TY - JOUR
T1 - Bacteriophage ISP eliminates Staphylococcus aureus in planktonic phase, but not in the various stages of the biofilm cycle
AU - Verheul, Mariëlle
AU - Mulder, Aat A.
AU - van Dun, Sven C.J.
AU - Merabishvili, Maia
AU - Nelissen, Rob G.H.H.
AU - de Boer, Mark G.J.
AU - Pijls, Bart G.
AU - Nibbering, Peter H.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Metal-implant associated bacterial infections are a major clinical problem due to antibiotic treatment failure. As an alternative, we determined the effects of bacteriophage ISP on clinical isolates of Staphylococcus aureus in various stages of its life cycle in relation to biofilm formation and maturation. ISP effectively eliminated all planktonic phase bacteria, whereas its efficacy was reduced against bacteria attached to the metal implant and bacteria embedded within biofilms. The biofilm architecture hampered the bactericidal effects of ISP, as mechanical disruption of biofilms improved the efficacy of ISP against the bacteria. Phages penetrated the biofilm and interacted with the bacteria throughout the biofilm. However, most of the biofilm-embedded bacteria were phage-tolerant. In agreement, bacteria dispersed from mature biofilms of all clinical isolates, except for LUH15394, tolerated the lytic activity of ISP. Lastly, persisters within mature biofilms tolerated ISP and proliferated in its presence. Based on these findings, we conclude that ISP eliminates planktonic phase Staphylococcus aureus while its efficacy is limited against bacteria attached to the metal implant, embedded within (persister-enriched) biofilms, and dispersed from biofilms.
AB - Metal-implant associated bacterial infections are a major clinical problem due to antibiotic treatment failure. As an alternative, we determined the effects of bacteriophage ISP on clinical isolates of Staphylococcus aureus in various stages of its life cycle in relation to biofilm formation and maturation. ISP effectively eliminated all planktonic phase bacteria, whereas its efficacy was reduced against bacteria attached to the metal implant and bacteria embedded within biofilms. The biofilm architecture hampered the bactericidal effects of ISP, as mechanical disruption of biofilms improved the efficacy of ISP against the bacteria. Phages penetrated the biofilm and interacted with the bacteria throughout the biofilm. However, most of the biofilm-embedded bacteria were phage-tolerant. In agreement, bacteria dispersed from mature biofilms of all clinical isolates, except for LUH15394, tolerated the lytic activity of ISP. Lastly, persisters within mature biofilms tolerated ISP and proliferated in its presence. Based on these findings, we conclude that ISP eliminates planktonic phase Staphylococcus aureus while its efficacy is limited against bacteria attached to the metal implant, embedded within (persister-enriched) biofilms, and dispersed from biofilms.
UR - http://www.scopus.com/inward/record.url?scp=85196537895&partnerID=8YFLogxK
U2 - 10.1038/s41598-024-65143-9
DO - 10.1038/s41598-024-65143-9
M3 - Article
C2 - 38909125
AN - SCOPUS:85196537895
SN - 2045-2322
VL - 14
JO - Springer Scientific Reports
JF - Springer Scientific Reports
IS - 1
M1 - 14374
ER -