Abstract

Surfaces of implanted medical devices are highly susceptible to biofilm formation. Bacteria in biofilms are embedded in a self-produced extracellular matrix that inhibits the penetration of antibiotics and significantly contributes to the mechanical stability of the colonizing community which leads to an increase in morbidity and mortality rate in clinical settings. Therefore, new antibiofilm approaches and substances are urgently needed. In this paper, we test the efficacy of a broad-range recombinant endolysin of the coliphage LysECD7 against forming and mature biofilms. We used a strong biofilm producer—Klebsiella pneumoniae Ts 141-14 clinical isolate. In vitro investigation of the antibacterial activity was performed using the standard biofilm assay in microtiter plates. We optimized the implantable diffusion chamber approach in order to reach strong biofilm formation in vivo avoiding severe consequences of the pathogen for the animals and to obtain a well-reproducible model of implant-associated infection. Endolysin LysECD7 significantly reduced the biofilm formation and was capable of degrading the preformed biofilm in vitro. The animal trials on the preformed biofilms confirmed these results. Overall, our results show that LysECD7 is a promising substance against clinically relevant biofilms.

Highlights

  • New antibacterial strategies and agents are urgently needed due to the emergence and development of resistance to conventional antibiotics

  • Multidrug-resistant Klebsiella pneumoniae strain Ts 141-14 was initially isolated from the urine of a patient, hospitalized in the Medical and Rehabilitation Center, Moscow, in 2014

  • Bacteria were grown on nutrient media GRM 1 (SRCAMB, Obolensk, Russia) and Mueller–Hinton broth and agar (Thermo Fisher Scientific, Waltham, MA, USA) at 37 ◦ C under aerobic conditions

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Summary

Introduction

New antibacterial strategies and agents are urgently needed due to the emergence and development of resistance to conventional antibiotics. Formation of bacterial biofilm (BF) is a risk factor of infectious disease development. The antibiotic response patterns in BF significantly vary from those specific for the planktonic cells [1]. The bacterial community became more tolerant to antibacterial substances and more mechanically stable [2]. Clinical treatments with antibiotics concentrations determined for planktonic bacteria may result in persistent infection formation.

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