During an infection, parasites face a succession of challenges, each decisive for disease outcome. The diversity of challenges requires a series of parasite adaptations to successfully multiply and transmit from host to host. Thus, the pathogen genotypes which succeed during one step might be counter-selected in later stages of the infection. Using the bacteria Xenorhabdus nematophila and adult Drosophila melanogaster as hosts, we showed that such step-specific adaptations, here linked to GASP mutations in the X. nematophila master gene regulator lrp, exist and can trade-off with each other. We found that nonsense lrp mutations had lowered ability to resist the host immune response, while all classes of mutations in lrp were associated with a decrease in the ability to proliferate during early infection. We demonstrate that reduced proliferation of X. nematophila best explains diminished virulence in this infection model. Finally, decreased proliferation during the first step of infection is accompanied with improved proliferation during late infection, suggesting a trade-off between the adaptations to each step. Step-specific adaptations could play a crucial role in the chronic phase of infections in any diseases that show similar small colony variants (also known as SCV) to X. nematophila.

中文翻译：

---

GASP突变小菌落变异体在感染过程中的特定步骤适应性和权衡

在感染期间，寄生虫面临着一系列挑战，每种挑战都决定疾病的结果。挑战的多样性要求一系列寄生虫适应，才能成功地在宿主之间繁殖和传播。因此，在感染的后期阶段可能会反选在一个步骤中成功的病原体基因型。使用细菌Xenorhabdus nematophila和成年果蝇Drosophila melanogaster作为宿主，我们显示了这种与步骤相关的适应性，在这里与X. nematophila主基因调节剂lrp中的GASP突变有关，并且可以相互取舍。我们发现无意义的lrp突变降低了抵抗宿主免疫反应的能力，而lrp中的所有突变都与早期感染期间增殖能力的降低有关。我们证明减少的线虫嗜血杆菌的增殖最好地解释了这种感染模型中毒力下降。最后，在感染第一步的增殖减少与晚期感染的增殖改善有关，这表明在适应每个步骤之间需要权衡。在任何表现出与线虫嗜血杆菌相似的小菌落变体（也称为SCV）的疾病中，针对特定步骤的适应措施在感染的慢性阶段可能起关键作用。