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Espécies do género Chlamydia são caracterizadas como bactérias intracelulares obrigatórias, Gram-negativas capazes de causar diversas doenças em humanos e animais. Estes patogénicos possuem um ciclo de vida bifásico que se inicia com o corpo elementar (CE), a forma extracelular, e metabolicamente inerte de Chlamydia, com a capacidade de induzir a sua internalização. Após a entrada na célula hospedeira, o CE diferencia-se em corpo reticulado (CR), forma replicativa e metabolicamente activa. O processo pelo qual o CE invade as células é dependente do efector secretado pelo sistema secretor tipo III, designado por TarP (de Translocated actin-recruiting phosphoprotein). Este efector tem a capacidade de reestruturar o citoesqueleto de actina por um mecanismo de sinalização promovendo a invasão bacteriana. Sendo FAK (de Focal Adhesion kinase) uma molécula importante na regulação da dinâmica de actina, investigou-se a existência de um possível mecanismo de activação e recrutamento de FAK, por Chlamydia sp.. Utilizando duas técnicas diferentes de indução de sinalização a partir do TarP e o dos seus derivados, mostrou-se que uma nova região nesta proteína tem a capacidade de recrutar FAK, vinculina, e Arp2/3, culminando no recrutamento de actina. Mostrou-se igualmente que o recrutamento destas moléculas é induzido com a oligomerização da nova região de TarP, designada de LD. Concluindo, no presente trabalho, descreve-se um novo mecanismo de sinalização utilizado por várias espécies de Chlamydia.
Chlamydia species are Gram-negative obligate intracellular bacteria capable of causing several diseases in humans and animals. These pathogens have a unique biphasic development cycle that initiates with the elementary body (EB), the extracellular and metabolically inert form capable of inducing its internalization. Once inside the host cell, the EBs differentiate into a different form, the reticulate body (RB), which are the replicative and metabolically active form. The process by which the EBs invade cells is dependent on a type III secretion system effector called TarP (Translocated actin-recruiting phosphoprotein). TarP is known to modulate actin cytoskeleton by a signalling mechanism to promote bacterial invasion. Since FAK (Focal Adhesion kinase) is an important molecule in the regulation of actin dynamics, it was hypothesised that Chlamydia species have a pathway to induce activation and recruitment of FAK. Using two different approaches of inducing signalling from TarP and its derivatives, we show that a new motif within TarP is capable of recruiting FAK, vinculin and Arp2/3 leading to actin recruitment. We presented, as well, that the recruitment of these molecules are enhanced upon oligomerisation of the LD domain. Altogether, we described a new signalling pathway used by several chlamydial species.
Chlamydia species are Gram-negative obligate intracellular bacteria capable of causing several diseases in humans and animals. These pathogens have a unique biphasic development cycle that initiates with the elementary body (EB), the extracellular and metabolically inert form capable of inducing its internalization. Once inside the host cell, the EBs differentiate into a different form, the reticulate body (RB), which are the replicative and metabolically active form. The process by which the EBs invade cells is dependent on a type III secretion system effector called TarP (Translocated actin-recruiting phosphoprotein). TarP is known to modulate actin cytoskeleton by a signalling mechanism to promote bacterial invasion. Since FAK (Focal Adhesion kinase) is an important molecule in the regulation of actin dynamics, it was hypothesised that Chlamydia species have a pathway to induce activation and recruitment of FAK. Using two different approaches of inducing signalling from TarP and its derivatives, we show that a new motif within TarP is capable of recruiting FAK, vinculin and Arp2/3 leading to actin recruitment. We presented, as well, that the recruitment of these molecules are enhanced upon oligomerisation of the LD domain. Altogether, we described a new signalling pathway used by several chlamydial species.