ArticleJournal of bacteriology2011
Heme utilization by nontypeable Haemophilus influenzae is essential and dependent on Sap transporter function.
Article in Journal of bacteriology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- A novelVirulence · 2025Article
- Structurally diverse C-terminal accessory domains in type I ABC importers reveal distinct regulatory mechanisms.Structure (London, England : 1993) · 2025Review
- Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025Review
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- AInfection and immunity · 2024Article
- Antimicrobial Peptide Recognition Motif of the Substrate Binding Protein SapA from NontypeableBiochemistry · 2024Article
- Article
- Gene essentiality profiling reveals a novel determinant of stresses preventing protein aggregation inEmerging microbes & infections · 2022Article
- The role of bacterial transport systems in the removal of host antimicrobial peptides in Gram-negative bacteria.FEMS microbiology reviews · 2022Review
- Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities.Biophysical reviews · 2021Review
- Article
- In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains ofPathogens (Basel, Switzerland) · 2020Article
- Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner.Virulence · 2019Article
- A Novel Role for the Klebsiella pneumoniae Sap (Sensitivity to Antimicrobial Peptides) Transporter in Intestinal Cell Interactions, Innate Immune Responses, Liver Abscess, and Virulence.The Journal of infectious diseases · 2019Article
- Oligopeptide-binding protein from nontypeableThe Journal of biological chemistry · 2019Article
- The Capsule Regulatory Network ofmBio · 2018Article
- Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence.PLoS pathogens · 2018Article
- Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development.mSphere · 2018Article
- Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection.Physiological reviews · 2018Review
- Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis.Biochimica et biophysica acta. Biomembranes · 2018Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Bacterial strategies of innate immune evasion and essential metabolic functions are critical for commensal-host homeostasis. Previously, we showed that Sap translocator function is necessary for nontypeable Haemophilus influenzae (NTHI) behaviors that mediate diseases of the human airway. Antimicrobial peptide (AP) lethality is limited by binding mediated by the Sap complex. SapA shares homology with the dipeptide-binding protein (DppA) and the heme-binding lipoprotein (HbpA), both of which have previously been shown to bind the iron-containing compound heme, whose acquisition is essential for Haemophilus survival. Computational modeling revealed conserved SapA residues, similarly modeled to mediate heme binding in HbpA. Here, we directly demonstrate that SapA bound heme and was essential for heme utilization by iron-starved NTHI. Further, the Sap translocator permease mediated heme transport into the bacterial cytoplasm, thus defining a heretofore unknown mechanism of intracytoplasmic membrane heme transport in Haemophilus. Since we demonstrate multiple ligand specificity for the SapA-binding protein, we tested whether APs would compete with heme for SapA binding. We showed that human β-defensins 2 and 3, human cathelicidin LL-37, human neutrophil protein 1, and melittin displaced heme bound to SapA, thus supporting a hierarchy wherein immune evasion supercedes even the needed iron acquisition functions of the Sap system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.