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Yamashita, W.

Publications and source records attributed to Yamashita, W..

2 recordsLinked to original sources

Viruses encode tRNA and anti-retron to evade bacterial immunity

Retrons are bacterial genetic retroelements that encode reverse transcriptase capable of producing multicopy single-stranded DNA (msDNA) and function as antiphage defense systems. Phages employ several strategies to counter the host defense systems, but no mechanisms for evading retrons are known. Here, we show that tRNATyr and Rad (retron anti-defense) of T5 phage family inhibit the defense activity of retron 78 and a broad range of retrons, respectively. The effector protein of retron 78, ptuAB, specifically degraded tRNATyr leading abortive infection, but phage countervailed this defense by supplying tRNATyr. Rad inhibited retron function by degrading noncoding RNA, the precursor of msDNA. In summary, we demonstrated that viruses encode at least two independent strategies for overcoming bacterial defense systems: anti-defense, such as Rad, and defense canceler, like tRNA.

microbiology↗

Selective bacteriophages reduce the emergence of resistant bacteria in the bacteriophage-antibiotic combination therapy

Escherichia coli O157:H7 is a globally important foodborne pathogen that affects food safety. Antibiotic administration against O157:H7 may contribute to the exacerbation of hemolytic uremic syndrome (HUS) and antibiotic-resistant strains increase; therefore, bacteriophage therapy (phage therapy) is considered a useful alternative. In the treatment of resistant bacterial infections, combination therapy with bacteriophages and antibiotics, taking advantage of the benefits of both agents, has been suggested to be effective in inhibiting the emergence of antimicrobial-resistant strains; however, its effectiveness against O157:H7 is not well understood. In this study, we isolated SP015, a phage that infects O157:H7, and compared the combined effect of the bacteriophage and fosfomycin (FOM) with that of the PP01 phage. Genomic analysis revealed that FOM exerts its antibacterial activity through glycerol-3-phosphate transporter (GlpT) and hexose phosphate transporter (UhpT) proteins, and the receptors of PP01 and SP015 phages are the outer membrane protein C (OmpC) and ferrichrome outer membrane transporter protein (FhuA), respectively. Experiments with knockout strains have suggested that FOM also uses OmpC, the receptor for PP01, as a transporter. This may explain why the combination treatment with PP01 resulted in a faster emergence of resistance than the combination treatment with SP015. We propose that phage-antibiotic combination therapy requires careful selection of the phage to be used.

microbiology↗