title: Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo.
abstract: Otitis media (OM) is an extremely common pediatric ailment caused by opportunists that reside within the nasopharynx. Inflammation within the upper airway can promote ascension of these opportunists into the middle ear chamber. OM can be chronic/recurrent in nature, and a wealth of data indicates that in these cases, the bacteria persist within biofilms. Epidemiological data demonstrate that most cases of OM are polymicrobial, which may have significant impact on antibiotic resistance. In this study, we used in vitro biofilm assays and rodent infection models to examine the impact of polymicrobial infection with Moraxella catarrhalis and Streptococcus pneumoniae (pneumococcus) on biofilm resistance to antibiotic treatment and persistence in vivo. Consistent with prior work, M. catarrhalis conferred beta-lactamase-dependent passive protection from beta-lactam killing to pneumococci within polymicrobial biofilms. Moreover, pneumococci increased resistance of M. catarrhalis to macrolide killing in polymicrobial biofilms. However, pneumococci increased colonization in vivo by M. catarrhalis in a quorum signal-dependent manner. We also found that co-infection with M. catarrhalis affects middle ear ascension of pneumococci in both mice and chinchillas. Therefore, we conclude that residence of M. catarrhalis and pneumococci within the same biofilm community significantly impacts resistance to antibiotic treatment and bacterial persistence in vivo.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Antonia C
authors.initials: AC
authors.lastname: Perez
authors.forename: Bing
authors.initials: B
authors.lastname: Pang
authors.forename: Lauren B
authors.initials: LB
authors.lastname: King
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Murrah
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reimche
authors.forename: John T
authors.initials: JT
authors.lastname: Wren
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Richardson
authors.forename: Uma
authors.initials: U
authors.lastname: Ghandi
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D002682:Chinchilla; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D051379:Mice; D056265:Microbial Interactions; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000502:physiology*; D009305:Nasopharynx / Q000382:microbiology; D010033:Otitis Media / Q000188:drug therapy / Q000382:microbiology; D053038:Quorum Sensing; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000502:physiology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D001618:beta-Lactamases
keywords: antibiotic; biofilm; otitis; persistence