Photodynamic inactivation of methicillin-resistant Staphylococcus aureus by indocyanine green and near infrared light

Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, how this treatment affects MRSA drug sensitivity remains unknown. The drug-sensitivity phenotypes, bacterial growth rate, and cell-wall thickness of three MRSA strains were analyzed after ICG-PDT. Drug-resistant gene expressions were determined by polymerase chain reaction (PCR) and quantitative reverse transcription (qRT)-PCR. Related protein expressions were examined with immunoblotting. Drug sensitivity was further evaluated in animal models. MRSA that survived the treatment grew faster, and the cell wall became thinner compared to parental cells. These cells became more sensitive to oxacillin, which was partly related to mecA complex gene deletion. Skin necrosis caused by ICG-PDT-treated MRSA infection was smaller and healed faster than that infected with parental cells. With oxacillin therapy, no bacteria could be isolated from mouse lung tissue infected with ICG-PDT-treated MRSA. ICG-PDT drives MRSA toward an oxacillin-sensitive phenotype. It has the potential to develop into an alternative or adjuvant clinical treatment against MRSA wound infections.

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Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers Against Methicillin-Resistant Staphylococcus aureus

Biomedicines ◽

10.3390/biomedicines8060140 ◽

2020 ◽

Vol 8 (6) ◽

pp. 140 ◽

Cited By ~ 1

Author(s):

Priyanga Dharmaratne ◽

Roy C. H. Wong ◽

Jun Wang ◽

Pui-Chi Lo ◽

Baiyan Wang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Near Infrared ◽

Methicillin Resistant Staphylococcus Aureus ◽

Resistance Mechanisms ◽

Infrared Light ◽

Methicillin Resistant ◽

Photodynamic Activity ◽

Boron Dipyrromethene ◽

Type Strains

A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound 5) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant Staphylococcus aureus (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6’)-APH(2”) and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The in vitro anti-MRSA activity of compound 5 was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50–100 µM. Compound 5 was significantly (p < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.

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Au–ZnO Conjugated Black Phosphorus as a Near-Infrared Light-Triggering and Recurrence-Suppressing Nanoantibiotic Platform against Staphylococcus aureus

Pharmaceutics ◽

10.3390/pharmaceutics13010052 ◽

2021 ◽

Vol 13 (1) ◽

pp. 52

Author(s):

Atanu Naskar ◽

Sohee Lee ◽

Kwang-sun Kim

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Infections ◽

Near Infrared ◽

Au Nanoparticles ◽

Synthesis Method ◽

Antibacterial Properties ◽

Black Phosphorus ◽

Infrared Light ◽

Resistant Bacteria ◽

Near Infrared Light

Antibiotic therapy is the gold standard for bacterial infections treatment. However, the rapid increase in multidrug-resistant (MDR) bacterial infections and its recent use for secondary bacterial infections in many COVID-19 patients has considerably weakened its treatment efficacy. These shortcomings motivated researchers to develop new antibacterial materials, such as nanoparticle-based antibacterial platform with the ability to increase the chances of killing MDR strains and prevent their drug resistance. Herein, we report a new black phosphorus (BP)-based non-damaging near-infrared light-responsive platform conjugated with ZnO and Au nanoparticles as a synergistic antibacterial agent against Staphylococcus aureus species. First, BP nanosheets containing Au nanoparticles were assembled in situ with the ZnO nanoparticles prepared by a low-temperature solution synthesis method. Subsequently, the antibacterial activities of the resulting Au–ZnO–BP nanocomposite against the non-resistant, methicillin-resistant, and erythromycin-resistant S. aureus species were determined, after its photothermal efficacy was assessed. The synthesized nanocomposite exhibited excellent anti-S. aureus activity and good photothermal characteristics. The non-resistant S. aureus species did not produce drug-resistant bacteria after the treatment of multiple consecutive passages under the pressure of the proposed nanoantibiotic, but rapidly developed resistance to erythromycin. This work clearly demonstrates the excellent photothermal antibacterial properties of Au–ZnO–BP nanocomposite against the MDR S. aureus species.

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