Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells
Otitis media (OM) is a group of complex inflammatory disorders affecting the middle ear which can be acute or chronic. Chronic suppurative otitis media (CSOM) is a form of chronic OM characterized by tympanic membrane perforation and discharge. Despite the significant impact of CSOM on human populat...
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| Format: | Online |
| Language: | English |
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Frontiers Media S.A.
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777741/ |
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pubmed-47777412016-03-11 Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells Mittal, Rahul Grati, M’hamed Yan, Denise Liu, Xue Z. Microbiology Otitis media (OM) is a group of complex inflammatory disorders affecting the middle ear which can be acute or chronic. Chronic suppurative otitis media (CSOM) is a form of chronic OM characterized by tympanic membrane perforation and discharge. Despite the significant impact of CSOM on human population, it is still an understudied and unexplored research area. CSOM is a leading cause of hearing loss and life-threatening central nervous system complications. Bacterial exposure especially Pseudomonas aeruginosa is the most common cause of CSOM. Our previous studies have demonstrated that P. aeruginosa invades human middle ear epithelial cells (HMEECs). However, molecular mechanisms leading to bacterial invasion of HMEECs are not known. The aim of this study is to characterize the role of PKC pathway in the ability of P. aeruginosa to colonize HMEECs. We observed that otopathogenic P. aeruginosa activates the PKC pathway, specifically phosphorylation of PKC-alpha (PKC-α) in HMEECs. The ability of otopathogenic P. aeruginosa to phosphorylate PKC-α depends on bacterial OprF expression. The activation of PKC-α was associated with actin condensation. Blocking the PKC pathway attenuated the ability of bacteria to invade HMEECs and subsequent actin condensation. This study, for the first time, demonstrates that the host PKC-α pathway is involved in invasion of HMEECs by P. aeruginosa and subsequently to cause OM. Characterizing the role of the host signaling pathway in the pathogenesis of CSOM will provide novel avenues to design effective treatment modalities against the disease. Frontiers Media S.A. 2016-03-04 /pmc/articles/PMC4777741/ /pubmed/26973629 http://dx.doi.org/10.3389/fmicb.2016.00255 Text en Copyright © 2016 Mittal, Grati, Yan and Liu. 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Mittal, Rahul Grati, M’hamed Yan, Denise Liu, Xue Z. |
| spellingShingle |
Mittal, Rahul Grati, M’hamed Yan, Denise Liu, Xue Z. Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| author_facet |
Mittal, Rahul Grati, M’hamed Yan, Denise Liu, Xue Z. |
| author_sort |
Mittal, Rahul |
| title |
Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| title_short |
Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| title_full |
Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| title_fullStr |
Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| title_full_unstemmed |
Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells |
| title_sort |
pseudomonas aeruginosa activates pkc-alpha to invade middle ear epithelial cells |
| description |
Otitis media (OM) is a group of complex inflammatory disorders affecting the middle ear which can be acute or chronic. Chronic suppurative otitis media (CSOM) is a form of chronic OM characterized by tympanic membrane perforation and discharge. Despite the significant impact of CSOM on human population, it is still an understudied and unexplored research area. CSOM is a leading cause of hearing loss and life-threatening central nervous system complications. Bacterial exposure especially Pseudomonas aeruginosa is the most common cause of CSOM. Our previous studies have demonstrated that P. aeruginosa invades human middle ear epithelial cells (HMEECs). However, molecular mechanisms leading to bacterial invasion of HMEECs are not known. The aim of this study is to characterize the role of PKC pathway in the ability of P. aeruginosa to colonize HMEECs. We observed that otopathogenic P. aeruginosa activates the PKC pathway, specifically phosphorylation of PKC-alpha (PKC-α) in HMEECs. The ability of otopathogenic P. aeruginosa to phosphorylate PKC-α depends on bacterial OprF expression. The activation of PKC-α was associated with actin condensation. Blocking the PKC pathway attenuated the ability of bacteria to invade HMEECs and subsequent actin condensation. This study, for the first time, demonstrates that the host PKC-α pathway is involved in invasion of HMEECs by P. aeruginosa and subsequently to cause OM. Characterizing the role of the host signaling pathway in the pathogenesis of CSOM will provide novel avenues to design effective treatment modalities against the disease. |
| publisher |
Frontiers Media S.A. |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777741/ |
| _version_ |
1613547221944369152 |