Lytic bacteriophages against multidrug-resistant Staphylococcus aureus, Enterococcus faecalis and Escherichia coli strains isolated from orthopedic implant-associated infections

Abstract

Orthopedic implant-associated infections are a devastating complication with significant impact on patients and on healthcare systems. The aims of this work were to describe the patterns of antibiotic resistance, pathogenicity and virulence of clinical bacterial strains isolated from orthopedic implant-associated infections and to further isolate and characterize bacteriophages that are efficient in controlling these isolated bacteria. Staphylococcus aureus, Enterococcus faecalis and Escherichia coli, isolated from orthopedic infections, had shown multi-resistant patterns to the most frequently used antibiotics in clinical settings. The presence of mobile genetic elements (mecA, Tn916/Tn1546 and intl1) and virulence determinants (icaB, cna, hlb, cylLs, cylM, agg, gelE, fsr and fimA) emphasized the pathogenicity of these strains. Moreover, the isolates belonged to clonal complexes associated with the acquisition of pathogenicity islands and antimicrobial resistance genes by recombination and horizontal gene transfer. The bacteriophages, vB_SauM_LM12, vB_EfaS_LM99 and vB_EcoM_JB75, were characterized and their ability to infect clinical isolates of S. aureus, E. faecalis and E. coli, respectively, was assessed. Morphological and genomic analyses revealed that vB_EfaS_LM99 and vB_EcoM_JB75 belong to the Siphoviridae and Myoviridae families, respectively, and no genes associated to lysogeny were found. The bacteriophages showed low latent periods, high burst sizes, broad host ranges and tolerance to several environmental conditions. Moreover, they showed a high efficiency and specificity to infect and reduce clinical bacteria, including methicillin-resistant S. aureus and vancomycin resistant enterococci strains. Therefore, the obtained results suggest that the bacteriophages used in this work are a promising approach to control these pathogens involved in orthopedic implant-associated infections.