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The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis

Francisella tularensis is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unkn...

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Autores principales: Schmitt, Deanna M., Barnes, Rebecca, Rogerson, Taylor, Haught, Ashley, Mazzella, Leanne K., Ford, Matthew, Gilson, Tricia, Birch, James W.-M., Sjöstedt, Anders, Reed, Douglas S., Franks, Jonathan M., Stolz, Donna B., Denvir, James, Fan, Jun, Rekulapally, Swanthana, Primerano, Donald A., Horzempa, Joseph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423315/
https://www.ncbi.nlm.nih.gov/pubmed/28536678
http://dx.doi.org/10.3389/fcimb.2017.00173
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author Schmitt, Deanna M.
Barnes, Rebecca
Rogerson, Taylor
Haught, Ashley
Mazzella, Leanne K.
Ford, Matthew
Gilson, Tricia
Birch, James W.-M.
Sjöstedt, Anders
Reed, Douglas S.
Franks, Jonathan M.
Stolz, Donna B.
Denvir, James
Fan, Jun
Rekulapally, Swanthana
Primerano, Donald A.
Horzempa, Joseph
author_facet Schmitt, Deanna M.
Barnes, Rebecca
Rogerson, Taylor
Haught, Ashley
Mazzella, Leanne K.
Ford, Matthew
Gilson, Tricia
Birch, James W.-M.
Sjöstedt, Anders
Reed, Douglas S.
Franks, Jonathan M.
Stolz, Donna B.
Denvir, James
Fan, Jun
Rekulapally, Swanthana
Primerano, Donald A.
Horzempa, Joseph
author_sort Schmitt, Deanna M.
collection PubMed
description Francisella tularensis is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unknown how F. tularensis invades these cells. Furthermore, the consequence of inhabiting the intracellular space of red blood cells (RBCs) has not been determined. Here, we provide evidence indicating that residing within an erythrocyte enhances the ability of F. tularensis to colonize ticks following a blood meal. Erythrocyte residence protected F. tularensis from a low pH environment similar to that of gut cells of a feeding tick. Mechanistic studies revealed that the F. tularensis type VI secretion system (T6SS) was required for erythrocyte invasion as mutation of mglA (a transcriptional regulator of T6SS genes), dotU, or iglC (two genes encoding T6SS machinery) severely diminished bacterial entry into RBCs. Invasion was also inhibited upon treatment of erythrocytes with venom from the Blue-bellied black snake (Pseudechis guttatus), which aggregates spectrin in the cytoskeleton, but not inhibitors of actin polymerization and depolymerization. These data suggest that erythrocyte invasion by F. tularensis is dependent on spectrin utilization which is likely mediated by effectors delivered through the T6SS. Our results begin to elucidate the mechanism of a unique biological process facilitated by F. tularensis to invade erythrocytes, allowing for enhanced colonization of ticks.
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spelling pubmed-54233152017-05-23 The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis Schmitt, Deanna M. Barnes, Rebecca Rogerson, Taylor Haught, Ashley Mazzella, Leanne K. Ford, Matthew Gilson, Tricia Birch, James W.-M. Sjöstedt, Anders Reed, Douglas S. Franks, Jonathan M. Stolz, Donna B. Denvir, James Fan, Jun Rekulapally, Swanthana Primerano, Donald A. Horzempa, Joseph Front Cell Infect Microbiol Microbiology Francisella tularensis is an extremely virulent bacterium that can be transmitted naturally by blood sucking arthropods. During mammalian infection, F. tularensis infects numerous types of host cells, including erythrocytes. As erythrocytes do not undergo phagocytosis or endocytosis, it remains unknown how F. tularensis invades these cells. Furthermore, the consequence of inhabiting the intracellular space of red blood cells (RBCs) has not been determined. Here, we provide evidence indicating that residing within an erythrocyte enhances the ability of F. tularensis to colonize ticks following a blood meal. Erythrocyte residence protected F. tularensis from a low pH environment similar to that of gut cells of a feeding tick. Mechanistic studies revealed that the F. tularensis type VI secretion system (T6SS) was required for erythrocyte invasion as mutation of mglA (a transcriptional regulator of T6SS genes), dotU, or iglC (two genes encoding T6SS machinery) severely diminished bacterial entry into RBCs. Invasion was also inhibited upon treatment of erythrocytes with venom from the Blue-bellied black snake (Pseudechis guttatus), which aggregates spectrin in the cytoskeleton, but not inhibitors of actin polymerization and depolymerization. These data suggest that erythrocyte invasion by F. tularensis is dependent on spectrin utilization which is likely mediated by effectors delivered through the T6SS. Our results begin to elucidate the mechanism of a unique biological process facilitated by F. tularensis to invade erythrocytes, allowing for enhanced colonization of ticks. Frontiers Media S.A. 2017-05-09 /pmc/articles/PMC5423315/ /pubmed/28536678 http://dx.doi.org/10.3389/fcimb.2017.00173 Text en Copyright © 2017 Schmitt, Barnes, Rogerson, Haught, Mazzella, Ford, Gilson, Birch, Sjöstedt, Reed, Franks, Stolz, Denvir, Fan, Rekulapally, Primerano and Horzempa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Schmitt, Deanna M.
Barnes, Rebecca
Rogerson, Taylor
Haught, Ashley
Mazzella, Leanne K.
Ford, Matthew
Gilson, Tricia
Birch, James W.-M.
Sjöstedt, Anders
Reed, Douglas S.
Franks, Jonathan M.
Stolz, Donna B.
Denvir, James
Fan, Jun
Rekulapally, Swanthana
Primerano, Donald A.
Horzempa, Joseph
The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title_full The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title_fullStr The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title_full_unstemmed The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title_short The Role and Mechanism of Erythrocyte Invasion by Francisella tularensis
title_sort role and mechanism of erythrocyte invasion by francisella tularensis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423315/
https://www.ncbi.nlm.nih.gov/pubmed/28536678
http://dx.doi.org/10.3389/fcimb.2017.00173
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