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: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-03-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00255/full |
| _version_ | 1819161247274237952 |
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| author | Rahul eMittal M'hamed eGrati Denise eYan Xue eLiu |
| author_facet | Rahul eMittal M'hamed eGrati Denise eYan Xue eLiu |
| author_sort | Rahul eMittal |
| collection | DOAJ |
| 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) as compared to other isoforms for which bacterial OprF expression is required. This 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 HMECCs 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. |
| first_indexed | 2024-12-22T17:09:18Z |
| format | Article |
| id | doaj.art-c0a1deb325674fc188edc300e9056ae0 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T17:09:18Z |
| publishDate | 2016-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-c0a1deb325674fc188edc300e9056ae02022-12-21T18:19:06ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-03-01710.3389/fmicb.2016.00255184401Pseudomonas aeruginosa activates PKC-alpha to invade middle ear epithelial cells.Rahul eMittal0M'hamed eGrati1Denise eYan2Xue eLiu3University of MiamiUniversity of MiamiUniversity of MiamiUniversity of MiamiOtitis 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) as compared to other isoforms for which bacterial OprF expression is required. This 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 HMECCs 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00255/fullPseudomonas aeruginosaMARCKSChronic suppurative otitis mediaPKC pathwayPepTag assay |
| spellingShingle | Rahul eMittal M'hamed eGrati Denise eYan Xue eLiu Pseudomonas aeruginosa activates PKC-alpha to invade middle ear epithelial cells. Frontiers in Microbiology Pseudomonas aeruginosa MARCKS Chronic suppurative otitis media PKC pathway PepTag assay |
| title | 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_short | Pseudomonas aeruginosa activates PKC-alpha to invade middle ear epithelial cells. |
| title_sort | pseudomonas aeruginosa activates pkc alpha to invade middle ear epithelial cells |
| topic | Pseudomonas aeruginosa MARCKS Chronic suppurative otitis media PKC pathway PepTag assay |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00255/full |
| work_keys_str_mv | AT rahulemittal pseudomonasaeruginosaactivatespkcalphatoinvademiddleearepithelialcells AT mhamedegrati pseudomonasaeruginosaactivatespkcalphatoinvademiddleearepithelialcells AT deniseeyan pseudomonasaeruginosaactivatespkcalphatoinvademiddleearepithelialcells AT xueeliu pseudomonasaeruginosaactivatespkcalphatoinvademiddleearepithelialcells |