Salmonella enteritidis acquires phage resistance through a point mutation in rfbD but loses some of its environmental adaptability

文献类型： 外文期刊

第一作者： Zeng, Yukun

作者： Zeng, Yukun;Li, Ping;Liu, Shenglong;Shen, Mangmang;Zhou, Xin;Zeng, Yukun;Zhou, Xin;Zeng, Yukun;Zhou, Xin;Liu, Yuqing

作者机构：

关键词： Salmonella enteritidis; rfbD gene; point mutation; phage resistance; environmental adaptability

期刊名称：VETERINARY RESEARCH （ 影响因子：3.7； 五年影响因子：3.8 ）

ISSN： 0928-4249

年卷期： 2024 年 55 卷 1 期

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收录情况： SCI

摘要： Phage therapy holds promise as an alternative to antibiotics for combating multidrug-resistant bacteria. However, host bacteria can quickly produce progeny that are resistant to phage infection. In this study, we investigated the mechanisms of bacterial resistance to phage infection. We found that Rsm1, a mutant strain of Salmonella enteritidis (S. enteritidis) sm140, exhibited resistance to phage Psm140, which was originally capable of lysing its host at sm140. Whole genome sequencing analysis revealed a single nucleotide mutation at position 520 (C -> T) in the rfbD gene of Rsm1, resulting in broken lipopolysaccharides (LPS), which is caused by the replacement of CAG coding glutamine with a stop codon TAG. The knockout of rfbD in the sm140 Delta rfbD strain caused a subsequent loss of sensitivity toward phages. Furthermore, the reintroduction of rfbD in Rsm1 restored phage sensitivity. Moreover, polymerase chain reaction (PCR) amplification of rfbD in 25 resistant strains revealed a high percentage mutation rate of 64% within the rfbD locus. We assessed the fitness of four bacteria strains and found that the acquisition of phage resistance resulted in slower bacterial growth, faster sedimentation velocity, and increased environmental sensitivity (pH, temperature, and antibiotic sensitivity). In short, bacteria mutants lose some of their abilities while gaining resistance to phage infection, which may be a general survival strategy of bacteria against phages. This study is the first to report phage resistance caused by rfbD mutation, providing a new perspective for the research on phage therapy and drug-resistant mechanisms.

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