Abstract

Moraxella catarrhalis, Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi) are ubiquitous upper respiratory opportunistic pathogens. Together, these three microbes are the most common causative bacterial agents of pediatric otitis media (OM) and have therefore been characterized as the primary human otopathogens. OM is the most prevalent bacterial infection in children and the primary reason for antibiotic administration in this population. Moreover, biofilm formation has been confirmed as a primary mechanism of chronic and recurrent OM disease. As bacterial biofilms are inherently metabolically recalcitrant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with the photosensitizer chlorin e6 (Ce6) against planktonic as well as biofilm-associated M. catarrhalis, S. pneumoniae, and NTHi. Our data indicate aPDT with Ce6 elicits significant bactericidal activity against both planktonic cultures and established biofilms formed by the three major otopathogens (with an efficacy of ≥99.9% loss of viability). Notably, the implementation of a novel, dual-treatment aPDT protocol resulted in this disinfectant effect on biofilm-associated bacteria and, importantly, inhibited bacterial regrowth 24 h posttreatment. Taken together, these data suggest this novel Ce6-aPDT treatment may be a powerful and innovative therapeutic strategy to effectively treat and eradicate bacterial OM infections and, significantly, prevent the development of recurrent disease.IMPORTANCE Otitis media (OM), or middle ear disease, is the most prevalent bacterial infection in children and the primary reason for antibiotic use and surgical intervention in the pediatric population. Biofilm formation by the major bacterial otopathogens, Moraxella catarrhalis, Streptococcus pneumoniae, and nontypeable Haemophilus influenzae, has been shown to occur within the middle ears of OM patients and is a key factor in the development of recurrent disease, which may result in hearing impairment and developmental delays. Bacterial biofilms are inherently impervious to most antibiotics and present a significant challenge to the immune system. In this study, we demonstrate that antimicrobial photodynamic therapy (aPDT) using the photosensitizer chlorin e6 elicits significant bactericidal activity versus planktonic and biofilm-associated otopathogens and supports further analyses of this novel, efficacious, and promising technology as an adjunctive treatment for acute and recurrent OM.

Highlights

  • Moraxella catarrhalis, Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi) are ubiquitous upper respiratory opportunistic pathogens

  • Antibiofilm efficacy against otopathogenic bacteria is critical, as previous studies have demonstrated that biofilm formation occurs clinically in vivo within the middle ears and on the adenoids of pediatric Otitis media (OM) patients and that biofilm-associated organisms are often refractory to antibiotic treatments and responsible for disease recurrence [13,14,15,16]

  • As biofilm-associated bacteria may be released into the environment and colonize new surfaces or cause disseminated disease, we investigated whether the observed decrease in biofilmassociated bacterial CFU following antimicrobial photodynamic therapy (aPDT) were due to the loss of cell viability or bacterial detachment from the biofilm and release into the surrounding environment

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Summary

Introduction

Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi) are ubiquitous upper respiratory opportunistic pathogens. We demonstrate that antimicrobial photodynamic therapy (aPDT) using the photosensitizer chlorin e6 elicits significant bactericidal activity versus planktonic and biofilm-associated otopathogens and supports further analyses of this novel, efficacious, and promising technology as an adjunctive treatment for acute and recurrent OM. Otitis media (OM), or middle ear disease, is the most prevalent pediatric bacterial infection as well as the single most common reason for antibiotic use in young children Has this treatment approach resulted in a rapid increase in microbial resistance, but recent studies have suggested that frequent antimicrobial use early in life, often due to recurrent OM, is correlated with the subsequent development of allergic diseases during childhood [1, 2]. The data presented in this report demonstrate Ce6-aPDT elicits significant bactericidal activity versus the three primary bacterial otopathogens, suggesting that this technology warrants further analysis as a novel antimicrobial treatment for the prevention of recurrent OM

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