Simultaneous exposure to intracellular and extracellular photosensitizers for the treatment of Staphylococcus aureus infections

2021 ◽  
Author(s):  
Sydney L. Drury ◽  
Anderson R. Miller ◽  
Clare L. Laut ◽  
Alec B. Walter ◽  
Monique R. Bennett ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Near Infrared ◽  
Antimicrobial Photodynamic Therapy ◽  
Biological Processes ◽  
Drug Resistant ◽  
Soft Tissue Infections ◽  
Positive Bacterium ◽  
Human Monoclonal Antibodies ◽  
Simultaneous Exposure

Staphylococcus aureus is a serious threat to public health due to the rise of antibiotic resistance in this organism, which can prolong or exacerbate skin and soft tissue infections (SSTIs). Methicillin-resistant S. aureus is a Gram-positive bacterium and a leading cause of SSTIs. As such, many efforts are underway to develop therapies that target essential biological processes in S. aureus . Antimicrobial photodynamic therapy is effective alternative to antibiotics, therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photoactivators. A near infrared photosensitizer was conjugated to human monoclonal antibodies (mAbs) that target the S. aureus Isd heme acquisition proteins. Additionally, the compound VU0038882 was developed to increase photoactivatable porphyrins within the cell. Combinatorial PDT treatment of drug-resistant S. aureus exposed to VU0038882 and conjugated anti-Isd mAbs proved to be an effective antibacterial strategy in vitro and in a murine model of SSTIs.

scholarly journals Efficiency of Antimicrobial Photodynamic Therapy with Photodithazine® on MSSA and MRSA Strains

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 869
Author(s):  
Beatriz Müller Nunes Souza ◽  
Juliana Guerra Pinto ◽  
André Henrique Correia Pereira ◽  
Alejandro Guillermo Miñán ◽  
Juliana Ferreira-Strixino
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
Antimicrobial Photodynamic Therapy ◽  
Bacterial Inactivation ◽  
Bacterial Reduction ◽  
Complete Inactivation ◽  
Opportunistic Bacteria ◽  
Significant Difference ◽  
Mrsa Strains

Staphylococccus aureus is a ubiquitous and opportunistic bacteria associated with high mortality rates. Antimicrobial photodynamic therapy (aPDT) is based on the application of a light source and a photosensitizer that can interact with molecular oxygen, forming Reactive Oxygen Species (ROS) that result in bacterial inactivation. This study aimed to analyze, in vitro, the action of aPDT with Photodithazine® (PDZ) in methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains. The strains were incubated with PDZ at 25, 50, 75, and 100 mg/L for 15 min and irradiated with fluences of 25, 50, and 100 J/cm2. The internalization of PDZ was evaluated by confocal microscopy, the bacterial growth by counting the number of colony-forming units, as well as the bacterial metabolic activity post-aPDT and the production of ROS. In both strains, the photosensitizer was internalized; the production of ROS increased when the aPDT was applied; there was a bacterial reduction compared to the control at all the evaluated fluences and concentrations; and, in most parameters, it was obtained complete inactivation with significant difference (p < 0.05). The implementation of aPDT with PDZ in clinical strains of S. aureus has resulted in its complete inactivation, including the MRSA strains.

Antimicrobial photodynamic therapy in chronic osteomyelitis induced by Staphylococcus aureus: An in vitro and in vivo study

2012 ◽  
Author(s):  
João Alves dos Reis Júnior ◽  
Patrícia Nascimento de Assis ◽  
Garde^nia Matos Paraguassú ◽  
Isabele Cardoso Vieira de de Castro ◽  
Renan Ferreira Trindade ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Photodynamic Therapy ◽  
Chronic Osteomyelitis ◽  
In Vivo Study ◽  
Antimicrobial Photodynamic Therapy

scholarly journals The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy Against Staphylococcus aureus

2020 ◽  
Vol 21 (24) ◽  
pp. 9410
Author(s):  
Bruno Casciaro ◽  
Maria Rosa Loffredo ◽  
Floriana Cappiello ◽  
Guendalina Fabiano ◽  
Luisa Torrini ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Keratinocytes ◽  
Skin Infections ◽  
Positive Bacterium ◽  
Persister Cells ◽  
Dividing Cells ◽  
Adverse Environmental Conditions ◽  
Bacterial Skin Infections ◽  
First Time

Bacterial biofilms are a serious threat for human health, and the Gram-positive bacterium Staphylococcus aureus is one of the microorganisms that can easily switch from a planktonic to a sessile lifestyle, providing protection from a large variety of adverse environmental conditions. Dormant non-dividing cells with low metabolic activity, named persisters, are tolerant to antibiotic treatment and are the principal cause of recalcitrant and resistant infections, including skin infections. Antimicrobial peptides (AMPs) hold promise as new anti-infective agents to treat such infections. Here for the first time, we investigated the activity of the frog-skin AMP temporin G (TG) against preformed S. aureus biofilm including persisters, as well as its efficacy in combination with tobramycin, in inhibiting S. aureus growth. TG was found to provoke ~50 to 100% reduction of biofilm viability in the concentration range from 12.5 to 100 µM vs ATCC and clinical isolates and to be active against persister cells (about 70–80% killing at 50–100 µM). Notably, sub-inhibitory concentrations of TG in combination with tobramycin were able to significantly reduce S. aureus growth, potentiating the antibiotic power. No critical cytotoxicity was detected when TG was tested in vitro up to 100 µM against human keratinocytes, confirming its safety profile for the development of a new potential anti-infective drug, especially for treatment of bacterial skin infections.

In vitro antimicrobial activity of nanoconjugated vancomycin against drug resistant Staphylococcus aureus

2012 ◽  
Vol 436 (1-2) ◽  
pp. 659-676 ◽  
Author(s):  
Subhankari Prasad Chakraborty ◽  
Sumanta Kumar Sahu ◽  
Panchanan Pramanik ◽  
Somenath Roy
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Drug Resistant ◽  
In Vitro Antimicrobial Activity

scholarly journals ANTIBACTERIAL PHOTODYNAMIC THERAPEUTIC STUDIES OF METALLATED PORPHYRIN AGAINST CHRONIC WOUND COLONISING BACTERIAL ISOLATES

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
O. B Daramola ◽  
A. A Olajide ◽  
N Torimiro ◽  
R. C George
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Chronic Wound ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
In Vitro Toxicity ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Bacterial Strains

Wound infections have become life threatening as a result of treatment failures caused by multi-drug resistant pathogens. The search for newer compounds potent against antibiotic resistant bacteria associated with wounds is crucial. Hence this study investigated the application of antibacterial photodynamic therapy using meso tetra-(4-phenyl) porphyrin (TPP), metallated with zinc, tin and silver (ZnTPP, SnTPP and AgTPP), meso tetra-(4-sulphonatephenyl) porphyrin (TPPS) and the corresponding metallo meso tetra-(4-sulphonatephenyl) porphyrin (MTPPS) as photosensitizers. The in-vitro toxicity and photo-toxicity properties on four chronic wound colonizing multi-drug resistant bacterial strains: Staphylococcus aureus, Klebsiella sp., Proteus sp., and Escherichia coli were assessed using agar well diffusion method. Photo-toxicity of the compounds was investigated using 100 Watt tungsten lamp. Inhibitory activity of porphyrins tested against these bacterial strains showed Staphylococcus aureus to have both lowest (11±0.0 mm) and highest (33±1.1 mm) susceptibility to SnTPPS and ZnTPPS respectively. The sequence of data also showed appreciable improvement in the antimicrobial activities of five metalloporphyrins (SnTPP, AgTPP, ZnTPPS, SnTPPS and AgTPPS) exposed to light rays than when tested against bacterial strains in dark condition. ZnTPPS exhibited the best activity with improved photo-toxic activities against all bacterial strains (Staphylococcus aureus 33±1.1 mm, Klebsiella sp. 32±0.7 mm, Proteus sp. 28±0.7 mm and Escherichia coli 30±1.4 mm) examined in this study.

scholarly journals The Combined Antibacterial Effects of Sodium New Houttuyfonate and Berberine Chloride against Growing and Persistent Methicillin-Resistant and Vancomycin-Intermediate Staphylococcus aureus

2020 ◽  
Author(s):  
Xue Li ◽  
Penghe Wang ◽  
Xinxin Hu ◽  
Youwen Zhang ◽  
Xi Lu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Action ◽  
Clinical Use ◽  
Drug Resistant ◽  
Antibacterial Effects ◽  
Persister Cells ◽  
Berberine Chloride ◽  
Combined Use ◽  
Scanning Electron

Abstract Background: Infections caused by drug-resistant Staphylococcus aureus, especially vancomycin-intermediate Staphylococcus aureus (VISA), leave clinicians with limited therapeutic options for treatment. Persister cells is a leading cause of recalcitrant infection and antibiotic treatment failure, and there is no drug in clinical use that specifically targets persister cells currently. Here, we report a promising combination therapy of sodium new houttuyfonate (SNH) and berberine chloride (BBR) which is able to eradicate both growing and persistent drug-resistant Staphylococcus aureus.Results: The susceptibility test showed SNH exhibited anti-MRSA activity with MIC90 at 64 μg/mL, while BBR showed weak anti-MRSA activity with MIC90 at 512 μg/mL. MICs of BBR in combination with 1/2 MIC SNH decreased by 4 to 64 folds compared with MICs of BBR alone. The results of time-killing assays revealed that the combined use of sub-MIC SNH and BBR offered an in vitro synergistic action against growing MRSA (including pathogenic MRSA) and VISA strains. More importantly, the combination of SNH and BBR was able to eradicate VISA Mu50 and pathogenic MRSA persister cells. The synergistic effect is likely related to the interruption of the cell membrane caused by SNH, which is confirmed by scanning electron microscope and membrane potential and permeability analysis.Conclusions: Our study provide a promising clinical curative strategy for combating drug-resistant S. aureus infections, especially for recalcitrant infections caused by persister cells.

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