title: Catecholamine norepinephrine diminishes lung epithelial cell adhesion of Streptococcus pneumoniae by binding iron.
abstract: Systemic release of norepinephrine (NE) is a component of the acute host response to infection, and studies in the field of microbial endocrinology indicate generally that NE increases the bacterial growth rate and promotes invasive disease. However, NE attenuates experimental invasive pneumococcal disease. We determined that NE promoted pneumococcal growth but paradoxically decreased pneumococcal adhesion to host cells. This effect was independent of the classical adhesin CbpA. Microarray analysis indicated that the effect of NE involved two two-component regulatory systems that both regulate expression of the Piu iron uptake ABC transport operon. We propose that NE, a known siderophore, enhances iron availability to the bacteria, resulting in greater bacterial replication and decreased expression of Piu operon products. Downregulation of the operon includes decreased expression of the Piu-associated adhesin PiuD. Our results suggested that the iron-dependent inhibitory effect of NE on pneumococcal adherence is a mechanism underlying the amelioration of pneumococcal disease by NE.
authors: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico.
authors: Xavier F
authors: XF
authors: Gonzales
authors: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico.
authors: Gonzalo
authors: G
authors: Castillo-Rojas
authors: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico.
authors: Antonia I
authors: AI
authors: Castillo-Rodal
authors: Department of Infectious Diseases, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors: Elaine
authors: E
authors: Tuomanen
authors: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City, CP 04510, Mexico.
authors: Yolanda
authors: Y
authors: López-Vidal
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D004847:Epithelial Cells / Q000382:microbiology*; D020869:Gene Expression Profiling; D007501:Iron / Q000378:metabolism*; D046228:Microarray Analysis; D009638:Norepinephrine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*
chemical_list: D007501:Iron; D009638:Norepinephrine