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Microorganisms
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Photodynamic Therapy: Applications against Microorganisms
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Photodynamic Therapy: Applications against Microorganisms

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 11906

Special Issue Editor

Prof. Dr. Adelaide Almeida

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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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The increasing number of drug-resistant microbial infections is an emerging global health crisis that is driving a growing demand for alternative therapies to conventional antimicrobials. Antimicrobial photodynamic therapy (aPDT) is a likely approach to deal with this devastating scenario of drug resistance, but with a few exceptions (e.g., using 5-aminolevulinic acid and hematoporphyrin derivatives as aPDT mediators), no protocol currently holds a marketing authorisation that would allow its free use in human medicine. Although compassionate treatments permit the use of unapproved medicines to treat patients with no more approved therapeutic options, aPDT has not yet been used with this option. Moreover, as drug resistance is not only a problem of human medicine, occurring also in animal and environmental sectors, it is important to extend the aPDT efforts to other areas such as veterinary medicine, aquaculture, agriculture and food industry.

As antimicrobial resistance continues to increase, there is much to be done in order to streamline aPDT efforts, particularly in terms of developing efficient protocols and simple synthetic strategies able to afford effective, inexpensive and safe photosensitizers. It is expected that this Special Issue can motivate physicians and researchers to respond to the current underutilization of aPDT in human, animal and environmental sectors in order to develop effective and safe therapeutics and applications.

Prof. Dr. Adelaide Almeida
Guest Editor

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Published Papers (4 papers)

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Research

17 pages, 3232 KiB  
Article
Evaluation of a Luminometric Cell Counting System in Context of Antimicrobial Photodynamic Inactivation
by Moritz Lehnig, Sarah Glass, Norman Lippmann, Svitlana Ziganshyna, Volker Eulenburg and Robert Werdehausen
Microorganisms 2022, 10(5), 950; https://doi.org/10.3390/microorganisms10050950 - 30 Apr 2022
Cited by 3 | Viewed by 2554
Abstract
Antimicrobial resistance belongs to the most demanding medical challenges, and antimicrobial photodynamic inactivation (aPDI) is considered a promising alternative to classical antibiotics. However, the pharmacologic characterization of novel compounds suitable for aPDI is a tedious and time-consuming task that usually requires preparation of [...] Read more.
Antimicrobial resistance belongs to the most demanding medical challenges, and antimicrobial photodynamic inactivation (aPDI) is considered a promising alternative to classical antibiotics. However, the pharmacologic characterization of novel compounds suitable for aPDI is a tedious and time-consuming task that usually requires preparation of bacterial cultures and counting of bacterial colonies. In this study, we established and utilized a luminescence-based microbial cell viability assay to analyze the aPDI effects of two porphyrin-based photosensitizers (TMPyP and THPTS) on several bacterial strains with antimicrobial resistance. We demonstrate that after adaptation of the protocol and initial calibration to every specific bacterial strain and photosensitizer, the luminometric method can be used to reliably quantify aPDI effects in most of the analyzed bacterial strains. The interference of photosensitizers with the luminometric readout and the bioluminescence of some bacterial strains were identified as possible confounders. Using this method, we could confirm the susceptibility of several bacterial strains to photodynamic treatment, including extensively drug-resistant pathogens (XDR). In contrast to the conventional culture-based determination of bacterial density, the luminometric assay allowed for a much more time-effective analysis of various treatment conditions. We recommend this luminometric method for high-throughput tasks requiring measurements of bacterial viability in the context of photodynamic treatment approaches. Full article
(This article belongs to the Special Issue Photodynamic Therapy: Applications against Microorganisms)
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17 pages, 2920 KiB  
Article
The Meta-Substituted Isomer of TMPyP Enables More Effective Photodynamic Bacterial Inactivation than Para-TMPyP In Vitro
by Sebastian Schulz, Svitlana Ziganshyna, Norman Lippmann, Sarah Glass, Volker Eulenburg, Natalia Habermann, Ulrich T. Schwarz, Alexander Voigt, Claudia Heilmann, Tobias Rüffer and Robert Werdehausen
Microorganisms 2022, 10(5), 858; https://doi.org/10.3390/microorganisms10050858 - 21 Apr 2022
Cited by 7 | Viewed by 2863
Abstract
Porphyrinoid-based photodynamic inactivation (PDI) provides a promising approach to treating multidrug-resistant infections. However, available agents for PDI still have optimization potential with regard to effectiveness, toxicology, chemical stability, and solubility. The currently available photosensitizer TMPyP is provided with a para substitution pattern ( [...] Read more.
Porphyrinoid-based photodynamic inactivation (PDI) provides a promising approach to treating multidrug-resistant infections. However, available agents for PDI still have optimization potential with regard to effectiveness, toxicology, chemical stability, and solubility. The currently available photosensitizer TMPyP is provided with a para substitution pattern (para-TMPyP) of the pyridinium groups and has been demonstrated to be effective for PDI of multidrug-resistant bacteria. To further improve its properties, we synthetized a structural variant of TMPyP with an isomeric substitution pattern in a meta configuration (meta-TMPyP), confirmed the correct structure by crystallographic analysis and performed a characterization with NMR-, UV/Vis-, and IR spectroscopy, photostability, and singlet oxygen generation assay. Meta-TMPyP had a hypochromic shift in absorbance (4 nm) with a 55% higher extinction coefficient and slightly improved photostability (+6.9%) compared to para-TMPyP. Despite these superior molecular properties, singlet oxygen generation was increased by only 5.4%. In contrast, PDI, based on meta-TMPyP, reduced the density of extended spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli by several orders of magnitude, whereby a sterilizing effect was observed after 48 min of illumination, while para-TMPyP was less effective (p < 0.01). These findings demonstrate that structural modification with meta substitution increases antibacterial properties of TMPyP in PDI. Full article
(This article belongs to the Special Issue Photodynamic Therapy: Applications against Microorganisms)
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14 pages, 2248 KiB  
Article
The Antimicrobial Photoinactivation Effect on Escherichia coli through the Action of Inverted Cationic Porphyrin–Cyclodextrin Conjugates
by Cláudia P. S. Ribeiro, Maria A. F. Faustino, Adelaide Almeida and Leandro M. O. Lourenço
Microorganisms 2022, 10(4), 718; https://doi.org/10.3390/microorganisms10040718 - 26 Mar 2022
Cited by 13 | Viewed by 2407
Abstract
Photodynamic action has been used for diverse biomedical applications, such as treating a broad range of bacterial infections. Based on the combination of light, dioxygen, and photosensitizer (PS), the photodynamic inactivation (PDI) approach led to the formation of reactive oxygen species (ROS) and [...] Read more.
Photodynamic action has been used for diverse biomedical applications, such as treating a broad range of bacterial infections. Based on the combination of light, dioxygen, and photosensitizer (PS), the photodynamic inactivation (PDI) approach led to the formation of reactive oxygen species (ROS) and represented a non-invasive, non-toxic, repeatable procedure for pathogen photoinactivation. To this end, different tetrapyrrolic macrocycles, such as porphyrin (Por) dyes, have been used as PSs for PDI against microorganisms, mainly bacteria. Still, there is significant room for improvement, especially new PS molecules. Herein, unsymmetrical new pyridinone (3–5) and thiopyridyl Pors (7) were prepared with α-, β-, or γ-cyclodextrin (CD) units, following their quaternization to perform the corresponding free-base Pors (3a–5a and 7a), and were compared with the already-known Pors 6a and 8a, both bearing thiopyridinium and CD units. These water-soluble porphyrins were evaluated as PSs, and their photophysical and photochemical properties and photodynamic effects on E. coli were assessed. The presence of one CD unit and three positive charges on the Por structure (3a–5a and 7a) enhanced their aqueous solubility. The photoactivity of the cationic Pors 3a–5a and 6a–8a ensured their potential against the Gram-negative bacterium E. coli. Within each series of methoxypyridinium vs thiopyridinium dyes, the best PDI efficiency was achieved for 5a with a bacterial viability reduction of 3.5 log10 (50 mW cm−2, 60 min of light irradiation) and for 8a with a total bacterial viability reduction (>8 log10, 25 mW cm−2, 30 min of light irradiation). Here, the presence of the methoxypyridinium units is less effective against E. coli when compared with the thiopyridinium moieties. This study allows for the conclusion that the peripheral charge position, quaternized substituent type/CD unit, and affinity to the outer bacterial structures play an important role in the photoinactivation efficiency of E. coli, evidencing that these features should be further addressed in the pursuit for optimised PS for the antimicrobial PDI of pathogenic microorganisms. Full article
(This article belongs to the Special Issue Photodynamic Therapy: Applications against Microorganisms)
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13 pages, 4470 KiB  
Article
Inactivation of Opportunistic Pathogens Acinetobacter baumannii and Stenotrophomonas maltophilia by Antimicrobial Photodynamic Therapy
by Irina Buchovec, Laurita Klimkaitė, Edita Sužiedėlienė and Saulius Bagdonas
Microorganisms 2022, 10(3), 506; https://doi.org/10.3390/microorganisms10030506 - 25 Feb 2022
Cited by 11 | Viewed by 2771
Abstract
Acinetobacter baumannii and Stenotrophomonas maltophilia are opportunistic pathogens causing hospital infections with limited treatment options due to bacterial multidrug resistance. Here, we report that antimicrobial photodynamic therapy (aPDT) based on the natural photosensitizers riboflavin and chlorophyllin inactivates A. baumannii and S. maltophilia. [...] Read more.
Acinetobacter baumannii and Stenotrophomonas maltophilia are opportunistic pathogens causing hospital infections with limited treatment options due to bacterial multidrug resistance. Here, we report that antimicrobial photodynamic therapy (aPDT) based on the natural photosensitizers riboflavin and chlorophyllin inactivates A. baumannii and S. maltophilia. The riboflavin and chlorophyllin photostability experiments assessed the photomodifications of photosensitizers under the conditions subsequently used to inactivate A. baumannii and S. maltophilia. A. baumannii planktonic cells were more sensitive to riboflavin-aPDT, while biofilm bacteria were more efficiently inactivated by chlorophyllin-aPDT. S. maltophilia planktonic and biofilm cells were more susceptible to chlorophyllin-aPDT compared to riboflavin-aPDT. The results suggest that riboflavin- and chlorophyllin-aPDT can be considered as a potential antimicrobial treatment for A. baumannii and S. maltophilia inactivation. Full article
(This article belongs to the Special Issue Photodynamic Therapy: Applications against Microorganisms)
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