Photodynamic Therapy in the Inactivation of Microorganisms

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 67507

Special Issue Editor


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Guest Editor
Departamento de Biologia, CESAM - Centro de Estudos do Ambiente e do Mar, Campus Universitário de Santiago, Universidade de Aveiro, 3810-193 Aveiro, Portugal
Interests: phage therapy; antimicrobial photodynamic therapy; alternative approaches to antibiotics
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Special Issue Information

Dear Colleagues,

This Special Issue aims to update the recent knowledge about antimicrobial photodynamic therapy. Although the efficacy of antimicrobial photodynamic therapy (aPDT) has been proved to be an alternative to the conventional antimicrobials, there is still room for new improvements namely to translate the approach to medical and environmental areas. Some important aspects are related with the development of synthetic strategies able to afford efficient photosensitizers at low cost and also of photodynamic protocols where the amount of the photosensitizer or the treatment time is decreased. It is expected that this special issue can also motivate groups to respond to the currently underutilization in clinic and environmental applications in order to obtain safe aPDT protocols to the host and to the environment.

Prof. Dr. Adelaide Almeida
Guest Editor

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Keywords

  • Antimicrobial Photodynamic Therapy
  • Photosensitizer
  • Porphyrins
  • Phenothiazines
  • Xanthenes
  • Microorganisms
  • Infection
  • Drug resistance
  • Plancktonic microorganisms
  • Biofilms

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Published Papers (11 papers)

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Editorial

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5 pages, 208 KiB  
Editorial
Photodynamic Therapy in the Inactivation of Microorganisms
by Adelaide Almeida
Antibiotics 2020, 9(4), 138; https://doi.org/10.3390/antibiotics9040138 - 25 Mar 2020
Cited by 25 | Viewed by 3825
Abstract
The growing emergence of microbial resistance to conventional antimicrobials, due their dissemination in the environment, and excessive or inadequate prescriptions, associated with the globalization of pathogenic microorganisms’ transmission, make the discovery of new effective therapies to combat infection of extreme urgency [...] Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)

Research

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10 pages, 2066 KiB  
Article
Application of Response Surface Methodology to Evaluate Photodynamic Inactivation Mediated by Eosin Y and 530 nm LED against Staphylococcus aureus
by Adriele R. Santos, Alex F. da Silva, Andréia F. P. Batista, Camila F. Freitas, Evandro Bona, Maria J. Sereia, Wilker Caetano, Noburu Hioka and Jane M. G. Mikcha
Antibiotics 2020, 9(3), 125; https://doi.org/10.3390/antibiotics9030125 - 17 Mar 2020
Cited by 10 | Viewed by 3046
Abstract
Photodynamic antimicrobial chemotherapy (PAC) is an efficient tool for inactivating microorganisms. This technique is a good approach to inactivate the foodborne microorganisms, which are responsible for one of the major public health concerns worldwide—the foodborne diseases. In this work, response surface methodology (RSM) [...] Read more.
Photodynamic antimicrobial chemotherapy (PAC) is an efficient tool for inactivating microorganisms. This technique is a good approach to inactivate the foodborne microorganisms, which are responsible for one of the major public health concerns worldwide—the foodborne diseases. In this work, response surface methodology (RSM) was used to evaluate the interaction of Eosin Y (EOS) concentration and irradiation time on Staphylococcus aureus counts and a sequence of designed experiments to model the combined effect of each factor on the response. A second-order polynomial empirical model was developed to describe the relationship between EOS concentration and irradiation time. The results showed that the derived model could predict the combined influences of these factors on S. aureus counts. The agreement between predictions and experimental observations (R2adj = 0.9159, p = 0.000034) was also observed. The significant terms in the model were the linear negative effect of photosensitizer (PS) concentration, followed by the linear negative effect of irradiation time, and the quadratic negative effect of PS concentration. The highest reductions in S. aureus counts were observed when applying a light dose of 9.98 J/cm2 (498 nM of EOS and 10 min. irradiation). The ability of the evaluated model to predict the photoinactivation of S. aureus was successfully validated. Therefore, the use of RSM combined with PAC is a promising approach to inactivate foodborne pathogens. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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12 pages, 1003 KiB  
Article
Effective Photodynamic Inactivation of 26 Escherichia coli Strains with Different Antibiotic Susceptibility Profiles: A Planktonic and Biofilm Study
by Òscar Gulías, Giselle McKenzie, Miquel Bayó, Montserrat Agut and Santi Nonell
Antibiotics 2020, 9(3), 98; https://doi.org/10.3390/antibiotics9030098 - 25 Feb 2020
Cited by 34 | Viewed by 4949
Abstract
The emergence of multidrug-resistant bacteria is a growing problem and alternative therapies are being sought to effectively address this issue. The aim of this study is to assess a range of Escherichia coli strains’ susceptibility to Methylene Blue-mediated antimicrobial photodynamic therapy and determine [...] Read more.
The emergence of multidrug-resistant bacteria is a growing problem and alternative therapies are being sought to effectively address this issue. The aim of this study is to assess a range of Escherichia coli strains’ susceptibility to Methylene Blue-mediated antimicrobial photodynamic therapy and determine if this is affected by their antibiotic-resistance profile. Two reference and twenty-four uropathogenic clinical E. coli strains were used in this study. All were tested in vitro for antimicrobial susceptibility against sixteen antibiotics. Strains underwent photodynamic treatments using the photosensitizer Methylene Blue with red light and tested in both planktonic and biofilm state. It was found that reference strain ATCC 25922 was susceptible to all tested antibiotics whereas reference strain ATCC 35218 showed resistance only to Ampicillin. With the exception of strains number 16 and 22, all of the isolated strains were multidrug-resistant according to the criteria established by the European Centre for Disease Prevention and Control and the Centre for Disease Control and Prevention, where acquired non-susceptibility to at least one agent in three or more antimicrobial categories is outlined. Photodynamic therapy induced more than 3 log10 colony-forming units’ reduction to all strains in planktonic state. Whereas when tested in biofilm state, two and a half times the original dose of methylene blue was necessary to cause a 3 log10 antimicrobial effect. There were statistically significant differences in susceptibility among the strains tested in both the planktonic and biofilm experiments. Nevertheless, antimicrobial photodynamic therapy could inactivate all multidrug-resistant strains in the planktonic and biofilm state. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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13 pages, 5589 KiB  
Article
In the Right Light: Photodynamic Inactivation of Microorganisms Using a LED-Based Illumination Device Tailored for the Antimicrobial Application
by Martina Hasenleitner and Kristjan Plaetzer
Antibiotics 2020, 9(1), 13; https://doi.org/10.3390/antibiotics9010013 - 30 Dec 2019
Cited by 19 | Viewed by 5474
Abstract
Drug-resistant bacteria threaten the health of people world-wide and cause high costs to their health systems. According to Scientific American, the number of regrettable fatalities due to the bacteria that are resistant to conventional antibiotics will sum up to 300 million until 2050 [...] Read more.
Drug-resistant bacteria threaten the health of people world-wide and cause high costs to their health systems. According to Scientific American, the number of regrettable fatalities due to the bacteria that are resistant to conventional antibiotics will sum up to 300 million until 2050 if the problem is not tackled immediately. Photodynamic Inactivation (PDI) has proven effective against microorganisms irrespective of their resistance to conventional treatment, but for the translation into clinical practice, economic, homogenous and powerful light sources holding approval as medical devices are needed. In this study we present two novel light emitting diode (LED)-based lamps (Repuls7PDI-red and Repuls7PDI-blue) tailored for application in PDI and demonstrate their photodynamic efficiency upon using either methylene blue (MB), a photoactive compound widely used in PDI, or Sodium Magnesium Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, which holds approval as food additive E140, against bacteria and fungi. Gram+ Staphylococcus aureus, Gram− Escherichia coli and the yeast Candida albicans serve as model systems. Repuls7PDI-red emits a wavelength of 635 nm and an intensity of 27.6 ± 2.4 mW·cm−2 at a distance of 13.5 cm between the light source and the target, while the Repuls7PDI-blue allows an exposure at 433 nm (within the range of violet light) (6.4 ± 0.5 mW·cm−2 at 13.5 cm). Methylene blue was photoactivated with the Repuls7PDI-red at 635 nm (25.6 J·cm−2) and allows for photokilling of E. coli by more than 6 log10 steps at a concentration of 10 µM MB. Using equal parameters, more than 99.99999% of S. aureus (20 µM MB) and 99.99% of C. albicans (50 µM MB) were killed. If blue light (Repuls7PDI-blue, 433 nm, 6.6 J·cm2) is used to trigger the production of reactive oxygen species (ROS), a photoinactivation of S. aureus (5 µM CHL, CFU reduction > 7 log10) and C. albicans (>7 log10) below the detection limit is achieved. PDI based on CHL (10 µM) using red light activation reduces the number of viable S. aureus by more than 6 log10. Our data prove that both LED-based light sources are applicable for Photodynamic Inactivation. Their easy-to-use concept, high light output and well-defined wavelength might facilitate the translation of PDI into clinical practice. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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19 pages, 4524 KiB  
Article
Photodynamic Inactivation of Candida albicans in Blood Plasma and Whole Blood
by Vera Sousa, Ana T. P. C. Gomes, Américo Freitas, Maria A. F. Faustino, Maria G. P. M. S. Neves and Adelaide Almeida
Antibiotics 2019, 8(4), 221; https://doi.org/10.3390/antibiotics8040221 - 13 Nov 2019
Cited by 22 | Viewed by 5623
Abstract
The few approved disinfection techniques for blood derivatives promote damage in the blood components, representing risks for the transfusion receptor. Antimicrobial photodynamic therapy (aPDT) seems to be a promising approach for the photoinactivation of pathogens in blood, but only three photosensitizers (PSs) have [...] Read more.
The few approved disinfection techniques for blood derivatives promote damage in the blood components, representing risks for the transfusion receptor. Antimicrobial photodynamic therapy (aPDT) seems to be a promising approach for the photoinactivation of pathogens in blood, but only three photosensitizers (PSs) have been approved, methylene blue (MB) for plasma and riboflavin and amotosalen for plasma and platelets. In this study, the efficiency of the porphyrinic photosensitizer Tri-Py(+)-Me and of the porphyrinic formulation FORM was studied in the photoinactivation of Candida albicans in plasma and in whole blood and the results were compared to the ones obtained with the already approved PS MB. The results show that FORM and Tri-Py(+)-Me are promising PSs to inactivate C. albicans in plasma. Although in whole blood the inactivation rates obtained were higher than the ones obtained with MB, further improvements are required. None of these PSs had promoted hemolysis at the isotonic conditions when hemolysis was evaluated in whole blood and after the addition of treated plasma with these PSs to concentrates of red blood cells. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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13 pages, 1607 KiB  
Article
The Remarkable Effect of Potassium Iodide in Eosin and Rose Bengal Photodynamic Action against Salmonella Typhimurium and Staphylococcus aureus
by Adriele R. Santos, Andréia F. P. Batista, Ana T. P. C. Gomes, Maria da Graça P. M. S. Neves, Maria Amparo F. Faustino, Adelaide Almeida, Noboru Hioka and Jane M. G. Mikcha
Antibiotics 2019, 8(4), 211; https://doi.org/10.3390/antibiotics8040211 - 5 Nov 2019
Cited by 23 | Viewed by 5522
Abstract
Antimicrobial photodynamic therapy (aPDT) has been shown as a promising technique to inactivate foodborne bacteria, without inducing the development of bacterial resistance. Knowing that addition of inorganic salts, such as potassium iodide (KI), can modulate the photodynamic action of the photosensitizer (PS), we [...] Read more.
Antimicrobial photodynamic therapy (aPDT) has been shown as a promising technique to inactivate foodborne bacteria, without inducing the development of bacterial resistance. Knowing that addition of inorganic salts, such as potassium iodide (KI), can modulate the photodynamic action of the photosensitizer (PS), we report in this study the antimicrobial effect of eosin (EOS) and rose bengal (RB) combined with KI against Salmonella enterica serovar Typhimurium and Staphylococcus aureus. Additionally, the possible development of bacterial resistance after this combined aPDT protocol was evaluated. The combination of EOS or RB, at all tested concentrations, with KI at 100 mM, was able to efficiently inactivate S. Typhimurium and S. aureus. This combined approach allows a reduction in the PS concentration up to 1000 times, even against one of the most common foodborne pathogenics, S. Typhimurium, a gram-negative bacterium which is not so prone to inactivation with xanthene dyes when used alone. The photoinactivation of S. Typhimurium and S. aureus by both xanthenes with KI did not induce the development of resistance. The low price of the xanthene dyes, the non-toxic nature of KI, and the possibility of reducing the PS concentration show that this technology has potential to be easily transposed to the food industry. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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11 pages, 1109 KiB  
Article
Antimicrobial Effect of Visible Light—Photoinactivation of Legionella rubrilucens by Irradiation at 450, 470, and 620 nm
by Julian Schmid, Katharina Hoenes, Petra Vatter and Martin Hessling
Antibiotics 2019, 8(4), 187; https://doi.org/10.3390/antibiotics8040187 - 15 Oct 2019
Cited by 21 | Viewed by 5062
Abstract
Despite the high number of legionella infections, there are currently no convincing preventive measures. Photoinactivation with visible light is a promising new approach and the photoinactivation sensitivity properties of planktonic Legionella rubrilucens to 450, 470, and 620 nm irradiation were thus investigated and [...] Read more.
Despite the high number of legionella infections, there are currently no convincing preventive measures. Photoinactivation with visible light is a promising new approach and the photoinactivation sensitivity properties of planktonic Legionella rubrilucens to 450, 470, and 620 nm irradiation were thus investigated and compared to existing 405 nm inactivation data for obtaining information on responsible endogenous photosensitizers. Legionella were streaked on agar plates and irradiated with different doses by light emitting diodes (LEDs) of different visible wavelengths. When irradiating bacterial samples with blue light of 450 nm, a 5-log reduction could be achieved by applying a dose of 300 J cm−2, whereas at 470 nm, a comparable reduction required about 500 J cm−2. For red irradiation at 620 nm, no inactivation could be observed, even at 500 J cm−2. The declining photoinactivation sensitivity with an increasing wavelength is consistent with the assumption of porphyrins and flavins being among the relevant photosensitizers. These results were obtained for L. rubrilucens, but there is reason to believe that its inactivation behavior is similar to that of pathogenic legionella species. Therefore, this photoinactivation might lead to new future concepts for legionella reduction and prevention in technical applications or even on or inside the human body. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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Review

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17 pages, 3725 KiB  
Review
Oxygen-Independent Antimicrobial Photoinactivation: Type III Photochemical Mechanism?
by Michael R Hamblin and Heidi Abrahamse
Antibiotics 2020, 9(2), 53; https://doi.org/10.3390/antibiotics9020053 - 31 Jan 2020
Cited by 64 | Viewed by 8087
Abstract
Since the early work of the 1900s it has been axiomatic that photodynamic action requires the presence of sufficient ambient oxygen. The Type I photochemical pathway involves electron transfer reactions leading to the production of reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl [...] Read more.
Since the early work of the 1900s it has been axiomatic that photodynamic action requires the presence of sufficient ambient oxygen. The Type I photochemical pathway involves electron transfer reactions leading to the production of reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyl radicals), while the Type II pathway involves energy transfer from the PS (photosensitizer) triplet state, leading to production of reactive singlet oxygen. The purpose of the present review is to highlight the possibility of oxygen-independent photoinactivation leading to the killing of pathogenic bacteria, which may be termed the “Type III photochemical pathway”. Psoralens can be photoactivated by ultraviolet A (UVA) light to produce DNA monoadducts and inter-strand cross-links that kill bacteria and may actually be more effective in the absence of oxygen. Tetracyclines can function as light-activated antibiotics, working by a mixture of oxygen-dependent and oxygen independent pathways. Again, covalent adducts may be formed in bacterial ribosomes. Antimicrobial photodynamic inactivation can be potentiated by addition of several different inorganic salts, and in the case of potassium iodide and sodium azide, bacterial killing can be achieved in the absence of oxygen. The proposed mechanism involves photoinduced electron transfer that produces reactive inorganic radicals. These new approaches might be useful to treat anaerobic infections or infections in hypoxic tissue. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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21 pages, 1305 KiB  
Review
Blue Light Disinfection in Hospital Infection Control: Advantages, Drawbacks, and Pitfalls
by João Cabral and Rodrigues AG
Antibiotics 2019, 8(2), 58; https://doi.org/10.3390/antibiotics8020058 - 7 May 2019
Cited by 33 | Viewed by 8724
Abstract
Hospital acquired infections (HAIs) are a serious problem that potentially affects millions of patients whenever in contact with hospital settings. Worsening the panorama is the emergence of antimicrobial resistance by most microorganisms implicated in HAIs. Therefore, the improvement of the actual surveillance methods [...] Read more.
Hospital acquired infections (HAIs) are a serious problem that potentially affects millions of patients whenever in contact with hospital settings. Worsening the panorama is the emergence of antimicrobial resistance by most microorganisms implicated in HAIs. Therefore, the improvement of the actual surveillance methods and the discovery of alternative approaches with novel modes of action is vital to overcome the threats created by the emergence of such resistances. Light therapy modalities represent a viable and effective alternative to the conventional antimicrobial treatment and can be preponderant in the control of HAIs, even against multidrug resistant organisms (MDROs). This review will initially focus on the actual state of HAIs and MDROs and which methods are currently available to fight them, which is followed by the exploration of antimicrobial photodynamic therapy (aPDT) and antimicrobial blue light therapy (aBLT) as alternative approaches to control microorganisms involved in HAIs. The advantages and drawbacks of BLT relatively to aPDT and conventional antimicrobial drugs as well as its potential applications to destroy microorganisms in the healthcare setting will also be discussed. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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Other

10 pages, 890 KiB  
Opinion
Antimicrobial Photodynamic Therapy in the Control of COVID-19
by Adelaide Almeida, M. Amparo F. Faustino and Maria G. P. M. S. Neves
Antibiotics 2020, 9(6), 320; https://doi.org/10.3390/antibiotics9060320 - 11 Jun 2020
Cited by 85 | Viewed by 11293
Abstract
Antimicrobial photodynamic therapy (aPDT), using well known, safe and cost-effective photosensitizers, such as phenothiazines, e.g., methylene blue (MB), or porphyrins, e.g., protoporphyrin-IX (PP-IX), might help to mitigate the COVID-19 either to prevent infections or to develop photoactive fabrics (e.g., masks, suits, gloves) to [...] Read more.
Antimicrobial photodynamic therapy (aPDT), using well known, safe and cost-effective photosensitizers, such as phenothiazines, e.g., methylene blue (MB), or porphyrins, e.g., protoporphyrin-IX (PP-IX), might help to mitigate the COVID-19 either to prevent infections or to develop photoactive fabrics (e.g., masks, suits, gloves) to disinfect surfaces, air and wastewater, under artificial light and/or natural sunlight. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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5 pages, 166 KiB  
Commentary
A New Penicillin?
by Mark Wainwright
Antibiotics 2020, 9(3), 117; https://doi.org/10.3390/antibiotics9030117 - 11 Mar 2020
Cited by 5 | Viewed by 4218
Abstract
The spectre of antimicrobial resistance looms very large indeed in the 21st century; the supply of efficacious conventional drugs is short and not guaranteed, for various reasons. It is time to look elsewhere for answers and for protocols which might be used in [...] Read more.
The spectre of antimicrobial resistance looms very large indeed in the 21st century; the supply of efficacious conventional drugs is short and not guaranteed, for various reasons. It is time to look elsewhere for answers and for protocols which might be used in tandem with our diminishing arsenal in order to protect vital drugs. This could bridge the gap before new development in conventional antimicrobial therapy occurs, or might be a longer-term solution, particularly in the area of infectious disease prophylaxis (conventional-sensitive or -resistant). Reliable and safe protocols have been developed for the use of photoantimicrobials in this respect, offering much greater coverage, in terms of the microbial target, than Fleming ever imagined. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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