Within the sand fly,利什曼尼亚transform into a number of flagellatedpromastigoteforms, each with specific roles to play in colonising the vector for onward transmission. However, to survive in a sand fly is not straightforward.
The problem
As利什曼尼亚live exclusively in the sand fly gut this can present some unique problems for the parasite. Firstly, they need to resist the hostile proteolytic environment of the bloodmeal as it is digested and survive assault from oxidative radicals. Next, they have to get out of the digested bloodmeal, which is encased in a chitinous peritrophic matrix, before the sand fly defecates. Thirdly, they must resist being lost from the sand fly when it defecates and find their way to the sand fly mouthparts to develop into its infectious form, the metacyclic promastigote. Here they face the final challenge of making their way into the vertebrate host’s skin against the flow of an incoming meal of fresh blood without being swept back into the midgut.
中肠附件
在沙蝇中生存的最关键步骤之一是抵制被消化的血液隔离。
去做这个利什曼尼亚在涉及寄生虫“粘附素”，脂磷酸聚糖（LPG）的过程中，将自己锚定在中肠的微绒毛之间。这种糖脂层覆盖了整个前鞭毛脂蛋白的表面，当寄生虫分化为传染性的Metacyclic promastigote形式时，它会进行显着的修饰。这防止了肠道的重新连接，从而为他们提供了传播的最佳机会。
Epidemiologically, sand flies fall into two categories – they are either restrictive or permissive. In restrictive sand fly species, attachment is provided by LPG of nectomonad and leptomonad promastigotes in the early- to mid-phase of利什曼尼亚development binding to a gut expressed lectin; resulting in the selective transmission of only one利什曼尼亚species. In contrast, most sand flies are more permissive and can host a wide range of利什曼尼亚通过未知机制的物种。然而，其附着的一个线索脱颖而出 - 允许的砂蝇用粘液排成其肠道，其中含有丰富的特定糖N-乙酰基半乳糖胺（GalNAC）。
Atomic Force Microscopy
我们在寄生学家，生物物理学家和合成化学家之间的合作工作，published in the Royal Society of Chemistry, explains how force spectroscopy was used to probe the surface of nectomonad and metacyclic promastigotes of利什曼尼亚mexicanawith tips coated with a GalNAc mimic. We measured利什曼尼亚通过使用原子力显微镜（AFM）的粘附，能够测量一些piconewton（PN）的粘附。AFM包含一个微小的尖端，该尖端通过悬臂支撑连接到其控制器上。
当尖端与表面接触时，悬臂会弯曲一点。可以测量这种弯曲，并从中计算出相互作用的力，并为每个寄生虫构建表面粘附的纳米级图。
Using AFM, we tested the hypothesis that LPG may still be involved in attachment to permissive sand fly guts through glycan-glycan interactions – i.e. not involving lectins. We found that there was direct interaction between this GalNAc and LPG which was restricted to the gut-adherent promastigote stages and could be blocked by the introduction of excess GalNAc. This new mode of binding is comparable to the attachment of pili of gut-pathogenic bacteria to the mucus of human intestinal epithelia and offers a new model to study the competency of sand flies for利什曼尼亚和他们的传输。
传输封锁
Data collected from these experiments and previously published studies on利什曼尼亚沙蝇中的感染使我们能够基于该机制数学对传播阻断疫苗的可能性能进行建模。我们发现，这种疫苗的性能很好，尽管如果疫苗不够有效，它会加剧问题。需要进一步的研究来取笑这种关系，以指导寻找最合适的疫苗候选者的搜索。
A new hypothesis for the competency of permissive sand fly vectors?
到目前为止，尚不清楚中肠粘附有多少有助于Leishmania传播的矢量能力。但是发现利什曼尼亚can use their LPG to directly bind to sugars is a big step forward in our understanding of the interaction between利什曼尼亚parasites and sand flies and, possibly, the vertebrate host following transmission.
Looking to the future, what excites us the most is the enormous potential biophysics and interdisciplinary research has to offer to explore vector-parasite and vector-parasite-host interactions.
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