Phage-derived endolysin prevents dissemination of methicillin resistant Staphylococcus aureus during oral co-infection with Candida albicans.

The oral cavity is colonized by many species of bacteria and fungi without causing serious infections of hosts. However, upon loss of homeostasis, some of these colonizers have the potential to invade the host and cause life-threatening infections. The fungus Candida albicans and the gram-positive bacterium Staphylococcus aureus represent well-studied examples. In immunocompromised mice, oral co-colonization with these two species can result in dissemination of S. aureus through the body, causing S. aureus bacteremia and subsequent sepsis. In the proof-of-principle experiments described here, we show effective prevention of dissemination of methicillin-resistant S. aureus (MRSA) using an innovative endolysin-derived chimeric protein, XZ.700. Using the established murine model for oral co-colonization, we evaluated the effect of treatment with XZ.700 in drinking water (ad libitum) and applied as a gel formulation twice a day. XZ.700 did not show any adverse reaction in the mice treated and did not show a reduction of C. albicans colonization. XZ.700 in drinking water completely prevented detectable dissemination of MRSA in co-infected mice and significantly reduced weight loss. The gel formulation showed a trend in decreased MRSA colonization of the tongue and dissemination to the kidneys, although this was not significantly different from the placebo control. Taken together, the results presented here indicate that selective removal of MRSA from the oral cavity of mice with XZ.700 during co-infection with C. albicans is effective in preventing dissemination. Further studies need to show clinical applicability of XZ.700 and related compounds in prevention of sepsis in at-risk patients.