The Ability of Lytic Staphylococcal Podovirus vB_SauP_phiAGO1.3 to Coexist in Equilibrium With Its Host Facilitates the Selection of Host Mutants of Attenuated Virulence but Does Not Preclude the Phage Antistaphylococcal Activity in a Nematode Infection Model

Abstract

Phage vB_SauP_phiAGO1.3 (phiAGO1.3) is a polyvalent Staphylococcus lytic podovirus with a 17.6-kb genome (Gozdek et al., 2018). It can infect most of the Staphylococcus aureus human isolates of dominant clonal complexes. We show that a major factor contributing to the wide host range of phiAGO1.3 is a lack or sparcity of target sites for certain restriction-modification systems of types I and II in its genome. Phage phiAGO1.3 requires for adsorption β-O-GlcNAcylated cell wall teichoic acid, which is also essential for the expression of methicillin resistance. Under certain conditions an exposure of S. aureus to phiAGO1.3 can lead to the establishment of a mixed population in which the bacteria and phages remain in equilibrium over multiple generations. This is reminiscent of the so called phage carrier state enabling the co-existence of phage-resistant and phage-sensitive cells supporting a continuous growth of the bacterial and phage populations. The stable co-existence of bacteria and phage favors the emergence of phage-resistant variants of the bacterium. All phiAGO1.3-resistant cells isolated from the phage-carrier-state cultures contained a mutation inactivating the two-component regulatory system ArlRS, essential for efficient expression of numerous S. aureus virulence-associated traits. Moreover, the mutants were unaffected in their susceptibility to infection with an unrelated, polyvalent S. aureus phage of the genus Kayvirus. The ability of phiAGO1.3 to establish phage-carrier-state cultures did not preclude its antistaphylococcal activity in vivo in an S. aureus nematode infection model. Taken together our results suggest that phiAGO1.3 could be suitable for the therapeutic application in humans and animals, alone or in cocktails with Kayvirus phages. It might be especially useful in the treatment of infections with the majority of methicillin-resistant S. aureus strains.

Evaluation of Staphylococcal Bacteriophage Sb-1 as an Adjunctive Agent to Antibiotics Against Rifampin-Resistant Staphylococcus aureus Biofilms

“…Phage efficacy has been described to be influenced by host specificity, among several other factors (Ly-Chatain, 2014). In our study, Sb-1 showed high killing effect against most tested strains, but still a complete biofilm eradication with the phage alone was not achieved, possibly due to the establishment of an equilibrium between virus and host, as reported earlier (Głowacka-Rutkowska et al, 2019), what might be prevented with the addition of antibiotics.…”

Molecular Insights into Bacteriophage Evolution toward Its Host

“…This indicates that the bacteria gained some resistance to the phages, probably as a result of coevolution occurring along the experiment [ 27 , 37 ]. Another possible explanation for the relatively stable bacterial concentrations could be pseudolysogeny [ 38 , 39 , 40 ]. However, no significant morphological changes were observed in the bacterial colonies.…”

TSP, a virulent Podovirus can control the growth of Staphylococcus aureus till 12 hours

“…Based on genome length, low G+C content and gene organization, TSP phage is similar to that of wellstudied S. aureus lytic phages SLPW, VB_SauP_PhiAG01.3, P66, S13, and SCH1 [38][39][40]6] which were successfully applied for the treatment of S. aureus infections. Genes involved in structure, DNA replication, packaging and lysis showed best match with other Podoviridae phages listed in supplementary Table S3 [41].…”