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α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification

There is a growing consensus that a significant proportion of recurrent urinary tract infections are linked to the persistence of uropathogens within the urinary tract and their re-emergence upon the conclusion of antibiotic treatment. Studies in mice and human have revealed that uropathogenic Esche...

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Autores principales: Naskar, Manisha, Parekh, Viraj P., Abraham, Mathew A., Alibasic, Zehra, Kim, Min Jung, Suk, Gyeongseo, Noh, Joo Hwan, Ko, Kwan Young, Lee, Joonha, Kim, Chungho, Yoon, Hana, Abraham, Soman N., Choi, Hae Woong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204954/
https://www.ncbi.nlm.nih.gov/pubmed/37167325
http://dx.doi.org/10.1371/journal.ppat.1011388
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author Naskar, Manisha
Parekh, Viraj P.
Abraham, Mathew A.
Alibasic, Zehra
Kim, Min Jung
Suk, Gyeongseo
Noh, Joo Hwan
Ko, Kwan Young
Lee, Joonha
Kim, Chungho
Yoon, Hana
Abraham, Soman N.
Choi, Hae Woong
author_facet Naskar, Manisha
Parekh, Viraj P.
Abraham, Mathew A.
Alibasic, Zehra
Kim, Min Jung
Suk, Gyeongseo
Noh, Joo Hwan
Ko, Kwan Young
Lee, Joonha
Kim, Chungho
Yoon, Hana
Abraham, Soman N.
Choi, Hae Woong
author_sort Naskar, Manisha
collection PubMed
description There is a growing consensus that a significant proportion of recurrent urinary tract infections are linked to the persistence of uropathogens within the urinary tract and their re-emergence upon the conclusion of antibiotic treatment. Studies in mice and human have revealed that uropathogenic Escherichia coli (UPEC) can persist in bladder epithelial cells (BECs) even after the apparent resolution of the infection. Here, we found that, following the entry of UPEC into RAB27b(+) fusiform vesicles in BECs, some bacteria escaped into the cytoplasmic compartment via a mechanism involving hemolysin A (HlyA). However, these UPEC were immediately recaptured within LC3A/B(+) autophagosomes that matured into LAMP1(+) autolysosomes. Thereafter, HlyA(+) UPEC-containing lysosomes failed to acidify, which is an essential step for bacterial elimination. This lack of acidification was related to the inability of bacteria-harboring compartments to recruit V-ATPase proton pumps, which was attributed to the defragmentation of cytosolic microtubules by HlyA. The persistence of UPEC within LAMP1(+) compartments in BECs appears to be directly linked to HlyA. Thus, through intravesicular instillation of microtubule stabilizer, this host defense response can be co-opted to reduce intracellular bacterial burden following UTIs in the bladder potentially preventing recurrence.
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spelling pubmed-102049542023-05-24 α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification Naskar, Manisha Parekh, Viraj P. Abraham, Mathew A. Alibasic, Zehra Kim, Min Jung Suk, Gyeongseo Noh, Joo Hwan Ko, Kwan Young Lee, Joonha Kim, Chungho Yoon, Hana Abraham, Soman N. Choi, Hae Woong PLoS Pathog Research Article There is a growing consensus that a significant proportion of recurrent urinary tract infections are linked to the persistence of uropathogens within the urinary tract and their re-emergence upon the conclusion of antibiotic treatment. Studies in mice and human have revealed that uropathogenic Escherichia coli (UPEC) can persist in bladder epithelial cells (BECs) even after the apparent resolution of the infection. Here, we found that, following the entry of UPEC into RAB27b(+) fusiform vesicles in BECs, some bacteria escaped into the cytoplasmic compartment via a mechanism involving hemolysin A (HlyA). However, these UPEC were immediately recaptured within LC3A/B(+) autophagosomes that matured into LAMP1(+) autolysosomes. Thereafter, HlyA(+) UPEC-containing lysosomes failed to acidify, which is an essential step for bacterial elimination. This lack of acidification was related to the inability of bacteria-harboring compartments to recruit V-ATPase proton pumps, which was attributed to the defragmentation of cytosolic microtubules by HlyA. The persistence of UPEC within LAMP1(+) compartments in BECs appears to be directly linked to HlyA. Thus, through intravesicular instillation of microtubule stabilizer, this host defense response can be co-opted to reduce intracellular bacterial burden following UTIs in the bladder potentially preventing recurrence. Public Library of Science 2023-05-11 /pmc/articles/PMC10204954/ /pubmed/37167325 http://dx.doi.org/10.1371/journal.ppat.1011388 Text en © 2023 Naskar 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
Naskar, Manisha
Parekh, Viraj P.
Abraham, Mathew A.
Alibasic, Zehra
Kim, Min Jung
Suk, Gyeongseo
Noh, Joo Hwan
Ko, Kwan Young
Lee, Joonha
Kim, Chungho
Yoon, Hana
Abraham, Soman N.
Choi, Hae Woong
α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title_full α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title_fullStr α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title_full_unstemmed α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title_short α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
title_sort α-hemolysin promotes uropathogenic e. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204954/
https://www.ncbi.nlm.nih.gov/pubmed/37167325
http://dx.doi.org/10.1371/journal.ppat.1011388
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