Community Composition Determines Activity of Antibiotics against Multispecies Biofilms

Abstract

In young cystic fibrosis (CF) patients, <i>Staphylococcus aureus</i> is typically the most prevalent organism, while in adults, <i>Pseudomonas aeruginosa</i> is the major pathogen. More recently, it was observed that also <i>Streptococcus anginosus</i> plays an important role in exacerbations of respiratory symptoms. These species are often coisolated from CF lungs, yet little is known about whether antibiotic killing of one species is influenced by the presence of others. In the present study, we compared the activities of various antibiotics against <i>S. anginosus</i>, <i>S. aureus</i>, and <i>P. aeruginosa</i> when grown in monospecies biofilms with the activity observed in a multispecies biofilm. Our results show that differences in antibiotic activity against species grown in mono- and multispecies biofilms are species and antibiotic dependent. Fewer <i>S. anginosus</i> cells are killed by antibiotics that interfere with cell wall synthesis (amoxicillin plus sulbactam, cefepime, imipenem, meropenem, and vancomycin) in the presence of <i>S. aureus</i> and <i>P. aeruginosa</i>, while for ciprofloxacin, levofloxacin, and tobramycin, no difference was observed. In addition, we observed that the cell-free supernatant of <i>S. aureus</i>, but not that of <i>P. aeruginosa</i> biofilms, also caused this decrease in killing. Overall, <i>S. aureus</i> was more affected by antibiotic treatment in a multispecies biofilm, while for <i>P. aeruginosa</i>, no differences were observed between growth in mono- or multispecies biofilms. The results of the present study suggest that it is important to take the community composition into account when evaluating the effect of antimicrobial treatments against certain species in mixed biofilms.