Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism.
Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism.
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DOI：
10.1128/iai.00020-16
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发表时间：
2016-06
影响因子：
3.1
通讯作者：
Krachler AM
中科院分区：
文献类型：
--
作者：
Al-Saedi F;Stones DH;Vaz DP;Krachler AM
病原体与宿主细胞的黏附是感染过程中的一个关键过程，抑制病原体黏附是预防传染病的一条很有前途的途径。我们以前已经证明，多价黏附分子(MAM)在病原菌和共生菌中都很丰富，介导与宿主细胞的早期附着，并可促进毒力。在这里，我们研究了在组织培养感染模型中，在其表面表达共生MAM的工程菌在防止病原体附着和病原体介导的细胞毒性方面的有效性。通过与完全合成的黏附抑制剂的结果比较，我们能够剖析黏附和种间拮抗对一系列不同病原体感染总结局的个体贡献。我们发现，工程菌击败病原体的潜力并不总是完全取决于它阻碍宿主附着的能力，但根据病原物种的不同，还可能包括种间拮抗的元素，例如对营养的竞争，以及它因产生抗微生物因子而导致适应性丧失的能力。
Pathogen attachment to host cells is a key process during infection, and inhibition of pathogen adhesion is a promising approach to the prevention of infectious disease. We have previously shown that multivalent adhesion molecules (MAMs) are abundant in both pathogenic and commensal bacterial species, mediate early attachment to host cells, and can contribute to virulence. Here, we investigated the efficacy of an engineered bacterium expressing a commensal MAM on its surface in preventing pathogen attachment and pathogen-mediated cytotoxicity in a tissue culture infection model. We were able to dissect the individual contributions of adhesion and interspecific antagonism on the overall outcome of infection for a range of different pathogens by comparison with the results obtained with a fully synthetic adhesion inhibitor. We found that the potential of the engineered bacterium to outcompete the pathogen is not always solely dependent on its ability to hinder host attachment but, depending on the pathogenic species, may also include elements of interspecific antagonism, such as competition for nutrients and its ability to cause a loss of fitness due to production of antimicrobial factors.