Pharmacokinetics and Preclinical Safety Studies of Modified Endolysin-based Gel for Topical Application.

Antibacterial therapy with phage-encoded endolysins or their modified derivatives with improved antibacterial, biochemical and pharmacokinetic properties is one of the most promising strategies that can supply existing antibacterial drugs array. Gram-negative bacteria-induced infections treatment is especially challenging because of rapidly spreading bacterial resistance. We have developed modified endolysin LysECD7-SMAP with a significant antibacterial activity and broad spectra of action against gram-negative bacteria. Endolysin was formulated in a bactericidal gel for topical application with pronounced effectivity in local animal infectious models. Here we present preclinical safety studies and pharmacokinetics of LysECD7-SMAP-based gel. We have detected LysECD7-SMAP in the skin and underlying muscle at therapeutic concentrations when the gel is applied topically to intact or injured skin. Moreover, the protein does not enter the bloodstream, and has no systemic bioavailability, assuming no systemic adverse effects. In studies of general toxicology, local tolerance, and immunotoxicology it was approved that LysECD7-SMAP gel local application results in the absence of toxic effects after single and multiple administration. Thus, LysECD7-SMAP-containing gel has appropriate pharmacokinetics and can be considered as safe that supports the initiation of the phase I clinical trials of novel antibacterial drug intending to treat acute wound infections caused by resistant gram-negative bacteria.

DETECTION OF OPHIDIOMYCES OPHIDIICOLA IN THREE FILE SNAKES (ACROCHORDUS GRANULATUS) IMPORTED FROM INDONESIA TO THE MOSCOW ZOO (RUSSIA).

Three file snakes (Acrochordus granulatus) were delivered to the Moscow Zoo (Russia) from Jakarta (Indonesia). Shortly after arrival, multiple white blisters were detected on their bodies. All three snakes died within a month of arrival. On microscopy, arthrospores and mycelium were seen in exudate from the lesions. Ophidiomyces ophidiicola was isolated from two of three snakes and identified by internal transcribed spacer sequencing. Dermatophyte test medium turned red in positive cultures and can be potentially employed for detection of O. ophidiicola, the causative agent of snake fungal disease. This is the first report of O. ophidiicola in Russia and the second reported case of ophidiomycosis in file snakes. The possible source of O. ophidiicola in snakes imported from Southeast Asia is discussed.