title: Direct evaluation of Pseudomonas aeruginosa biofilm mediators in a chronic infection model.
abstract: Biofilms contribute to Pseudomonas aeruginosa persistence in a variety of diseases, including cystic fibrosis, burn wounds, and chronic suppurative otitis media. However, few studies have directly addressed P. aeruginosa biofilms in vivo. We used a chinchilla model of otitis media, which has previously been used to study persistent Streptococcus pneumoniae and Haemophilus influenzae infections, to show that structures formed in vivo are biofilms of bacterial and host origin within a matrix that includes Psl, a P. aeruginosa biofilm polysaccharide. We evaluated three biofilm and/or virulence mediators of P. aeruginosa known to affect biofilm formation in vitro and pathogenesis in vivo--bis-(3',5')-cyclic dimeric GMP (c-di-GMP), flagella, and quorum sensing--in a chinchilla model. We show that c-di-GMP overproduction has a positive impact on bacterial persistence, while quorum sensing increases virulence. We found no difference in persistence attributed to flagella. We conclude from these studies that a chinchilla otitis media model provides a means to evaluate pathogenic mediators of P. aeruginosa and that in vitro phenotypes should be examined in multiple infection systems to fully understand their role in disease.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Byrd
authors.forename: Bing
authors.initials: B
authors.lastname: Pang
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Hong
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Waligora
authors.forename: Richard A
authors.initials: RA
authors.lastname: Juneau
authors.forename: Chelsie E
authors.initials: CE
authors.lastname: Armbruster
authors.forename: Kristen E D
authors.initials: KE
authors.lastname: Weimer
authors.forename: Kyle
authors.initials: K
authors.lastname: Murrah
authors.forename: Ethan E
authors.initials: EE
authors.lastname: Mann
authors.forename: Haiping
authors.initials: H
authors.lastname: Lu
authors.forename: April
authors.initials: A
authors.lastname: Sprinkle
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Parsek
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Kock
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wozniak
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D002682:Chinchilla; D002908:Chronic Disease; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D010033:Otitis Media / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*; D053038:Quorum Sensing; D012376:Rodent Diseases / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP