title: OtopathogenicPseudomonas aeruginosaEnters and Survives Inside Macrophages.
abstract: Otitis media (OM) is a broad term describing a group of infectious and inflammatory disorders of the middle ear. Despite antibiotic therapy, acute OM can progress to chronic suppurative otitis media (CSOM) characterized by ear drum perforation and purulent discharge.Pseudomonas aeruginosais the most common pathogen associated with CSOM. Although, macrophages play an important role in innate immune responses but their role in the pathogenesis ofP. aeruginosa-induced CSOM is not known. The objective of this study is to examine the interaction ofP. aeruginosawith primary macrophages. We observed thatP. aeruginosaenters and multiplies inside human and mouse primary macrophages. This bacterial entry in macrophages requires both microtubule and actin dependent processes. Transmission electron microscopy demonstrated thatP. aeruginosawas present in membrane bound vesicles inside macrophages. Interestingly, deletion ofoprFexpression inP. aeruginosaabrogates its ability to survive inside macrophages. Our results suggest that otopathogenicP. aeruginosaentry and survival inside macrophages is OprF-dependent. The survival of bacteria inside macrophages will lead to evasion of killing and this lack of pathogen clearance by phagocytes contributes to the persistence of infection in CSOM. Understanding host-pathogen interaction will provide novel avenues to design effective treatment modalities against OM.
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Lisi
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami FL, USA.
authors.forename: Hansi
authors.initials: H
authors.lastname: Kumari
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: M'hamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: Chemistry Department, Center for Advanced Microscopy, University of Miami, Coral GablesFL, USA; Rosenstiel School of Marine and Atmospheric Science, University of Miami, Key BiscayneFL, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Blackwelder
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Jain
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, MiamiFL, USA; Global Health Consortium and Biomolecular Science Institute, Florida International University, MiamiFL, USA.
authors.forename: Kalai
authors.initials: K
authors.lastname: Mathee
authors.affiliation: Health Sciences Department, University of Sagrado Coração Bauru, Brazil.
authors.forename: Paulo H
authors.initials: PH
authors.lastname: Weckwerth
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami FL, USA.
authors.forename: Xue Z
authors.initials: XZ
authors.lastname: Liu
keywords: cell viability; monocyte-derived macrophages; mouse bone marrow-derived macrophages; otopathogenic P. aeruginosa