Decolonizing drug-resistant E. coli with phage and probiotics: breaking the frequency-dependent dominance of residents.
Decolonizing drug-resistant E. coli with phage and probiotics: breaking the frequency-dependent dominance of residents.
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DOI：
10.1099/mic.0.001352
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发表时间：
2023-07
期刊：
影响因子：
2.8
通讯作者：
Raymond, Ben
中科院分区：
文献类型：
--
作者：
Forsyth, Jessica H.;Barron, Natalie L.;Scott, Lucy;Watson, Bridget N. J.;Chisnall, Matthew A. W.;Meaden, Sean;van Houte, Stineke;Raymond, Ben
肠道细菌中广泛存在的抗生素耐药性给人类健康带来了持续的挑战。常驻耐药微生物可以阻止临床干预，在术后伤口定植，将耐药性传递给病原体或在常规干预（如导管插入术）后转移到更有害的小生境。因此，加速清除耐药细菌或积极使特定谱系从宿主身上去殖民化可能会带来许多长期好处。然而，通过与益生菌竞争来去除常驻细菌，例如，会带来许多生态挑战。常驻微生物可能具有生理和数量优势，并且基于细菌素或其他分泌拮抗剂的竞争预期通过正频率依赖性给予优势伴侣优势。由于一个狭窄的范围， 大肠杆菌 尽管这些基因型（主要是属于克隆组ST 131的那些）引起显著比例的多药耐药感染，但该组呈现了用噬菌体去殖民化的有希望的靶标，因为窄宿主范围的病毒捕食可能导致特定基因型的选择性去除。在这项研究中，我们测试了ST 131特异性噬菌体和来自众所周知的益生菌的竞争的组合如何 E.杆菌 尼氏应变可以取代 E.杆菌 ST131在体外需氧和厌氧生长条件下的生长。我们发现，噬菌体的加入能够打破数量上占优势的ST 131分离株的频率依赖性优势。此外，竞争的增加 E.杆菌 Nissle可以将噬菌体抑制ST131的能力提高两个数量级。低成本的噬菌体抗性在这些实验中很容易进化，并且不受益生菌竞争者存在的抑制。然而，噬菌体和益生菌的组合在多次转移中以及在有氧和厌氧生长条件下产生了稳定的ST131长期抑制。因此，噬菌体和益生菌的组合具有真实的潜力，可以加速去除耐药的靶细胞。
Widespread antibiotic resistance in commensal bacteria creates a persistent challenge for human health. Resident drug-resistant microbes can prevent clinical interventions, colonize wounds post-surgery, pass resistance traits to pathogens or move to more harmful niches following routine interventions such as catheterization. Accelerating the removal of resistant bacteria or actively decolonizing particular lineages from hosts could therefore have a number of long-term benefits. However, removing resident bacteria via competition with probiotics, for example, poses a number of ecological challenges. Resident microbes are likely to have physiological and numerical advantages and competition based on bacteriocins or other secreted antagonists is expected to give advantages to the dominant partner, via positive frequency dependence. Since a narrow range of Escherichia coli genotypes (primarily those belonging to the clonal group ST131) cause a significant proportion of multidrug-resistant infections, this group presents a promising target for decolonization with bacteriophage, as narrow-host-range viral predation could lead to selective removal of particular genotypes. In this study we tested how a combination of an ST131-specific phage and competition from the well-known probiotic E. coli Nissle strain could displace E. coli ST131 under aerobic and anaerobic growth conditions in vitro. We showed that the addition of phage was able to break the frequency-dependent advantage of a numerically dominant ST131 isolate. Moreover, the addition of competing E. coli Nissle could improve the ability of phage to suppress ST131 by two orders of magnitude. Low-cost phage resistance evolved readily in these experiments and was not inhibited by the presence of a probiotic competitor. Nevertheless, combinations of phage and probiotic produced stable long-term suppression of ST131 over multiple transfers and under both aerobic and anaerobic growth conditions. Combinations of phage and probiotic therefore have real potential for accelerating the removal of drug-resistant commensal targets.
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DOI：
10.1073/pnas.1919888117
发表时间：
2020-05-26
影响因子：
11.1
作者：
Burmeister, Alita R.;Fortier, Abigail;Turner, Paul E.
通讯作者：
Turner, Paul E.
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：
3.7
作者：
Budič M;Rijavec M;Petkovšek Z;Zgur-Bertok D
通讯作者：
Zgur-Bertok D
DOI：
10.1073/pnas.78.10.6324
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHAO, L;LEVIN, BR
通讯作者：
LEVIN, BR
影响因子：
11.8
作者：
Corbellino, Mario;Kieffer, Nicolas;Poirel, Laurent
通讯作者：
Poirel, Laurent