gms | German Medical Science

The worldwide spread of methicillin-resistant Staphylococcus aureus (MRSA) strains has challenged the treatment of infections caused by S. aureus and emphasized the importance of preventive strategies. S. aureus carriage is a major risk factor for subsequent infection, thus, decolonization has become one of the main approaches to prevent infection and reduce transmission. Mupirocin ointment is currently a standard topical antibiotic for nasal decolonization of S. aureus, but its use has been compromised by the need for long application (5–7 days), damage to the commensal flora, bacteriostatic activity and growing resistance.

The recent increase in antibiotic resistance and lack of new innovative antibiotics revitalized interest in use of bacteriophages and bacteriophage endolysins against pathogenic bacteria. Endolysins are peptidoglycan hydrolases produced by bacteriophages to cause degradation of bacterial cell wall followed by rapid cell lysis. Endolysins have been shown to kill Gram-positive bacteria even if applied exogenously. In the recent years, several recombinantly produced bacteriophage endolysins have been investigated by academic institutions and biotech companies for use in S. aureus decolonization regimens. In vitro data have demonstrated very specific and rapid bactericidal activity of endolysins against S. aureus. Furthermore, high efficacy and safety of recombinant endolysins against S. aureus have been shown in vivo using mice nasal elimination models. Several endolysins have entered drug development programs for S. aureus decolonization and are currently in preclinical or clinical development.

The rapid activity and high specificity of bacteriophage endolysins make them promising targeted agents for S. aureus decolonization.