You are here: Home Published Research The Haemophilus Sap Transporter Mediates Bacterial-Epithelial Cell Homeostasis.

Forrest K Raffel, Blake R Szelestey, Wandy L Beatty, and Kevin M Mason (2012)

The Haemophilus Sap Transporter Mediates Bacterial-Epithelial Cell Homeostasis.

Infection and immunity.

Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharynx, and 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 co-cultured 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 on bacterial-host cell interactions. Although SapA-deficient NTHI were 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 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 sense 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.

 
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