Loss-of-Function Mutations in epaR Confer Resistance to ϕNPV1 Infection in Enterococcus faecalis OG1RF.
Loss-of-Function Mutations in epaR Confer Resistance to ϕNPV1 Infection in Enterococcus faecalis OG1RF.
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DOI：
10.1128/aac.00758-18
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发表时间：
2018-10
影响因子：
4.9
通讯作者：
Palmer KL
中科院分区：
文献类型：
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作者：
Ho K;Huo W;Pas S;Dao R;Palmer KL
粪肠球菌是一种存在于人体胃肠道的革兰氏阳性条件致病菌。由于临床分离的肠球菌对抗生素的耐药率很高，因此使用噬菌体治疗肠球菌感染和使耐药肠球菌的高危患者去克隆的兴趣正在上升。粪肠球菌是一种存在于人体胃肠道的革兰氏阳性条件致病菌。由于临床分离的肠球菌对抗生素的耐药率很高，因此使用噬菌体治疗肠球菌感染和使耐药肠球菌的高危患者去克隆的兴趣正在上升。细菌可以进化出对噬菌体的抵抗力，但关于粪肠球菌的这些机制的已发表信息很少。在这份报告中，我们确定了粪肠球菌对噬菌体NPV1(ϕNPV1)的抗性的遗传决定因素。我们发现，EPAR的功能缺失突变通过阻断噬菌体吸附来增强ϕ对NPV1的抗性。我们将噬菌体不能吸附的原因归因于EPAR失活菌株中胞外聚合物的修饰或丢失。抗噬菌体EPAR突变体表现出对达托霉素和渗透胁迫的敏感性增加。我们的结果表明，粪肠球菌OG1RF在体外对ϕNPV1的自发耐药是有代价的。
Enterococcus faecalis is a Gram-positive opportunistic pathogen that inhabits the human gastrointestinal tract. Because of the high frequency of antibiotic resistance among Enterococcus clinical isolates, interest in using phage to treat enterococcal infections and to decolonize high-risk patients for antibiotic-resistant Enterococcus is rising. Enterococcus faecalis is a Gram-positive opportunistic pathogen that inhabits the human gastrointestinal tract. Because of the high frequency of antibiotic resistance among Enterococcus clinical isolates, interest in using phage to treat enterococcal infections and to decolonize high-risk patients for antibiotic-resistant Enterococcus is rising. Bacteria can evolve phage resistance, but there is little published information on these mechanisms in E. faecalis. In this report, we identified genetic determinants of E. faecalis resistance to phage NPV1 (ϕNPV1). We found that loss-of-function mutations in epaR confer ϕNPV1 resistance by blocking phage adsorption. We attribute the inability of the phage to adsorb to the modification or loss of an extracellular polymer in strains with inactivated epaR. Phage-resistant epaR mutants exhibited increased daptomycin and osmotic stress susceptibilities. Our results demonstrate that in vitro spontaneous resistance to ϕNPV1 comes at a cost in E. faecalis OG1RF.