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1.
Eur J Cell Biol ; 102(4): 151359, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37683588

RESUMO

Staphylococcus aureus, a Gram-positive bacterial pathogen, is an urgent health threat causing a wide range of clinical infections. Originally viewed as a strict extracellular pathogen, accumulating evidence has revealed S. aureus to be a facultative intracellular pathogen subverting host cell signalling to support invasion. The majority of clinical isolates produce fibronectin-binding proteins A and B (FnBPA and FnBPB) to interact with host integrin α5ß1, a key component of focal adhesions. S. aureus binding of integrin α5ß1 promotes its clustering on the host cell surface, triggering activation of focal adhesion kinase (FAK) and cytoskeleton rearrangements to promote bacterial invasion into non-phagocytic cells. Here, we discover that septins, a component of the cytoskeleton that assembles on membranes, are recruited as collar-like structures with actin to S. aureus invasion sites engaging integrin α5ß1. To investigate septin recruitment to the plasma membrane in a bacteria-free system, we used FnBPA-coated latex beads and showed that septins are recruited upon activation of integrin α5ß1. SEPT2 depletion reduced S. aureus invasion, but increased surface expression of integrin α5 and adhesion of S. aureus to host cells. Consistent with this, SEPT2 depletion increased cellular protein levels of integrin α5 and ß1 subunits, as well as FAK. Collectively, these results provide insights into regulation of integrin α5ß1 and invasion of S. aureus by the septin cytoskeleton.


Assuntos
Integrina alfa5beta1 , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Integrina alfa5beta1/metabolismo , Septinas/metabolismo , Integrina alfa5/metabolismo , Fibronectinas , Citoesqueleto/metabolismo
2.
Cytoskeleton (Hoboken) ; 80(7-8): 254-265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35460543

RESUMO

Apoptosis is a form of regulated cell death essential for tissue homeostasis and embryonic development. Apoptosis also plays a key role during bacterial infection, yet some intracellular bacterial pathogens (such as Shigella flexneri, whose lipopolysaccharide can block apoptosis) can manipulate cell death programs as an important survival strategy. Septins are a component of the cytoskeleton essential for mitochondrial dynamics and host defense, however, the role of septins in regulated cell death is mostly unknown. Here, we discover that septins promote mitochondrial (i.e., intrinsic) apoptosis in response to treatment with staurosporine (a pan-kinase inhibitor) or etoposide (a DNA topoisomerase inhibitor). Consistent with a role for septins in mitochondrial dynamics, septins promote the release of mitochondrial protein cytochrome c in apoptotic cells and are required for the proteolytic activation of caspase-3, caspase-7, and caspase-9 (core components of the apoptotic machinery). Apoptosis of HeLa cells induced in response to infection by S. flexneri ΔgalU (a lipopolysaccharide mutant unable to block apoptosis) is also septin-dependent. In vivo, zebrafish larvae are significantly more susceptible to infection with S. flexneri ΔgalU (as compared to infection with wildtype S. flexneri), yet septin deficient larvae are equally susceptible to infection with S. flexneri ΔgalU and wildtype S. flexneri. These data provide a new molecular framework to understand the complexity of mitochondrial apoptosis and its ability to combat bacterial infection.

3.
Cell Microbiol ; 22(4): e13173, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32185906

RESUMO

Investigation of cytoskeleton during bacterial infection has significantly contributed to both cell and infection biology. Bacterial pathogens Listeria monocytogenes and Shigella flexneri are widely recognised as paradigms for investigation of the cytoskeleton during bacterial entry, actin-based motility, and cell-autonomous immunity. At the turn of the century, septins were a poorly understood component of the cytoskeleton mostly studied in the context of yeast cell division and human cancer. In 2002, a screen performed in the laboratory of Pascale Cossart identified septin family member MSF (MLL septin-like fusion, now called SEPT9) associated with L. monocytogenes entry into human epithelial cells. These findings inspired the investigation of septins during L. monocytogenes and S. flexneri infection at the Institut Pasteur, illuminating important roles for septins in host-microbe interactions. In this review, we revisit the history of septin biology and bacterial infection, and discuss how the comparative study of L. monocytogenes and S. flexneri has been instrumental to understand septin roles in cellular homeostasis and host defence.


Assuntos
Infecções Bacterianas/microbiologia , Interações Hospedeiro-Patógeno , Listeria monocytogenes/patogenicidade , Septinas/metabolismo , Shigella flexneri/patogenicidade , Actinas/metabolismo , Autofagia , Divisão Celular , Citoesqueleto , Células Epiteliais/microbiologia , História do Século XX , História do Século XXI , Humanos , Septinas/história
4.
Cell Host Microbe ; 26(6): 823-835.e11, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31761719

RESUMO

RNA-binding proteins (RBPs) perform key cellular activities by controlling the function of bound RNAs. The widely held assumption that RBPs are strictly intracellular has been challenged by the discovery of secreted RBPs. However, extracellular RBPs have been described in eukaryotes, while secreted bacterial RBPs have not been reported. Here, we show that the bacterial pathogen Listeria monocytogenes secretes a small RBP that we named Zea. We show that Zea binds a subset of L. monocytogenes RNAs, causing their accumulation in the extracellular medium. Furthermore, during L. monocytogenes infection, Zea binds RIG-I, the non-self-RNA innate immunity sensor, potentiating interferon-ß production. Mouse infection studies reveal that Zea affects L. monocytogenes virulence. Together, our results unveil that bacterial RNAs can be present extracellularly in association with RBPs, acting as "social RNAs" to trigger a host response during infection.


Assuntos
Proteína DEAD-box 58/metabolismo , Listeria monocytogenes/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Proteína DEAD-box 58/imunologia , Células HEK293 , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Interferon beta/metabolismo , Listeria monocytogenes/imunologia , Listeria monocytogenes/patogenicidade , Camundongos , RNA Bacteriano/metabolismo , Transdução de Sinais/imunologia , Virulência/imunologia
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