Crowe Logan P, Gioseffi Anna, Bertolini Mayara S, Docampo Roberto
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
Pathogens. 2024 Sep 9;13(9):776. doi: 10.3390/pathogens13090776.
is the etiologic agent of Chagas disease, an infection that can lead to the development of cardiac fibrosis, which is characterized by the deposition of extracellular matrix (ECM) components in the interstitial region of the myocardium. The parasite itself can induce myofibroblast differentiation of cardiac fibroblast in vitro, leading to increased expression of ECM. Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate that can also induce myofibroblast differentiation and deposition of ECM components and is highly abundant in . PolyP can modify proteins post-translationally by non-enzymatic polyphosphorylation of lysine residues of poly-acidic, serine-(S) and lysine (K)-rich (PASK) motifs. In this work, we used a bioinformatics screen and identified the presence of PASK domains in several surface proteins of . We also detected polyP in the external surface of its different life cycle stages and confirmed the stimulation of host cell fibrosis by trypomastigote infection. However, we were not able to detect significant secretion of the polymer or activation of transforming growth factor beta (TGF-β), an important factor for the generation of fibrosis by inorganic polyP- or trypomastigote-conditioned medium.
是恰加斯病的病原体，这种感染可导致心脏纤维化的发展，其特征是细胞外基质（ECM）成分在心肌间质区域沉积。该寄生虫本身可在体外诱导心脏成纤维细胞向肌成纤维细胞分化，导致ECM表达增加。无机多聚磷酸盐（polyP）是正磷酸盐的线性聚合物，也可诱导肌成纤维细胞分化和ECM成分沉积，且在……中高度丰富。PolyP可通过对富含多酸性、丝氨酸（S）和赖氨酸（K）的（PASK）基序的赖氨酸残基进行非酶促多磷酸化来翻译后修饰蛋白质。在这项工作中，我们通过生物信息学筛选，在……的几种表面蛋白中鉴定出了PASK结构域的存在。我们还在其不同生命周期阶段的外表面检测到了polyP，并证实了锥鞭毛体感染对宿主细胞纤维化的刺激作用。然而，我们未能检测到该聚合物的显著分泌或转化生长因子β（TGF-β）的激活，TGF-β是无机polyP或锥鞭毛体条件培养基产生纤维化的重要因子。
