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SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus

Non-typeable Haemophilus influenzae (NTHI) is a common commensal bacterium that resides in the human upper respiratory tract of healthy individuals. NTHI is also a known causative agent of multiple diseases including sinusitis, otitis media, as well as exacerbates disease severity of patients with c...

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Autores principales: Vogel, Andrew R., Szelestey, Blake R., Raffel, Forrest K., Sharpe, Samantha W., Gearinger, Rachel L., Justice, Sheryl S., Mason, Kevin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417626/
https://www.ncbi.nlm.nih.gov/pubmed/22919633
http://dx.doi.org/10.3389/fcimb.2012.00042
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author Vogel, Andrew R.
Szelestey, Blake R.
Raffel, Forrest K.
Sharpe, Samantha W.
Gearinger, Rachel L.
Justice, Sheryl S.
Mason, Kevin M.
author_facet Vogel, Andrew R.
Szelestey, Blake R.
Raffel, Forrest K.
Sharpe, Samantha W.
Gearinger, Rachel L.
Justice, Sheryl S.
Mason, Kevin M.
author_sort Vogel, Andrew R.
collection PubMed
description Non-typeable Haemophilus influenzae (NTHI) is a common commensal bacterium that resides in the human upper respiratory tract of healthy individuals. NTHI is also a known causative agent of multiple diseases including sinusitis, otitis media, as well as exacerbates disease severity of patients with cystic fibrosis and chronic obstructive pulmonary disease. We have previously shown that the Sap transporter mediates resistance to host antimicrobial peptides (AMPs) and import of the iron-containing compound heme. Here, we analyzed the contribution of the Sap structural ATPase protein, SapF, in these essential functions. In contrast to SapD, SapF was dispensable for NTHI survival when exposed to AMPs in vitro. SapF was responsible for heme utilization and recovery of depleted internal heme-iron stores. Further, a loss of SapF resulted in morphological plasticity and enhanced community development and biofilm architecture, suggesting the potential role of heme-iron availability in coordinating the complexity of NTHI biofilm architecture. SapF was required for colonization of the nasopharynx and acute infection of the middle ear, as SapF deficiency correlated with a statistically significant decrease in NTHI persistence in vivo. These data suggest that SapF is required for proper heme utilization which directly impacts NTHI survival. Thus, these studies further support a role for the Sap complex in the transport of multiple substrates and further defines substrate specificity for the two ATPase subunits. Given the multiple essential functions provided by the Sap transporter, this complex could prove to be an effective therapeutic target for the treatment of NTHI diseases.
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spelling pubmed-34176262012-08-23 SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus Vogel, Andrew R. Szelestey, Blake R. Raffel, Forrest K. Sharpe, Samantha W. Gearinger, Rachel L. Justice, Sheryl S. Mason, Kevin M. Front Cell Infect Microbiol Microbiology Non-typeable Haemophilus influenzae (NTHI) is a common commensal bacterium that resides in the human upper respiratory tract of healthy individuals. NTHI is also a known causative agent of multiple diseases including sinusitis, otitis media, as well as exacerbates disease severity of patients with cystic fibrosis and chronic obstructive pulmonary disease. We have previously shown that the Sap transporter mediates resistance to host antimicrobial peptides (AMPs) and import of the iron-containing compound heme. Here, we analyzed the contribution of the Sap structural ATPase protein, SapF, in these essential functions. In contrast to SapD, SapF was dispensable for NTHI survival when exposed to AMPs in vitro. SapF was responsible for heme utilization and recovery of depleted internal heme-iron stores. Further, a loss of SapF resulted in morphological plasticity and enhanced community development and biofilm architecture, suggesting the potential role of heme-iron availability in coordinating the complexity of NTHI biofilm architecture. SapF was required for colonization of the nasopharynx and acute infection of the middle ear, as SapF deficiency correlated with a statistically significant decrease in NTHI persistence in vivo. These data suggest that SapF is required for proper heme utilization which directly impacts NTHI survival. Thus, these studies further support a role for the Sap complex in the transport of multiple substrates and further defines substrate specificity for the two ATPase subunits. Given the multiple essential functions provided by the Sap transporter, this complex could prove to be an effective therapeutic target for the treatment of NTHI diseases. Frontiers Media S.A. 2012-04-03 /pmc/articles/PMC3417626/ /pubmed/22919633 http://dx.doi.org/10.3389/fcimb.2012.00042 Text en Copyright © 2012 Vogel, Szelestey, Raffel, Sharpe, Gearinger, Justice and Mason. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Microbiology
Vogel, Andrew R.
Szelestey, Blake R.
Raffel, Forrest K.
Sharpe, Samantha W.
Gearinger, Rachel L.
Justice, Sheryl S.
Mason, Kevin M.
SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title_full SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title_fullStr SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title_full_unstemmed SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title_short SapF-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of Haemophilus
title_sort sapf-mediated heme-iron utilization enhances persistence and coordinates biofilm architecture of haemophilus
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417626/
https://www.ncbi.nlm.nih.gov/pubmed/22919633
http://dx.doi.org/10.3389/fcimb.2012.00042
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