplification and sequencing of the Kp wzi gene. The most prevalent K-type overall was K64 with 50.3% followed by K17 and K27 (22.7 and 11.0%, respectively). K64 Kp strains were most common and associated with increased case/fatality rates, especially at the intensive care unit (ICU). Using a K64 Kp strain we isolated and characterized a lytic Kp phage, vB_KpP_TUN1 (phage TUN1), from wastewater samples of the ICU at the MHT. TUN1 belongs to the Autographiviridae family and specifically digests K64 Kp capsules most probably via a depolymerase encoded by gp47. Furthermore, we successfully assembled phage TUN1 in a non-replicative host (E. coli) raising the possibility of in vitro assembly in the absence of live bacterial hosts. We propose that phage TUN1 is a promising candidate to be used as an adjuvant or an alternative to antibiotic therapy in CRKP infections, facilitating regulatory approval of phage therapy.ConclusionsK64, K17 and K27 are the most common wzi capsule types in this geographical location in Northern Africa. The lytic phage TUN1 efficiently lyses K64 Kp strains associated with increased case/fatality rates at body temperature. Together with its ability to be rescued in a non-replicative host these features enhance the utility of this phage as an antibacterial agent.
Highlights
The spread of multidrug-resistant bacteria (MDRB) is an increasing global problem [1]
The lytic phage TUN1 efficiently lyses Capsule type 64 (K64) Klebsiella pneumoniae (Kp) strains associated with increased case/fatality rates at body temperature
We identified and characterized the lytic phage TUN1, a T7-type bacteriophage specific for Kp with the predominant capsule type K64 associated with increased case/fatality rates
Summary
The spread of multidrug-resistant bacteria (MDRB) is an increasing global problem [1]. The risk of life-threatening infections, including septicemia, grows and new therapeutic approaches are required. Bacteriophages targeting specific bacteria are considered a promising alternative to standard broad-spectrum antibiotic therapy, or an adjuvant to more specific antibiotic therapies, especially in the case of MDRB infections. The ESKAPEE group of bacterial pathogens comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli [2] highlights the clinical impact of MDRB, and illustrates the prevalence of multidrug-resistant gram-negative bacteria (MRGN) [3]. MRGN including Klebsiella pneumoniae (Kp) are a problem in the military setting, indicated by the prevalence of MRGN in role 1 to 3 military treatment facilities [4]. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy
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