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The Haemophilus influenzae Sap transporter mediates bacterium-epithelial cell homeostasis.
- Source :
-
Infection and immunity [Infect Immun] 2013 Jan; Vol. 81 (1), pp. 43-54. Date of Electronic Publication: 2012 Oct 15. - Publication Year :
- 2013
-
Abstract
- Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharynx and a causative agent of otitis media and other diseases of the upper and lower human airway. During colonization within the host, NTHI must acquire essential nutrients and evade immune attack. We previously demonstrated that the NTHI Sap transporter, an inner membrane protein complex, mediates resistance to antimicrobial peptides and is required for heme homeostasis. We hypothesized that Sap transporter functions are critical for NTHI interaction with the host epithelium and establishment of colonization. Thus, we cocultured the parent or the sapA mutant on polarized epithelial cells grown at an air-liquid interface, as a physiological model of NTHI colonization, to determine the contribution of the Sap transporter to bacterium-host cell interactions. Although SapA-deficient NTHI was less adherent to epithelial cells, we observed a significant increase in invasive bacteria compared to the parent strain. Upon internalization, the sapA mutant appeared free in the cytoplasm, whereas the parent strain was primarily found in endosomes, indicating differential subcellular trafficking. Additionally, we observed reduced inflammatory cytokine production by the epithelium in response to the sapA mutant strain compared to the parental strain. Furthermore, chinchilla middle ears challenged with the sapA mutant demonstrated a decrease in disease severity compared to ears challenged with the parental strain. Collectively, our data suggest that NTHI senses host environmental cues via Sap transporter function to mediate interaction with host epithelial cells. Epithelial cell invasion and modulation of host inflammatory cytokine responses may promote NTHI colonization and access to essential nutrients.
- Subjects :
- Animals
Bacterial Proteins immunology
Cell Adhesion immunology
Cell Line
Cell Line, Tumor
Chinchilla
Cytokines immunology
Cytokines metabolism
Cytoplasm immunology
Cytoplasm microbiology
Ear, Middle immunology
Ear, Middle metabolism
Ear, Middle microbiology
Epithelial Cells immunology
Epithelial Cells metabolism
Haemophilus Infections immunology
Haemophilus influenzae immunology
Homeostasis immunology
Humans
Membrane Transport Proteins immunology
Mutation immunology
Otitis Media immunology
Otitis Media metabolism
Otitis Media microbiology
Bacterial Proteins metabolism
Epithelial Cells microbiology
Haemophilus Infections metabolism
Haemophilus influenzae metabolism
Host-Pathogen Interactions immunology
Membrane Transport Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 81
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 23071138
- Full Text :
- https://doi.org/10.1128/IAI.00942-12