Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

Abstract

In this article we compare the efficacy of different pharmacological agents (ranitidine, and omeprazole) to support phage transit from stomach to distal portions of the gastrointestinal tract in rats. We show that a temporal modification of environment in the animal stomach may protect Twort-like therapeutic antistaphylococcal phage A5/80 (from bacteriophage collection of the Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland) from the inactivation by gastric juice effectively enough to enable a significant fraction of orally administered A5/80 to pass to the intestine. Interestingly, we found that yogurt may be a relatively strong in enhancing phage transit. Given the immunomodulating activities of phages our data may suggest that phages and yogurt can act synergistically in mediating their probiotic activities and enhancing the effectiveness of oral phage therapy. We also demonstrate that orally applied phages of similar size, morphology, and sensitivity to acidic environment may differ in their translocation into the bloodstream. This was evident in mice in which a therapeutic staphylococcal phage A5/80 reached the blood upon oral administration combined with antacid agent whilst T4 phage was not detected even when applied in 103 times higher dose. Our findings also suggest that phage penetration from digestive tract to the blood may be species-specific.

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“…The use of a different phage type can then in a second instance provide a solution. Moreover, phages can be inactivated for instance by leukocytes and other nonspecific blood factors, as well as by gastric juices and by antiseptics . Therefore, the use of alkalinizing agents such as sodium bicarbonates is introduced as pre‐phage application Phages also can mutate, encode toxin genes and lysogenize bacteria.…”

“…195 Therefore, the use of alkalinizing agents such as sodium bicarbonates is introduced as pre-phage application. 196 • Phages also can mutate, encode toxin genes and lysogenize bacteria. Also, their behavior under strictly anaerobic conditions (i.e.…”

A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

“…Bacteriophage MSA6, a representative member of Kayvirus genus phages and a source of tgl gene, was described previously [6,54]. MSA6 DNA was isolated from lysates of infected S. aureus RN4220 cells following the previously described procedures [6,12].…”

“…They are obligatorily lytic, and infect a broad spectrum of S. aureus strains [6,7]. Several Kayvirus genus representatives have been successfully used in experimental antistaphylococcal therapies in humans and animals [2,[8][9][10][11][12][13][14]. The genomic sequences of most of them have been determined [6,15].…”

A <em>Kayvirus</em> Distant Homolog of Staphylococcal Virulence Determinats and VISA Biomarker is a Phage Lytic Enzyme That Decreases <em>S. aureus</em> Tolerance to Vancomycin

“…They are obligatorily lytic, and infect a broad spectrum of S. aureus strains [6,7]. Several Kayvirus genus representatives have been successfully used in experimental antistaphylococcal therapies in humans and animals [2,8,9,10,11,12,13,14]. The genomic sequences of most of them have been determined [6,15].…”