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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011388 |
| _version_ | 1797818549968830464 |
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| author | Manisha Naskar Viraj P Parekh Mathew A Abraham Zehra Alibasic Min Jung Kim Gyeongseo Suk Joo Hwan Noh Kwan Young Ko Joonha Lee Chungho Kim Hana Yoon Soman N Abraham Hae Woong Choi |
| author_facet | Manisha Naskar Viraj P Parekh Mathew A Abraham Zehra Alibasic Min Jung Kim Gyeongseo Suk Joo Hwan Noh Kwan Young Ko Joonha Lee Chungho Kim Hana Yoon Soman N Abraham Hae Woong Choi |
| author_sort | Manisha Naskar |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-13T09:09:31Z |
| format | Article |
| id | doaj.art-17393b6872954c6b93e5eef1fedde341 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T09:09:31Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-17393b6872954c6b93e5eef1fedde3412023-05-27T05:31:04ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101138810.1371/journal.ppat.1011388α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification.Manisha NaskarViraj P ParekhMathew A AbrahamZehra AlibasicMin Jung KimGyeongseo SukJoo Hwan NohKwan Young KoJoonha LeeChungho KimHana YoonSoman N AbrahamHae Woong ChoiThere 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.https://doi.org/10.1371/journal.ppat.1011388 |
| spellingShingle | Manisha Naskar Viraj P Parekh Mathew A Abraham Zehra Alibasic Min Jung Kim Gyeongseo Suk Joo Hwan Noh Kwan Young Ko Joonha Lee Chungho Kim Hana Yoon Soman N Abraham Hae Woong Choi α-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1011388 |
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