Antibacterial Effects of Phage Lysin LysGH15 on Planktonic Cells and Biofilms of Diverse Staphylococci

Abstract

Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we observed the ability of the phage lysin LysGH15 to eliminate staphylococcal planktonic cells and biofilms formed by <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, <i>Staphylococcus haemolyticus</i>, and <i>Staphylococcus hominis</i> All these strains were sensitive to LysGH15, showing reductions in bacterial counts of approximately 4 log units within 30 min after treatment with 20 μg/ml of LysGH15, and the MICs ranged from 8 μg/ml to 32 μg/ml. LysGH15 efficiently prevented biofilm formation by the four staphylococcal species at a dose of 50 μg/ml. At a higher dose (100 μg/ml), LysGH15 also showed notable disrupting activity against 24-h and 72-h biofilms formed by <i>S. aureus</i> and coagulase-negative species. In the <i>in vivo</i> experiments, a single intraperitoneal injection of LysGH15 (20 μg/mouse) administered 1 h after the injection of <i>S. epidermidis</i> at double the minimum lethal dose was sufficient to protect the mice. The <i>S. epidermidis</i> cell counts were 4 log units lower in the blood and 3 log units lower in the organs of mice 24 h after treatment with LysGH15 than in the untreated control mice. LysGH15 reduced cytokine levels in the blood and improved pathological changes in the organs. The broad antistaphylococcal activity exerted by LysGH15 on planktonic cells and biofilms makes LysGH15 a valuable treatment option for biofilm-related or non-biofilm-related staphylococcal infections.<b>IMPORTANCE</b> Most staphylococcal species are major causes of health care- and community-associated infections. In particular, <i>Staphylococcus aureus</i> is a common and dangerous pathogen, and <i>Staphylococcus epidermidis</i> is a ubiquitous skin commensal and opportunistic pathogen. Treatment of infections caused by staphylococci has become more difficult because of the emergence of multidrug-resistant strains as well as biofilm formation. In this study, we found that all tested <i>S. aureus</i>, <i>S. epidermidis</i>, <i>Staphylococcus haemolyticus</i>, and <i>Staphylococcus hominis</i> strains were sensitive to the phage lysin LysGH15 (MICs ranging from 8 to 32 μg/ml). More importantly, LysGH15 not only prevented biofilm formation by these staphylococci but also disrupted 24-h and 72-h biofilms. Furthermore, the <i>in vivo</i> efficacy of LysGH15 was demonstrated in a mouse model of <i>S. epidermidis</i> bacteremia. Thus, LysGH15 exhibits therapeutic potential for treating biofilm-related or non-biofilm-related infections caused by diverse staphylococci.