title: Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis.
abstract: Streptococcus pyogenes is the bacterium most frequently isolated from patients with pharyngitis. Although various antibiotics including penicillin are effective, antibiotic treatment failure in cases of streptococcal pharyngitis have been reported. Herein, we investigated mechanisms associated with recurrent streptococcal pharyngitis. Clinically isolated S. pyogenes strains showed serotype-specific features, with emm12 strains most frequently detected and emm6 strains more likely to produce biofilm. The architectures of formed biofilms were observed using a fluorescence microscope with Live/Dead staining. Furthermore, various cationic antimicrobial peptides were tested to evaluate their inhibitory activities toward biofilms formed by S. pyogenes. After treatments with high concentrations of antibiotics, S. pyogenes survived in biofilm even when dead bacterial cells covered the surface. Other findings demonstrated that some antimicrobial peptides have inhibitory effects on forming and formed biofilm. Moreover, emm4, emm6, and emm75 strains showed significantly higher levels of invasion capacity into Detroit 562 cells than strains with other genotypes. Additionally, more than half of the strains temporarily escaped killing by penicillin alone by internalization into epithelial cells, even when the antibiotic concentration used was greater than the 10-fold minimum inhibitory concentration (MIC) for planktonic S. pyogenes. Also, combined administrations of multiple antibiotics were more effective to eradicate strains more likely to be internalized. Finally, flow cytometric analyses demonstrated that emm12 strains with higher invasive capabilities expressed PrtF1 protein on the bacterial surface. These findings suggest that S. pyogenes isolated from patients with recurrent streptococcal pharyngitis have emm type-specific features that allow escape from eradication by antibiotics.
authors: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Taiji
authors: T
authors: Ogawa
authors: Yutaka
authors: Y
authors: Terao
authors: Hisashi
authors: H
authors: Okuni
authors: Keiko
authors: K
authors: Ninomiya
authors: Hiroshi
authors: H
authors: Sakata
authors: Kazunori
authors: K
authors: Ikebe
authors: Yoshinobu
authors: Y
authors: Maeda
authors: Shigetada
authors: S
authors: Kawabata
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000382:microbiology*; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D009305:Nasopharynx / Q000166:cytology / Q000382:microbiology; D010612:Pharyngitis / Q000188:drug therapy* / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D017211:Treatment Failure
chemical_list: D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C078635:fibronectin-binding proteins, bacterial; C014689:streptococcal M protein