title: Therapeutic failures of antibiotics used to treat macrolide-susceptible Streptococcus pyogenes infections may be due to biofilm formation.
abstract: Streptococcus pyogenes infections often fail to respond to antibiotic therapy, leading to persistent throat carriage and recurrent infections. Such failures cannot always be explained by the occurrence of antibiotic resistance determinants, and it has been suggested that S. pyogenes may enter epithelial cells to escape antibiotic treatment. We investigated 289 S. pyogenes strains isolated from different clinical sources to evaluate their ability to form biofilm as an alternative method to escape antibiotic treatment and host defenses. Up to 90% of S. pyogenes isolates, from both invasive and noninvasive infections, were able to form biofilm. Specific emm types, such as emm6, appeared to be more likely to produce biofilm, although variations within strains belonging to the same type might suggest biofilm formation to be a trait of individual strains rather than a general attribute of a serotype. Interestingly, erythromycin-susceptible isolates formed a significantly thicker biofilm than resistant isolates (P < 0.05). Among resistant strains, those carrying the erm class determinants formed a less organized biofilm than the mef(A)-positive strains. Also, prtF1 appeared to be negatively associated with the ability to form biofilm (P < 0.01). Preliminary data on a selection of strains indicated that biofilm-forming isolates entered epithelial cells with significantly lower efficiency than biofilm-negative strains. We suggest that prtF1-negative macrolide-susceptible or mef(A)-carrying isolates, which are poorly equipped to enter cells, may use biofilm to escape antimicrobial treatments and survive within the host. In this view, biofilm formation by S. pyogenes could be responsible for unexplained treatment failures and recurrences due to susceptible microorganisms.
authors.affiliation: Reparto di Malattie Batteriche Respiratorie e Sistemiche, Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Roma, Italy. baldassa@iss.it
authors.forename: Lucilla
authors.initials: L
authors.lastname: Baldassarri
authors.forename: Roberta
authors.initials: R
authors.lastname: Creti
authors.forename: Simona
authors.initials: S
authors.lastname: Recchia
authors.forename: Monica
authors.initials: M
authors.lastname: Imperi
authors.forename: Bruna
authors.initials: B
authors.lastname: Facinelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Giovanetti
authors.forename: Marco
authors.initials: M
authors.lastname: Pataracchia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Alfarone
authors.forename: Graziella
authors.initials: G
authors.lastname: Orefici
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology; D004917:Erythromycin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018942:Macrolides / Q000494:pharmacology* / Q000627:therapeutic use; D008565:Membrane Proteins / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; C078635:fibronectin-binding proteins, bacterial; D004917:Erythromycin