Abstract
The global increase in multidrug-resistant (MDR) pathogenic bacteria has led to growing interest in bacteriophage (“phage”) therapy. Therapeutic phages are usually selected based on their ability to infect and lyse target bacteria, using in vitro assays. In these assays, phage infection is determined using target bacteria grown in standard commercial rich media, while evaluation of the actual therapeutic activity requires the presence of human blood. In the present work, we characterized the ability of two different Yersinia pestis lytic phages (ϕA1122 and PST) to infect and kill a luminescent Y. pestis EV76 strain suspended in Brain Heart Infusion (BHI)-rich medium or in human whole blood, simulating the host environment. We found that the ability of the phages to infect and lyse blood-suspended Y. pestis was not correlated with their ability to infect and lyse BHI-suspended bacteria. While the two different phages exhibited efficient infective capacity in a BHI-suspended culture, only the PST phage showed efficient lysis ability against blood-suspended bacteria. Therefore, we recommend that for personalized phage therapy, selection of phage(s) for efficient treatment of patients suffering from MDR bacterial infections should include prior testing of the candidate phage(s) for their lysis ability in the presence of human blood.
Highlights
Pandemics, either viral-derived, such as the recently emerged COVID-19, or bacterialderived, such as reemerging plague, are of major public health concern
Y. pestis infection, similar to other bacterial infections, can develop into a systemic disease [25], and as such, for the treatment of antibiotic-resistant bacteria, it is crucial to select a therapeutic phage that is able to lyse the pathogen while it is circulating in the blood or exists in “bloody” tissues
Bacterial colonies were suspended in PBS and inoculated (1:10; vol:vol) in Brain Heart Infusion (BHI) broth or in human whole blood and transferred (90 μL/well) into a 96-well transparent-bottom white microplate (Thermo Scientific Nunc: cat. no. 165306)
Summary
Either viral-derived, such as the recently emerged COVID-19, or bacterialderived, such as reemerging plague, are of major public health concern. Bacteriophages (phages) are environmentally abundant viruses that invade and replicate inside host bacteria, forming novel progenitor virions that lyse the bacteria from within and enable the spread of the viruses for the infection cycle Since their independent discovery by Frederik Twort (in 1915) and Felix d’Herelle (in 1917) [6], isolated phages have been used for the treatment of various infectious diseases, including dysentery, cholera and plague [6,7,8]. Y. pestis infection, similar to other bacterial infections, can develop into a systemic disease [25], and as such, for the treatment of antibiotic-resistant bacteria, it is crucial to select a therapeutic phage that is able to lyse the pathogen while it is circulating in the blood or exists in “bloody” tissues (such as the spleen and liver). We assessed here the ability of two different Y. pestis-lysing phages, φA1122 and PST, to infect and kill their host bacteria in the presence of human blood
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