Abstract
Following the emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP), phage therapy has attracted significant attention as an alternative to antibiotic treatment. Bacteriophages belonging to kayvirus (previously known as Twort-like phages) have broad host range and are strictly lytic in Staphylococcus spp. Previous work revealed that kayvirus ɸSA039 has a host-recognition mechanism distinct from those of other known kayviruses: most of kayviruses use the backbone of wall teichoic acid (WTA) as their receptor; by contrast, ɸSA039 uses the β-N-acetylglucosamine (β-GlcNAc) residue in WTA. In this study, we found that ɸSA039 could switch its receptor to be able to infect S. aureus lacking the β-GlcNAc residue by acquiring a spontaneous mutation in open reading frame (ORF) 100 and ORF102. Moreover, ɸSA039 could infect S. pseudintermedius, which has a different WTA structure than S. aureus. By comparison, with newly isolated S. pseudintermedius-specific phage (SP phages), we determined that glycosylation in WTA of S. pseudintermedius is essential for adsorption of SP phages, but not ɸSA039. Finally, we describe a novel strategy of S. aureus which protects the bacteria from infection of SP phages. Notably, glycosylation of ribitol phosphate (RboP) WTA by TarM or/and TarS prevents infection of S. aureus by SP phages. These findings could help to establish a new strategy for the treatment of S. aureus and S. pseudintermedius infection, as well as provide valuable insights into the biology of phage-host interactions.
Highlights
Staphylococcus is a Gram-positive bacterium that causes many kinds of infections
ɸSP276 did not completely lose its infectivity toward wall teichoic acid (WTA)-free isolates, indicating that phage can use another component as a receptor. These findings indicated that all phages in this study utilize WTA in S. pseudintermedius and S. epidermidis as their receptor, but that the WTA of these bacteria is likely distinct from that of S. aureus
ɸSA039 requires the β-GlcNAc moiety in WTA of S. aureus, it can switch its receptor by acquiring spontaneous mutation in its receptor-binding protein (RBP)
Summary
S. aureus and S. pseudintermedius, are coagulase-positive bacteria that are notoriously pathogenic in humans and animals (Kloos and Bannerman 1994; Pompilio et al.2015). S. aureus is a commensal found on the skin and mucosae of humans, whereas S. pseudintermedius commonly inhabits dog skin. Both are common bacterial pathogens associated with chronic and recurrent skin infections that require long-term systemic antimicrobial therapy. Infection by S. aureus and S. pseudintermedius is becoming problematic due to the emergence of antibiotic-resistant strains, including methicillin-resistant (MRSA and MRSP) and vancomycinresistant strains (VRSA) (Enright et al 2002; Sakoulas et al 2005). Virulent bacteriophages that can kill a wide range of S. aureus hosts represent promising alternatives to conventional antibiotic treatment (Alves et al 2014; Iwano et al 2018; Azam and Tanji 2019a). The success of phage infection depends on its host specificity, which is often determined by the interaction between a phage receptor-binding protein (RBP) and its cognate receptor on the surface of the host cell (Hyman and Abedon 2010)
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