Blue laser light inhibits biofilm formation in vitro and in vivo by inducing oxidative stress

Rupel, Katia; Zupin, Luisa; Ottaviani, Giulia; Bertani, Iris; Martinelli, Valentina; Porrelli, Davide; Vodret, Simone; Vuerich, Roman; Silva, Daniel Passos da; Bussani, Rossana; Crovella, Sérgio; Parsek, Matthew R.; Venturi, Vittorio; Lenarda, Roberto Di; Biasotto, Matteo; Zacchigna, Serena

doi:10.1038/s41522-019-0102-9

Cited by 55 publications

(44 citation statements)

References 35 publications

(50 reference statements)

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“…Concentrations of 50 and 100 nM CUR‐SPM were employed, alongside with increasing concentrations of free CUR (5 μM, 10 μM, 20 μM, 50 μM, 100 μM, 200 μM). For every condition, the wells were irradiated with three sublethal blue laser protocols (L1, L2 and L3 as described in Table 1), based on our previous experience with antimicrobial blue laser irradiation [16]. Bacterial growth after 24 hours was evaluated by measuring the OD 600 and compared with nontreated bacteria (CTRL).…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light

Rupel

Zupin

Brich

et al. 2020

Journal of Biophotonics

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The aim of this work was to assess the antimicrobial efficacy on Pseudomonas aeruginosa of nanomicelles loaded with curcumin (CUR) alone and activated by blue laser light in an antimicrobial photodynamic therapy (APDT) approach. First, free CUR in liquid suspension and loaded in three amphiphilic nanomicelles (CUR‐DAPMA, CUR‐SPD and CUR‐SPM) were tested both on bacteria and keratinocytes. While free CUR exerted limited efficacy showing moderate cytotoxicity, a strong inhibition of bacterial growth was obtained using all three nanosystems without toxicity on eukaryotic cells. CUR‐SPM emerged as the most effective, and was therefore employed in APDT experiments. Among the three sublethal blue laser (λ 445 nm) protocols tested, the ones characterized by a fluence of 18 and 30 J/cm2 further decreased the antimicrobial concentration to 50 nM. The combination of blue laser APDT with CUR‐SPM nanomicelles results in an effective synergistic activity that represents a promising novel therapeutic approach on resistant species.

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Section: Methodsmentioning

confidence: 99%

Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light

Rupel

Zupin

Brich

et al. 2020

Journal of Biophotonics

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“…In vivo studies in mouse burns showed that blue-light exposure could drastically reduce bacterial load and effectively protect mice from lethal infection with P. aeruginosa [ 312 ]. Blue light presumably exerts its effect on bacterial cells by exciting porphyrins which then generate ROS, as suggested by the resistance to blue light exhibited by a P. aeruginosa mutant defective in porphyrin biosynthetis [ 313 ]. Additionally, ultraviolet C light has been shown to efficiently eradicate Pseudomonas biofilms on precontaminated catheter-like tubes [ 314 ].…”

Section: Control Of Biofilm Infectionsmentioning

confidence: 99%

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

et al. 2020

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Multidrug resistant bacteria are a global threat for human and animal health. However, they are only part of the problem of antibiotic failure. Another bacterial strategy that contributes to their capacity to withstand antimicrobials is the formation of biofilms. Biofilms are associations of microorganisms embedded a self-produced extracellular matrix. They create particular environments that confer bacterial tolerance and resistance to antibiotics by different mechanisms that depend upon factors such as biofilm composition, architecture, the stage of biofilm development, and growth conditions. The biofilm structure hinders the penetration of antibiotics and may prevent the accumulation of bactericidal concentrations throughout the entire biofilm. In addition, gradients of dispersion of nutrients and oxygen within the biofilm generate different metabolic states of individual cells and favor the development of antibiotic tolerance and bacterial persistence. Furthermore, antimicrobial resistance may develop within biofilms through a variety of mechanisms. The expression of efflux pumps may be induced in various parts of the biofilm and the mutation frequency is induced, while the presence of extracellular DNA and the close contact between cells favor horizontal gene transfer. A deep understanding of the mechanisms by which biofilms cause tolerance/resistance to antibiotics helps to develop novel strategies to fight these infections.

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“…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 ). Thus, our data suggest the application of aPDT is an effective antimicrobial strategy that both interferes with maintenance of bacterial viability and disorganizes and compromises the integrity of the biofilm structure.…”

Section: Discussionmentioning

confidence: 99%

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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Blue laser light inhibits biofilm formation in vitro and in vivo by inducing oxidative stress

Cited by 55 publications

References 35 publications

Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light

Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light

Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

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

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