Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA
Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
mSphere. 2020 Sep 9;5(5):e00594-20. doi: 10.1128/mSphere.00594-20.
The major surface lipophosphoglycan (LPG) of parasites is critical to vector competence in restrictive sand fly vectors in mediating attachment to the midgut epithelium, considered essential to parasite survival and development. However, the relevance of LPG for sand flies that harbor multiple species of remains elusive. We tested binding of wild-type (WT), LPG-defective (Δ mutants), and add-back (Δ+) lines to sand fly midguts and their survival in sand flies WT parasites attached to the midgut , with late-stage parasites binding to midguts in significantly higher numbers than were seen with early-stage promastigotes. Δ mutants did not bind to midguts, and this was rescued in the Δ+ lines, indicating that midgut binding is mediated by LPG. When sand flies were infected with the WT or Δ or Δ+ line of the BH46 or BA262 strains, the BH46 Δ mutant, but not the BA262 Δ mutant, survived and grew to numbers similar to those seen with the WT and Δ+ lines. Exposure of BH46 and BA262 Δ mutants to blood-engorged midgut extracts led to mortality of the BA262 Δ but not the BH46 Δ parasites. These findings suggest that LPG protects parasites on a strain-specific basis early in infection, likely against toxic components of blood digestion, but that it is not necessary to prevent evacuation along with the feces in the permissive vector It is well established that the presence of LPG is sufficient to define the vector competence of restrictive sand fly vectors with respect to parasites. However, the permissiveness of other sand flies with respect to multiple species suggests that other factors might define vector competence for these vectors. In this study, we investigated the underpinnings of survival and development in its natural vector, We found that LPG-mediated midgut binding persists in late-stage parasites. This observation is of relevance for the understanding of vector-parasite molecular interactions and suggests that only a subset of infective metacyclic-stage parasites (metacyclics) lose their ability to attach to the midgut, with implications for parasite transmission dynamics. However, our data also demonstrate that LPG is not a determining factor in retention in the midgut of , a permissive vector. Rather, LPG appears to be more important in protecting some parasite strains from the toxic environment generated during blood meal digestion in the insect gut. Thus, the relevance of LPG in parasite development in permissive vectors appears to be a complex issue and should be investigated on a strain-specific basis.
寄生虫的主要表面脂磷壁酸（LPG）对于媒介沙蝇中有限的媒介能力至关重要，它介导附着到中肠上皮，被认为是寄生虫存活和发育所必需的。然而，LPG 对于携带多种物种的沙蝇的相关性仍然难以捉摸。我们测试了野生型（WT）、LPG 缺陷（Δ突变体）和回补（Δ+）系与沙蝇中肠的结合，以及 WT 寄生虫在沙蝇中的存活情况，晚期寄生虫与中肠的结合数量明显高于早期前鞭毛体。Δ 突变体不能与中肠结合，而在 Δ+系中可以恢复，表明中肠结合是由 LPG 介导的。当沙蝇感染 BH46 或 BA262 株的 WT 或 Δ 或 Δ+系时，BH46Δ 突变体，但不是 BA262Δ 突变体，存活并生长到与 WT 和 Δ+系相似的数量。暴露于 BH46 和 BA262Δ 突变体的血饱食中肠提取物导致 BA262Δ 寄生虫死亡，但 BH46Δ 寄生虫不会。这些发现表明，LPG 以菌株特异性为基础，在感染早期保护寄生虫，可能针对血液消化的有毒成分，但它不是防止在允许的载体中与粪便一起排出所必需的。
已经确定 LPG 的存在足以定义限制沙蝇媒介对寄生虫的媒介能力。然而，其他沙蝇对多种寄生虫的允许性表明，其他因素可能定义了这些载体的媒介能力。在这项研究中，我们研究了它在其自然媒介中的生存和发育的基础。我们发现，LPG 介导的中肠结合在晚期寄生虫中仍然存在。这一观察结果对于理解媒介-寄生虫分子相互作用具有重要意义，并表明只有一部分感染性的循环期寄生虫（循环期）失去了附着中肠的能力，这对寄生虫传播动力学有影响。然而，我们的数据还表明，LPG 不是寄生虫在允许的载体中的中肠保留的决定因素。相反，LPG 似乎在保护某些寄生虫株免受昆虫肠道中血液消化产生的有毒环境方面更为重要。因此，LPG 在允许的载体中寄生虫发育的相关性似乎是一个复杂的问题，应该在菌株特异性的基础上进行研究。
