title: Novel therapies for the treatment of pertussis disease.
abstract: Whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. Previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. Early diagnosis is complicated by the non-diagnostic presentation of disease early in infection. This review focuses on previous attempts at developing novel host-directed therapies for the treatment of pertussis. In addition, two novel approaches from our group are discussed. Manipulation of the signaling pathway of sphingosine-1-phosphate, a lipid involved in many immune processes, has shown great promise, but is in its infancy. Pendrin, a host epithelial anion exchanger upregulated in the airways with B. pertussis infection, appears to drive mucus production and dysregulation of airway surface liquid pH and salinity. In addition to detailing these potential new therapeutic targets, the need for greater focus on the neonatal model of disease is highlighted.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, MD 21201, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Scanlon
authors.affiliation: Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, MD 21201, USA.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Skerry
authors.affiliation: Department of Microbiology and Immunology, University of Maryland Medical School, Baltimore, MD 21201, USA ncarbonetti@som.umaryland.edu.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Carbonetti
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000639:trends; D004358:Drug Therapy / Q000379:methods*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D008246:Lysophospholipids / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D000076988:Sulfate Transporters; D014917:Whooping Cough / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D008246:Lysophospholipids; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: ECMO; acetazolamide; leucocytosis; pendrin; respiratory disease; sphingosine-1-phosphate