Correction: A model of chronic, transmissible Otitis Media in mice

Dewan, Kalyan K.; Taylor-Mulneix, Dawn L.; Campos, Laura L.; Skarlupka, Amanda L.; Wagner, Shannon M.; Ryman, Valerie E.; Gestal, Mónica Cartelle; Ma, Longhuan; Blás-Machado, Uriel; Faddis, Brian T.; Harvill, Eric T.

doi:10.1371/journal.ppat.1007916

Cited by 1 publication

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“…This includes the impairment of movement and death of ciliated cells (Perniss et al, 2018). This observation provides an explanation for the progressive hearing loss previously observed in B. pseudohinzii infected mice (Dewan et al, 2019) and could also contribute to bacterial persistence. Additionally, T cells have been implicated in the control and clearance of both upper respiratory and middle ear infections for various Bordetella infections (Leef et al, 2000;Harvill et al, 1999a).…”

Section: Discussionmentioning

confidence: 64%

“…However, these systems do not encompass critical aspects of natural bacterium-host interactions occurring during initial establishment or persistence of middle ear infections and cannot reveal the mechanisms involved in those. B. pseudohinzii has been previously demonstrated to naturally cause middle ear infection in mice that persist for over 3 months, causing chronic otitis media and progressive hearing loss ( Dewan et al., 2019 ). Here, genes particular to B. pseudohinzii and identified as a PTx-like factor, PSx, were investigated and modeling of the catalytic component reveals substantial predicted structural homology to PtxA.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously described the use of Bordetella pseudohinzii , a bacterial species that efficiently colonizes and persists in the middle ears of mice as an experimental model for natural OM progression ( Dewan et al., 2019 ). B. pseudohinzii is a recently described species ( Ivanov et al., 2016 ) that, when introduced in very small numbers to the external nares, naturally and efficiently ascends the Eustachian tube, colonizes, and persists in the middle ears of mice for over three months Dewan et al., 2019 ), apparently for the life of the animal. In addition to its strengths as a model for OM, B. pseudohinzii has also been investigated as an upper respiratory tract pathogen that forms biofilms ( Clark et al., 2016 ) and is cytotoxic to ciliated epithelial cells ( Perniss et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to its strengths as a model for OM, B. pseudohinzii has also been investigated as an upper respiratory tract pathogen that forms biofilms ( Clark et al., 2016 ) and is cytotoxic to ciliated epithelial cells ( Perniss et al., 2018 ). In contrast to B. pseudohinzii , a related species, B. bronchiseptica , can highly efficiently colonize both nasal cavity and middle ears of mice, and persists for life in the noses but is cleared from the middle ears by processes that involve adaptive immunity ( Dewan et al., 2019 ; Dewan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of a Novel Pertussis Toxin-Like Factor in Mediating Persistent Otitis Media

Sedney

et al. 2022

Front. Cell. Infect. Microbiol.

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Chronic otitis media (COM) is the long-term infection and inflammation of the middle ears typically caused by upper respiratory tract pathogens that are able to ascend the Eustachian tube. Our understanding of contributing factors is limited because human otopathogens cannot naturally colonize or persist in the middle ears of mice. We recently described a natural COM in mice caused by Bordetella pseudohinzii and proposed this as an experimental system to study bacterial mechanisms of immune evasion that allow persistent infection of the middle ear. Here we describe a novel pertussis toxin (PTx)-like factor unique to B. pseudohinzii, apparently acquired horizontally, that is associated with its particularly efficient persistence and pathogenesis. The catalytic subunit of this toxin, PsxA, has conserved catalytic sites and substantial predicted structural homology to pertussis toxin catalytic subunit PtxA. Deletion of the gene predicted to encode the catalytic subunit, psxA, resulted in a significant decrease in persistence in the middle ears. The defect was not observed in mice lacking T cells, indicating that PsxA is necessary for persistence only when T cells are present. These results demonstrate the role of a novel putative toxin in the persistence of B. pseudohinzii and its generation of COM. This PsxA-mediated immune evasion strategy may similarly be utilized by human otopathogens, via other PTx-like toxins or alternative mechanisms to disrupt critical T cell functions necessary to clear bacteria from the middle ear. This work demonstrates that this experimental system can allow for the detailed study of general strategies and specific mechanisms that otopathogens use to evade host immune responses to persist in the middle ear to cause COM.

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