Bacteriophage Cocktail and Microcin-Producing Probiotic Escherichia coli Protect Mice Against Gut Colonization With Multidrug-Resistant Escherichia coli Sequence Type 131.
Bacteriophage Cocktail and Microcin-Producing Probiotic Escherichia coli Protect Mice Against Gut Colonization With Multidrug-Resistant Escherichia coli Sequence Type 131.
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DOI：
10.3389/fmicb.2022.887799
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
需要采取非抗生素措施，以降低耐多药生物体的感染率，包括消除导致这种菌株传播和导致复发性感染的肠道宿主。在这里，我们测试了预先选择的噬菌体和工程改造的产生微球蛋白C7的益生菌大肠杆菌Nissle-1917菌株的混合物，以减少大肠杆菌的肠道定植的能力。大肠埃希菌131（ST 131）-H30 R是肠外临床大肠埃希菌中MDRO的主要克隆群。大肠杆菌分离株。尽管噬菌体混合物在体外和皮下脓毒症的鼠模型中对ST 131-H30 R菌株高度有效，但其对靶ST 131-H30 R菌株的肠道定殖仅具有微弱和短暂的有效性（在d + 1降低0.5 log 10：p < 0.001;在d + 4及以后无显著作用）。益生菌菌株虽然在体外对ST 131-H30 R也具有高活性，但尽管其在粪便中大量存在，但对ST 131-H30 R肠道定殖无效。然而，尽管当单独施用时不能作为去定殖剂，但当共施用时，噬菌体混合物和益生菌菌株表现出对抗ST 131-H30 R肠道定殖的显著协同作用。这种组合效应在d + 1时最明显（3.3 log 10目标菌株降低：p < 0.001），并持续至d + 7（0.5 log 10降低; p < 0.02）。尽管到d + 10时ST 131-H30 R负荷完全恢复，但这些发现提供了噬菌体加益生菌组合施用以减少或可能防止MDRO在高风险个体中的肠道定殖的概念证据。
Non-antibiotic measures are needed to reduce the rate of infections due to multidrug-resistant organisms (MDROs), including by eliminating the commensal reservoir that underlies such strains’ dissemination and leads to recurrent infections. Here, we tested a cocktail of pre-selected bacteriophages and an engineered microcin C7-producing probiotic Escherichia coli Nissle-1917 strain for their ability to reduce gut colonization by an E. coli strain from sequence type 131 (ST131)-H30R, which is the major clonal group of MDROs among extraintestinal clinical E. coli isolates. Although the bacteriophage cocktail was highly effective against ST131-H30R strains both in vitro and in a murine model of subcutaneous sepsis, it was only weakly and transiently effective against gut colonization by the target ST131-H30R strain (0.5 log10 decrease on d + 1: p < 0.001; no significant effect on d + 4 and beyond). The probiotic strain, while also highly active against ST131-H30R in vitro, was ineffective against ST131-H30R gut colonization despite its abundant presence in feces. Nonetheless, despite failing as decolonizing agents when administered separately, when co-administered the bacteriophage cocktail and probiotic strain exhibited striking synergy against ST131-H30R gut colonization. This combinatory effect was most pronounced on d + 1 (3.3 log10 target strain decrease: p < 0.001), and persisted until d + 7 (0.5 log10 decrease; p < 0.02.). Although by d + 10 the ST131-H30R load was fully restored, these findings provide proof of concept for combined bacteriophage-plus-probiotic administration to reduce or, possibly, to prevent gut colonization with MDROs in high-risk individuals.
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影响因子：
4.6
作者：
Green SI;Kaelber JT;Ma L;Trautner BW;Ramig RF;Maresso AW
通讯作者：
Maresso AW
影响因子：
3.7
作者：
Merino I;Porter SB;Johnston BD;Clabots C;Shaw E;Horcajada JP;Cantón R;Ruiz-Garbajosa P;Johnson JR;ITUBRAS-GEIH group
通讯作者：
ITUBRAS-GEIH group
影响因子：
4.6
作者：
Bernasconi, Odette J.;Campos-Madueno, Edgar, I;Endimiani, Andrea
通讯作者：
Endimiani, Andrea
影响因子：
4.9
作者：
Lescat, Mathilde;Launay, Adrien;Tenaillon, Olivier
通讯作者：
Tenaillon, Olivier
影响因子：
5.2
作者：
Merino, Irene;Porter, Stephen B.;Johnson, James R.
通讯作者：
Johnson, James R.