Photodynamic therapy mediated by chlorin-type photosensitizers against Streptococcus mutans biofilms

Garcia, Maíra Terra; Pereira, André Henrique Correia; Figueiredo-Godoi, Lívia Mara Alves; Jorge, Antônio Olavo Cardoso; Ferreira‐Strixino, Juliana; Junqueira, Juliana Campos

doi:10.1016/j.pdpdt.2018.08.012

Cited by 43 publications

(24 citation statements)

References 43 publications

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“…The comparative experiments evaluating the sensitivity of Gram-negative M. catarrhalis and NTHi and Gram-positive S. pneumoniae , using low concentrations of PS and constant light intensity and irradiation periods, indicate highly successful inactivation of both planktonic and biofilm-associated organisms irrespective of Gram classification. However, although we obtained superior and sustained eradication following the dual-treatment protocol, dark toxicity of the PS toward S. pneumoniae became evident, consistent with previous reports describing a bactericidal effect of PSs alone, in the absence of illumination, toward Gram-positive organisms due to a more rapid intracellular drug accumulation ( 29 , 31 – 33 ). Likewise, the observed antimicrobial effect of light exposure alone has been demonstrated in multiple bacterial species, with Gram-negative bacteria often showing increased sensitivity to photoinactivation, which has been attributed to the presence of endogenously synthesized cellular porphyrins that act as native PSs and, upon light activation, cause lethal ROS production ( 21 , 32 , 34 , 35 ).…”

Section: Discussionsupporting

confidence: 90%

Antimicrobial Photodynamic Therapy with Chlorin e6 Is Bactericidal against Biofilms of the Primary Human Otopathogens

Luke-Marshall

Hansen

Shafirstein

et al. 2020

mSphere

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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.

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Section: Discussionsupporting

confidence: 90%

Antimicrobial Photodynamic Therapy with Chlorin e6 Is Bactericidal against Biofilms of the Primary Human Otopathogens

Luke-Marshall

Hansen

Shafirstein

et al. 2020

mSphere

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“…Chlorin-based PSs are now currently introduced into experimental medicine [8][9][10] and clinical practice [11][12][13][14] due to high efficiency and two pronounced absorption peaks in different bands of visible range (Fig. 1) that together with fluorescent properties provide additional opportunities for improving irradiation and monitoring protocols.…”

Section: Introductionmentioning

confidence: 99%

“…Most of PDT protocols with chlorin-based PSs, especially, tumor treatment protocols, employ irradiation wavelengths around 662 nm to ensure deeper light penetration. [8][9][10][11][12] There are several reports on the application of blue spectral range with such PSs as aminolevulinic acid or methyl aminolevulinate, 6,20,25,26 which also have several absorption peaks including red and blue bands; however, the reported applications with chlorin-based PS are very limited. 14,24 In our previous paper, 24 we reported on a clinical study of antimicrobial PDT of pharynx chronic inflammatory diseases with topical application of chlorin-based PS and irradiation wavelength of 405 nm.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of single- and dual-wavelength photodynamic therapy regimes with chlorin-based photosensitizers: animal study

Kurakina¹,

Khilov²,

Shakhova

et al. 2019

J. Biomed. Opt.

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Comparative analysis of single-and dual-wavelength photodynamic therapy regimes with chlorin-based photosensitizers: animal study," J.Abstract. Two pronounced absorption peaks in blue and red ranges of the chlorin-based photosensitizer (PS) absorption spectrum provide additional benefits in photodynamic therapy (PDT) performance. Differing optical properties of biological tissues in these ranges allow for both dual-wavelength diagnostics and PDT performance. We provide a comparative analysis of different PDT regimes performed with blue and red lights and their combination, with doses varying from 50 to 150 J∕cm 2 . The study was performed on the intact skin of a rabbit ear inner surface, with the use of chlorin e6 as a PS. PDT procedure protocol included monitoring of the treated site with fluorescence imaging technique to evaluate PS accumulation and photobleaching, as well as with optical coherence tomography (OCT) to register morphological and functional responses of the tissue. Optical diagnostic observations were compared with the results of histopathology examination. We demonstrated that PDT procedures with the considered regimes induce weaker organism reaction manifested by edema in normal tissue as compared to irradiation-only exposures with the same light doses. The light doses delivered with red light induce weaker tissue reaction as compared to the same doses delivered with blue light only or with a combination of red and blue lights in equal parts. Results of in-vivo OCT monitoring of tissue reaction are in agreement with the results of histopathology study.

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“…Uma das limitações deste estudo, referente à aPDT e à metodologia proposta de indução de lesão com apenas o S. mutans, pode estar relacionada ao fato de que existem milhares de bactérias na microbiota oral e que juntas são capazes de se agregar e formar um biofilme complexo. Sendo assim, é possível encontrar na literatura que as bactérias são mais resistentes à aPDT quando estão organizadas em biofilmes (Terra Garcia et al, 2018). Ainda nesse sentido, estudos futuros que façam o uso de abordagens alternativas, como um fotossensibilizador que possua maior capacidade de penetração, podem ser necessários (de Freitas et al, 2017).…”

Section: Discussionunclassified

“…Porém, como a patogenicidade de S. mutans está intimamente relacionado à sua capacidade de formar biofilmes em superfícies dentárias, estudos de aPDT com essa cepa isolada em condições in vitro ainda são de grande valia (Terra Garcia et al, 2018).…”

Section: Discussionunclassified

Eficácia do uso de lasers ou clorexidina na redução microbiana em lesões de cárie produzidas artificialmente

Rodrigues¹

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Photodynamic therapy mediated by chlorin-type photosensitizers against Streptococcus mutans biofilms

Cited by 43 publications

References 43 publications

Antimicrobial Photodynamic Therapy with Chlorin e6 Is Bactericidal against Biofilms of the Primary Human Otopathogens

Antimicrobial Photodynamic Therapy with Chlorin e6 Is Bactericidal against Biofilms of the Primary Human Otopathogens

Comparative analysis of single- and dual-wavelength photodynamic therapy regimes with chlorin-based photosensitizers: animal study

Eficácia do uso de lasers ou clorexidina na redução microbiana em lesões de cárie produzidas artificialmente

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