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

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.

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Antimicrobial photodynamic therapy using chlorin e6 with halogen light for acne bacteria-induced inflammation

Life Sciences ◽

10.1016/j.lfs.2014.12.029 ◽

2015 ◽

Vol 124 ◽

pp. 56-63 ◽

Cited By ~ 33

Author(s):

Yu-Mi Jeon ◽

Hwan-Suk Lee ◽

Dongjun Jeong ◽

Hae-Keun Oh ◽

Kyu-Hwan Ra ◽

...

Keyword(s):

Photodynamic Therapy ◽

Chlorin E6 ◽

Antimicrobial Photodynamic Therapy ◽

Halogen Light

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Potentiation effects of antimicrobial photodynamic therapy on quorum sensing genes expression: A promising treatment for multi-species bacterial biofilms in burn wound infections

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2020.101717 ◽

2020 ◽

Vol 30 ◽

pp. 101717 ◽

Cited By ~ 2

Author(s):

Maryam Pourhajibagher ◽

Hassan Mahmoudi ◽

Loghman Rezaei-soufi ◽

Mohammad Yousef Alikhani ◽

Abbas Bahador

Keyword(s):

Photodynamic Therapy ◽

Quorum Sensing ◽

Bacterial Biofilms ◽

Antimicrobial Photodynamic Therapy ◽

Wound Infections ◽

Burn Wound ◽

Genes Expression ◽

Promising Treatment

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Antimicrobial photodynamic therapy reduces adhesion capacity and biofilm formation of Candida albicans from induced oral candidiasis in mice

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2019.06.010 ◽

2019 ◽

Vol 27 ◽

pp. 402-407 ◽

Cited By ~ 10

Author(s):

Juliana Cabrini Carmello ◽

Fernanda Alves ◽

Fernanda G. Basso ◽

Carlos Alberto de Souza Costa ◽

Antônio Cláudio Tedesco ◽

...

Keyword(s):

Candida Albicans ◽

Photodynamic Therapy ◽

Biofilm Formation ◽

Oral Candidiasis ◽

Antimicrobial Photodynamic Therapy

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Propolis nanoparticle enhances the potency of antimicrobial photodynamic therapy against Streptococcus mutans in a synergistic manner

Scientific Reports ◽

10.1038/s41598-020-72119-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Shima Afrasiabi ◽

Maryam Pourhajibagher ◽

Nasim Chiniforush ◽

Abbas Bahador

Keyword(s):

Photodynamic Therapy ◽

Streptococcus Mutans ◽

Biofilm Formation ◽

Synergistic Effects ◽

Fibroblast Cell ◽

Human Gingival Fibroblast ◽

Gingival Fibroblast ◽

Antimicrobial Photodynamic Therapy ◽

The Individual

Abstract Less invasive removal approaches have been recommended for deep caries lesions. Antimicrobial photodynamic therapy (aPDT) and propolis nanoparticle (PNP) are highlighted for the caries management plan. Evidence is lacking for an additive effect of combination PNP with photosensitizer (PS) in aPDT. This study aimed to investigate the individual and synergistic effects of chlorophyllin-phycocyanin mixture (PhotoActive+) and toluidine blue O (TBO) as PSs in combination with PNP in the aPDT process (aPDTplus) against major important virulence factors of Streptococcus mutans. Following characterization, biocompatibility of the PSs alone, or in combination with PNP were investigated on human gingival fibroblast cell. The in vitro synergy of PhotoActive+ or TBO and PNP was evaluated by the checkerboard method. The bacteria's virulence properties were surveyed in the presence of the PSs, individually as well as in combination. When the PSs were examined in combination (synergistic effect, FIC Index < 0.5), a stronger growth inhibitory activity was exhibited than the individual PSs. The biofilm formation, as well as genes involved in biofilm formation, showed greater suppression when the PSs were employed in combination. Overall, the results of this study suggest that the combination of PhotoActive+ or TBO with PNP with the least cytotoxicity effects and the highest antimicrobial activites would improve aPDT outcomes, leading to synergistic effects and impairing the virulence of S. mutans.

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Lucilia sericata Chymotrypsin Disrupts Protein Adhesin-Mediated Staphylococcal Biofilm Formation

Applied and Environmental Microbiology ◽

10.1128/aem.03689-12 ◽

2012 ◽

Vol 79 (4) ◽

pp. 1393-1395 ◽

Cited By ~ 35

Author(s):

Llinos G. Harris ◽

Yamni Nigam ◽

James Sawyer ◽

Dietrich Mack ◽

David I. Pritchard

Keyword(s):

Staphylococcus Aureus ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Lucilia Sericata ◽

Bacterial Biofilm ◽

Bacterial Biofilms ◽

Formation Mechanisms ◽

Chronic Infections ◽

Content Type ◽

Effective Activity

ABSTRACTStaphylococcus aureusandStaphylococcus epidermidisbiofilms cause chronic infections due to their ability to form biofilms. The excretions/secretions ofLucilia sericatalarvae (maggots) have effective activity for debridement and disruption of bacterial biofilms. In this paper, we demonstrate how chymotrypsin derived from maggot excretions/secretions disrupts protein-dependent bacterial biofilm formation mechanisms.

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Synergistic in vitro effects of indocyanine green and ethylenediamine tetraacetate-mediated antimicrobial photodynamic therapy combined with antibiotics for resistant bacterial biofilms in diabetic foot infection

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2019.01.010 ◽

2019 ◽

Vol 25 ◽

pp. 300-308 ◽

Cited By ~ 10

Author(s):

Xuemei Li ◽

Wanting Huang ◽

Xiaoying Zheng ◽

Shufang Chang ◽

Chengwei Liu ◽

...

Keyword(s):

Photodynamic Therapy ◽

Indocyanine Green ◽

Diabetic Foot ◽

Bacterial Biofilms ◽

Antimicrobial Photodynamic Therapy ◽

Diabetic Foot Infection ◽

In Vitro Effects ◽

Ethylenediamine Tetraacetate

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Laboratory Evolution of Microbial Interactions in Bacterial Biofilms

Journal of Bacteriology ◽

10.1128/jb.01018-15 ◽

2016 ◽

Vol 198 (19) ◽

pp. 2564-2571 ◽

Cited By ~ 39

Author(s):

Marivic Martin ◽

Theresa Hölscher ◽

Anna Dragoš ◽

Vaughn S. Cooper ◽

Ákos T. Kovács

Keyword(s):

Social Interactions ◽

Biofilm Formation ◽

Microbial Interactions ◽

Burkholderia Cenocepacia ◽

Bacterial Biofilms ◽

Laboratory Evolution ◽

Content Type ◽

Microbial Adaptation ◽

Adaptive Processes ◽

Facilitative Interactions

Microbial adaptation is conspicuous in essentially every environment, but the mechanisms of adaptive evolution are poorly understood. Studying evolution in the laboratory under controlled conditions can be a tractable approach, particularly when new, discernible phenotypes evolve rapidly. This is especially the case in the spatially structured environments of biofilms, which promote the occurrence and stability of new, heritable phenotypes. Further, diversity in biofilms can give rise to nascent social interactions among coexisting mutants and enable the study of the emerging field of sociomicrobiology. Here, we review findings from laboratory evolution experiments with eitherPseudomonas fluorescensorBurkholderia cenocepaciain spatially structured environments that promote biofilm formation. In both systems, ecotypes with overlapping niches evolve and produce competitive or facilitative interactions that lead to novel community attributes, demonstrating the parallelism of adaptive processes captured in the lab.

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Escherichia coli Biofilms Have an Organized and Complex Extracellular Matrix Structure

mBio ◽

10.1128/mbio.00645-13 ◽

2013 ◽

Vol 4 (5) ◽

Cited By ~ 105

Author(s):

Chia Hung ◽

Yizhou Zhou ◽

Jerome S. Pinkner ◽

Karen W. Dodson ◽

Jan R. Crowley ◽

...

Keyword(s):

Escherichia Coli ◽

Extracellular Matrix ◽

Biofilm Formation ◽

Developmental Stages ◽

Three Dimensional ◽

Bacterial Biofilms ◽

Content Type ◽

Abiotic Surfaces ◽

Biochemical Analyses ◽

Biofilm Development

ABSTRACTBacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenicEscherichia coli(UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community.IMPORTANCEBacteria can form biofilms in diverse niches, including abiotic surfaces, living cells, and at the air-liquid interface of liquid media. Encasing these cellular communities is a self-produced extracellular matrix (ECM) that can be composed of proteins, polysaccharides, and nucleic acids. The ECM protects biofilm bacteria from environmental insults and also makes the dissolution of biofilms very challenging. As a result, formation of biofilms within humans (during infection) or on industrial material (such as water pipes) has detrimental and costly effects. In order to combat bacterial biofilms, a better understanding of components required for biofilm formation and the ECM is required. This study defined the ECM composition and architecture of floating pellicle biofilms formed byEscherichia coli.

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Effect of Antimicrobial Photodynamic Therapy Using Indocyanine Green Doped with Chitosan Nanoparticles on Biofilm Formation-Related Gene Expression of Aggregatibacter actinomycetemcomitans

Frontiers in Dentistry ◽

10.18502/fid.v16i3.1590 ◽

2019 ◽

Author(s):

Mehdi Rostami Rad ◽

Maryam Pourhajibagher ◽

Amir Reza Reza Rokn ◽

Hamid Reza Barikani ◽

Abbas Bahador

Keyword(s):

Gene Expression ◽

Photodynamic Therapy ◽

Indocyanine Green ◽

Diode Laser ◽

Virulence Factor ◽

Biofilm Formation ◽

Chitosan Nanoparticles ◽

Aggregatibacter Actinomycetemcomitans ◽

Expression Level ◽

Antimicrobial Photodynamic Therapy

Objectives: Eradication of Aggregatibacter actinomycetemcomitans (A. action-mycetemcomitans), as an opportunistic periodontopathogen, and inhibition of its virulence factor expression require a new adjunctive therapeutic method. In this study, we accessed the expression level of rcpA gene, as a virulence factor associated with A. actinomycetemcomitans biofilm formation, following treatment by antimicrobial photodynamic therapy (aPDT) using indocyanine green (ICG) doped with chitosan nanoparticles (CS-NPs@ICG). Materials and Methods: CS-NPs@ICG was synthesized and examined using scanning electron microscopy (SEM). A. actinomycetemcomitans ATCC 33384 strain was treated with CS-NPs@ICG, as a photosensitizer, which was excited with a diode laser at the wavelength of 810 nm with the energy density of 31.2 J/cm2. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the changes in rcpA gene expression level. Results: Synthetized CS-NPs@ICG was confirmed via SEM. The results revealed that CS-NPs@ICG-mediated aPDT could significantly decrease rcpA gene expression to 13.2-fold (P<0.05). There was a remarkable difference between aPDT using CS-NPs@ICG and ICG (P<0.05). The diode laser, ICG, and CS-NPs@ICG were unable to significantly downregulate rcpA gene expression (P>0.05). Conclusion: aPDT with CS-NPs@ICG leads to a decrease of the virulence factor of A. actinomycetemcomitans and can be used as an adjunct to routine treatments for successful periodontal therapy in vivo.

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