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噬菌体鸡尾酒两种给药途径在减少鸡源大肠杆菌和空肠弯曲菌数量的体内疗效。

The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens.

机构信息

Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.

出版信息

BMC Microbiol. 2010 Sep 1;10:232. doi: 10.1186/1471-2180-10-232.

Abstract

BACKGROUND

Poultry meat is one of the most important sources of human campylobacteriosis, an acute bacterial enteritis which is a major problem worldwide. Campylobacter coli and Campylobacter jejuni are the most common Campylobacter species associated with this disease. These pathogens live in the intestinal tract of most avian species and under commercial conditions they spread rapidly to infect a high proportion of the flock, which makes their treatment and prevention very difficult. Bacteriophages (phages) are naturally occurring predators of bacteria with high specificity and also the capacity to evolve to overcome bacterial resistance. Therefore phage therapy is a promising alternative to antibiotics in animal production. This study tested the efficacy of a phage cocktail composed of three phages for the control of poultry infected with C. coli and C. jejuni. Moreover, it evaluated the effectiveness of two routes of phage administration (by oral gavage and in feed) in order to provide additional information regarding their future use in a poultry unit.

RESULTS

The results indicate that experimental colonisation of chicks was successful and that the birds showed no signs of disease even at the highest dose of Campylobacter administered. The phage cocktail was able to reduce the titre of both C. coli and C. jejuni in faeces by approximately 2 log10 cfu/g when administered by oral gavage and in feed. This reduction persisted throughout the experimental period and neither pathogen regained their former numbers. The reduction in Campylobacter titre was achieved earlier (2 days post-phage administration) when the phage cocktail was incorporated in the birds' feed. Campylobacter strains resistant to phage infection were recovered from phage-treated chickens at a frequency of 13%. These resistant phenotypes did not exhibit a reduced ability to colonize the chicken guts and did not revert to sensitive types.

CONCLUSIONS

Our findings provide further evidence of the efficacy of phage therapy for the control of Campylobacter in poultry. The broad host range of the novel phage cocktail enabled it to target both C. jejuni and C. coli strains. Moreover the reduction of Campylobacter by approximately 2 log10cfu/g, as occurred in our study, could lead to a 30-fold reduction in the incidence of campylobacteriosis associated with consumption of chicken meals (according to mathematical models). To our knowledge this is the first report of phage being administered in feed to Campylobacter-infected chicks and our results show that it lead to an earlier and more sustainable reduction of Campylobacter than administration by oral gavage. Therefore the present study is of extreme importance as it has shown that administering phages to poultry via the food could be successful on a commercial scale.

摘要

背景

禽肉是人类弯曲菌病的最重要来源之一,弯曲菌病是一种急性细菌性肠炎,是全世界的一个主要问题。大肠弯曲菌和空肠弯曲菌是与这种疾病最相关的最常见弯曲菌。这些病原体存在于大多数禽类的肠道中,在商业条件下,它们迅速传播,感染了很大比例的禽类,这使得它们的治疗和预防非常困难。噬菌体(噬菌体)是天然存在的细菌捕食者,具有高度特异性,并且有能力进化以克服细菌耐药性。因此,噬菌体疗法是动物生产中抗生素的一种有前途的替代品。本研究测试了由三种噬菌体组成的噬菌体鸡尾酒控制感染大肠弯曲菌和空肠弯曲菌的禽类的功效。此外,它评估了通过口服灌胃和饲料两种途径给予噬菌体的有效性,以便为将来在禽类单位中使用噬菌体提供更多信息。

结果

结果表明,实验性雏鸡定植是成功的,即使给予最高剂量的弯曲菌,鸟类也没有出现疾病迹象。当通过口服灌胃和饲料给予噬菌体鸡尾酒时,它能够使粪便中两种大肠弯曲菌和空肠弯曲菌的滴度降低约 2 个对数 10 cfu/g。这种减少在整个实验期间持续存在,并且没有一种病原体恢复到以前的数量。当噬菌体鸡尾酒掺入鸟类饲料中时,噬菌体对弯曲菌滴度的减少更早(噬菌体给药后 2 天)。从接受噬菌体治疗的鸡中回收的弯曲菌耐药株的频率为 13%。这些耐药表型没有表现出降低定植鸡肠道的能力,也没有恢复为敏感类型。

结论

我们的发现为噬菌体疗法控制禽源弯曲菌的功效提供了进一步的证据。新型噬菌体鸡尾酒的广泛宿主范围使其能够靶向空肠弯曲菌和大肠弯曲菌。此外,我们研究中发生的大约 2 个对数 10 cfu/g 的弯曲菌减少可能导致与食用鸡肉餐相关的弯曲菌病发病率降低 30 倍(根据数学模型)。据我们所知,这是首次报道将噬菌体给药于感染弯曲菌的雏鸡饲料中,我们的结果表明,与口服灌胃相比,它导致更早和更可持续的弯曲菌减少。因此,本研究非常重要,因为它表明通过食物向禽类给药噬菌体在商业规模上可能是成功的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97f0/2940857/cc38acca2f78/1471-2180-10-232-1.jpg

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