Vázquez Cristina Lourdes, Bianco María Verónica, Blanco Federico Carlos, Forrellad Marina Andrea, Gutierrez Maximiliano Gabriel, Bigi Fabiana
Instituto de Biotecnología, CICVyA-INTA, Nicolás Repetto y De Los Reseros, Buenos Aires, Argentina.
Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, United Kingdom.
Infect Immun. 2017 Feb 23;85(3). doi: 10.1128/IAI.00720-16. Print 2017 Mar.
causes tuberculosis in a wide variety of mammals, with strong tropism for cattle and eventually humans. P27, also called LprG, is among the proteins involved in the mechanisms of the virulence and persistence of and Here, we describe a novel function of P27 in the interaction of with its natural host cell, the bovine macrophage. We found that a deletion in the operon impairs the replication of in bovine macrophages. Importantly, we show for the first time that arrests phagosome maturation in a process that depends on P27. This effect is P27 specific since complementation with wild-type but not fully restored the wild-type phenotype of the mutant strain; this indicates that P55 plays no important role during the early events of infection. In addition, we also showed that the presence of P27 from decreases the association of LAMP-3 with bead phagosomes, indicating that P27 itself blocks phagosome-lysosome fusion by modulating the traffic machinery in the cell host.
可在多种哺乳动物中引发结核病，对牛以及最终对人类具有很强的嗜性。P27，也称为LprG，是参与其毒力和持续性机制的蛋白质之一。在此，我们描述了P27在其与天然宿主细胞牛巨噬细胞相互作用中的一种新功能。我们发现操纵子中的缺失会损害在牛巨噬细胞中的复制。重要的是，我们首次表明在一个依赖P27的过程中阻止吞噬体成熟。这种效应是P27特异性的，因为用野生型互补但不是完全恢复了突变株的野生型表型；这表明P55在感染的早期事件中不发挥重要作用。此外，我们还表明来自的P27的存在会降低LAMP - 3与珠子吞噬体的结合，表明P27本身通过调节细胞宿主中的运输机制来阻断吞噬体 - 溶酶体融合。
