Propagation of S. aureus Phage K in Presence of Human Blood
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 18, Issue 4
Abstract
Bacteriophage (phage) treatment has proven successful for the treatment of bacteremia caused by Staphylococcus aureus (SA). Surprisingly, a recent study shows that blood inhibits SA phage propagation in vitro. Here we investigate putative in vitro inhibition of SA and/or phage K propagation by human whole blood, serum and plasma. We studied the ability of phage K to produce progeny in three SA strains growing in different media. The ability of S. aureus to multiply in human whole blood, serum and plasma were determined by CFU (Colony Forming Units) titration. Phage K propagation was evaluated by PFU (Plaque Forming Units) titration using on the double agar overlay technique. S. aureus grows robustly in whole blood and serum. By contrast, whole blood, serum and plasma strongly inhibit the propagation of phage K in three different SA strains. Our results demonstrate that SA-phage propagation inhibition by blood is not due to lack of growth of the host, and suggest an effect of the liquid components of human blood preventing the propagation of phage K.The specter of antimicrobial resistance has been present as far back as antibiotic treatment for bacterial infections has been available [1]. The current state of bacterial resistance to antibiotics coupled with inadequate development of more potent drugs is increasing the proportion of untreatable bacterial infections [2,3]. Currently more than 23,000 deaths are attributed to multi-drug resistant microorganisms in the United States each year, with worldwide deaths from resistance estimated to reach 10 million by 2050 [4]. One such resistant bacteria, Methicillin Resistant Staphylococcus aureus (MRSA), is of special international concern [2]. MRSA represents a primary cause of hospital acquired infections and is responsible for over 12,000 related deaths in the United States each year [5]. Identifying efficacious novel therapies to combat the inexorable increase in MRSA commensurate is imperative to public health. Among the novel approaches to combat bacterial resistance, phages have been utilized as a standalone and adjunct of antibiotic treatment to combat antibiotic resistance [6]. Phages are prokaryotic viruses that infect and replicate within bacteria. In the case of lytic phages, the result of this infection is bacterial lysis/killing and release of phage progeny in other sites of infection in the body which continues the life cycle. Phage therapy employs targeted application of lytic phage(s) to infect and kill a specific pathogenic bacterium [7-10].Phage therapy is highly relevant for military medicine, both on the battlefield and in military treatment facilities in the United States. Phage therapy during World War II lead to significant decreases in gangrene and amputations.10 During recent conflicts almost 9% of all United States combat deaths were caused by wound exposure to bacteria in the battlefield; these infections have a high prevalence of multidrug-resistance.10 Western medicine has reembraced phage therapy due to the rapid increase in bacterial multidrug resistance at the end of the 20th century [7,9, 11-13]. Phage therapy can clear Enterococcus and Vibrio infections in mouse and rabbit models and protect against S. aureus (SA) and E. coli infections in mouse model studies [9,13-18]. Moreover, the efficacy and safety of phage therapy has also been demonstrated in humans [19-23].In the case of MRSA-mediated septicemia, therapy with phage S13′ has proven effective in mice [24]. These results are important given over half a million cases of sepsis occur each year in the United States, resulting in up to 50 percent mortality despite antibiotic treatment [25].
Authors and Affiliations
Kenneth Frati, Francisco Malagon, Matthew Henry, Elih Velazquez Delgado, Theron Hamilton, Michael G Stockelman, Christopher Duplessis, Biswajit Biswas
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