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Analysis host-recognition mechanism of staphylococcal kayvirus ɸSA039 reveals a novel strategy that protects Staphylococcus aureus against infection by Staphylococcus pseudintermedius Siphoviridae phages

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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.

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Acknowledgments

We thank Professor Kenji Kurokawa at the Faculty of Pharmaceutical Science of Nagasaki International University for providing us with the deletion mutant of RN4220.

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Authors and Affiliations

  1. School of Life Science and Technology, Tokyo Institute of Technology, 4259 J2-15 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan

    Aa Haeruman Azam, Kenji Kadoi, Kazuhiko Miyanaga & Yasunori Tanji

  2. Division of Bacteriology, Department of Infection and Immunity, Faculty of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan

    Aa Haeruman Azam & Longzhu Cui

  3. Graduate School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyoudaimidorimachi, Ebetsu-shi, Hokkaido, 069-0836, Japan

    Masaru Usui & Yutaka Tamura

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Azam, A.H., Kadoi, K., Miyanaga, K. et al. Analysis host-recognition mechanism of staphylococcal kayvirus ɸSA039 reveals a novel strategy that protects Staphylococcus aureus against infection by Staphylococcus pseudintermedius Siphoviridae phages. Appl Microbiol Biotechnol 103, 6809–6823 (2019). https://doi.org/10.1007/s00253-019-09940-7

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