A new bacteriophage infecting Staphylococcus epidermidis with potential for removing biofilms by combination with chimeric lysin CHAPSH3b and vancomycin.

Abstract

Staphylococcus epidermidis is the cause of serious skin and prosthetic joint infections despite being a common inhabitant of human body surfaces. However, both the rise in antibiotic resistance in this species and its ability to form biofilms are increasingly limiting the available therapeutic options against these illnesses. In this landscape, phage therapy stands out as an interesting alternative to antibiotics. In the present study, we report the isolation and characterization of a novel virulent phage infecting S. epidermidis (Staphylococcus phage IPLA-AICAT), which belongs to the Herelleviridae family. The estimated genome size of this virus is 139,941 bp, and sequence analysis demonstrated the absence of antibiotic resistance genes and virulence factors. This phage infects a high proportion (79%) of clinically relevant S. epidermidis strains and exhibits antibiofilm activity. Moreover, a combination of this phage with other antimicrobials, i.e., vancomycin and the lytic protein CHAPSH3b, further improved the reduction in surface-attached bacteria. Notably, the combination of Staphylococcus phage IPLA-AICAT (10⁹ PFU/mL) and CHAPSH3b (8 µM), originally designed to target Staphylococcus aureus, was able to reduce the number of viable cells by 3.06 log units in 5-h-old biofilms. In 24-h-old biofilms, the reduction was also significant after 6 h of treatment (2.06 log units) and 24 h of treatment (2.52 log units). These results confirm our previous data regarding the potential of phage-lysin mixtures against staphylococcal biofilms.IMPORTANCEStaphylococcus epidermidis is one of the main causes to device-associated infections mostly due to its ability to form stable biofilms attached to human tissues. Besides the inherent antimicrobial tolerance of biofilms, this microorganism is also increasingly becoming resistant to standard-of-care antibiotics. To fight against this problem, phage therapy is a viable option to complement the available antibiotics in the treatment of recalcitrant infections. This work describes a new phage infecting S. epidermidis clinical strains that is a member of the Herelleviridae family and the combination with other antimicrobials to further improve the reduction of biofilms. Together with the significant progress achieved in the development of diagnostic tools, phages and their derived proteins will bring us much closer to a therapeutic landscape in which we are not so heavily reliant on antibiotics to combat bacterial pathogens.