title: Sialic acid: a preventable signal for pneumococcal biofilm formation, colonization, and invasion of the host.
abstract: The correlation between carbohydrate availability, pneumococcal biofilm formation, nasopharyngeal colonization, and invasion of the host has been investigated. Of a series of sugars, only sialic acid (i.e., N-acetylneuraminic acid) enhanced pneumococcal biofilm formation in vitro, at concentrations similar to those of free sialic acid in human saliva. In a murine model of pneumococcal carriage, intranasal inoculation of sialic acid significantly increased pneumococcal counts in the nasopharynx and instigated translocation of pneumococci to the lungs. Competition of both sialic acid-dependent phenotypes was found to be successful when evaluated using the neuraminidase inhibitors DANA (i.e., 2,3-didehydro-2-deoxy-N-acetylneuraminic acid), zanamivir, and oseltamivir. The association between levels of free sialic acid on mucosae, pneumococcal colonization, and development of invasive disease shows how a host-derived molecule can influence a colonizing microbe and also highlights a molecular mechanism that explains the epidemiologic correlation between respiratory infections due to neuraminidase-bearing viruses and bacterial pneumonia. The data provide a new paradigm for the role of a host compound in infectious diseases and point to new treatment strategies.
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena , Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Trappetti
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: Melissa
authors.initials: M
authors.lastname: Carter
authors.forename: Jasvinder
authors.initials: J
authors.lastname: Hayre
authors.forename: Francesco
authors.initials: F
authors.lastname: Iannelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D017931:DNA Primers; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011008:Pneumococcal Infections / Q000175:diagnosis* / Q000635:transmission; D012463:Saliva / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D053243:Zanamivir / Q000494:pharmacology
chemical_list: D017931:DNA Primers; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D053243:Zanamivir