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Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pa...

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Autores principales: Sycz, Gabriela, Di Venanzio, Gisela, Distel, Jesus S., Sartorio, Mariana G., Le, Nguyen-Hung, Scott, Nichollas E., Beatty, Wandy L., Feldman, Mario F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376066/
https://www.ncbi.nlm.nih.gov/pubmed/34370792
http://dx.doi.org/10.1371/journal.ppat.1009802
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author Sycz, Gabriela
Di Venanzio, Gisela
Distel, Jesus S.
Sartorio, Mariana G.
Le, Nguyen-Hung
Scott, Nichollas E.
Beatty, Wandy L.
Feldman, Mario F.
author_facet Sycz, Gabriela
Di Venanzio, Gisela
Distel, Jesus S.
Sartorio, Mariana G.
Le, Nguyen-Hung
Scott, Nichollas E.
Beatty, Wandy L.
Feldman, Mario F.
author_sort Sycz, Gabriela
collection PubMed
description Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication of A. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance of A. baumannii.
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spelling pubmed-83760662021-08-20 Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages Sycz, Gabriela Di Venanzio, Gisela Distel, Jesus S. Sartorio, Mariana G. Le, Nguyen-Hung Scott, Nichollas E. Beatty, Wandy L. Feldman, Mario F. PLoS Pathog Research Article Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium’s pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication of A. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance of A. baumannii. Public Library of Science 2021-08-09 /pmc/articles/PMC8376066/ /pubmed/34370792 http://dx.doi.org/10.1371/journal.ppat.1009802 Text en © 2021 Sycz et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sycz, Gabriela
Di Venanzio, Gisela
Distel, Jesus S.
Sartorio, Mariana G.
Le, Nguyen-Hung
Scott, Nichollas E.
Beatty, Wandy L.
Feldman, Mario F.
Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title_full Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title_fullStr Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title_full_unstemmed Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title_short Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
title_sort modern acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376066/
https://www.ncbi.nlm.nih.gov/pubmed/34370792
http://dx.doi.org/10.1371/journal.ppat.1009802
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