Sialic acid: a preventable signal for pneumococcal biofilm formation, colonization, and invasion of the host.
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.
Trappetti
Claudia
C
Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena , Siena, Italy.
Kadioglu
Aras
A
Carter
Melissa
M
Hayre
Jasvinder
J
Iannelli
Francesco
F
Pozzi
Gianni
G
Andrew
Peter W
PW
Oggioni
Marco R
MR
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
D017931:DNA Primers; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D053243:Zanamivir