Bioprospecting Staphylococcus Phages with Therapeutic and Bio-Control Potential

Abstract

Emergence of antibiotic-resistant bacteria is a serious threat to the public health. This is also true for Staphylococcus aureus and other staphylococci. Staphylococcus phages Stab20, Stab21, Stab22, and Stab23, were isolated in Albania. Based on genomic and phylogenetic analysis, they were classified to genus Kayvirus of the subfamily Twortvirinae. In this work, we describe the in-depth characterization of the phages that electron microscopy confirmed to be myoviruses. These phages showed tolerance to pH range of 5.4 to 9.4, to maximum UV radiation energy of 25 µJ/cm2, to temperatures up to 45 °C, and to ethanol concentrations up to 25%, and complete resistance to chloroform. The adsorption rate constants of the phages ranged between 1.0 × 10−9 mL/min and 4.7 × 10−9 mL/min, and the burst size was from 42 to 130 plaque-forming units. The phages Stab20, 21, 22, and 23, originally isolated using Staphylococcus xylosus as a host, demonstrated varied host ranges among different Staphylococcus strains suggesting that they could be included in cocktail formulations for therapeutic or bio-control purpose. Phage particle proteomes, consisting on average of ca 60–70 gene products, revealed, in addition to straight-forward structural proteins, also the presence of enzymes such DNA polymerase, helicases, recombinases, exonucleases, and RNA ligase polymer. They are likely to be injected into the bacteria along with the genomic DNA to take over the host metabolism as soon as possible after infection.

Identification and Characterization of the CRISPR/Cas System in Staphylococcus aureus Strains From Diverse Sources

“…The effort and the economic consumption to the development of antimicrobial products ( Chung and Khanum, 2017 ; Hashemi et al, 2018 ), mainly those are effective against MDR strains with metal in the form of a nanoparticle ( Alavi and Rai, 2019 ; Heidary et al, 2019 ; Kumar et al, 2019 ), have promoted the search of new treatments, particularly the treatment of bacteriophages ( Wernicki et al, 2017 ). The bacteriophages are being considered as an alternative to therapy in S. aureus MDR strains (MRSA), S. haemolyticus (MRSH), and Staphylococcus epidermidis (MRSE) infections ( Oduor et al, 2020 ). However, in this study, we found that the CRISPR-Cas system may be a factor that could compromise the efficacy of bacteriophage therapy.…”

“…(MRSA, MSSA, Staphylococcus intermedius , S. epidermidis , Staphylococcus saprophyticus , and S. haemolyticus ) strains; moreover, it was found that Stab20 and Stab21 are better spread in some S. aureus strains. The Stab21 bacteriophage is capable to infect an isolated S. aureus from a patient with chronic sinusitis ( Oduor et al, 2020 ). The presence of one SE that matches with Stab20 in the loci CRISPR of the 08BA02176 strain implies that infection with this strain would be difficult, or impossible to treat with a Stab20 bacteriophage therapy.…”

Contribution of Podoviridae and Myoviridae bacteriophages to the effectiveness of anti-staphylococcal therapeutic cocktails

“…A multicenter, randomized controlled study in a population of patients with severe clinical conditions has been conducted with a phage cocktail produced according to good manufacturing practices 17 . The successful use of a good manufacturing practice for the preparation of virulent staphylococcal bacteriophages for intravenous administration was also reported 18 .…”

Bacteriophage-Resistant Mutant of Enterococcus faecalis Is Impaired in Biofilm Formation

“…The mixtures were incubated at 37°C with shaking at 220 rpm for 60 min. And the phage titer was determined using the DLA method ( Oduor et al, 2020 ).…”