scholarly journals Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1399
Author(s):  
Ben Chung Lap Chan ◽  
Priyanga Dharmaratne ◽  
Baiyan Wang ◽  
Kit Man Lau ◽  
Ching Ching Lee ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Infection Model ◽  
Wound Infections ◽  
Pheophorbide A ◽  
Promising Alternative ◽  
Translational Study ◽  
Therapeutic Modalities ◽  
High Prevalence

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.

scholarly journals Quinine Enhances Photo-Inactivation of Gram-Negative Bacteria

2019 ◽  
Vol 221 (4) ◽  
pp. 618-626 ◽  
Author(s):  
Leon G Leanse ◽  
Pu-Ting Dong ◽  
Xueping S Goh ◽  
Min Lu ◽  
Ji-Xin Cheng ◽  
...  
Keyword(s):  
Mouse Skin ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Antimicrobial Effects ◽  
Therapeutic Modalities ◽  
Novel Approach

Abstract Background Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. Methods In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. Results Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. Conclusions In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light

1991 ◽  
Vol 11 (2) ◽  
pp. 174-182 ◽  
Author(s):  
Takashi Yano ◽  
Tohru Uozumi ◽  
Keiichi Kawamoto ◽  
Kazutoshi Mukada ◽  
Jun Onda ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
White Light ◽  
Pituitary Tumor ◽  
Pheophorbide A ◽  
Rat Pituitary

Photodynamic Therapy of Pheophorbide a Inhibits the Proliferation of Human Breast Tumour via Both Caspase-dependent and -independent Apoptotic Pathways in In Vitro and In Vivo Models

2011 ◽  
Vol 26 (5) ◽  
pp. 734-742 ◽  
Author(s):  
Sandy Wan-Heng Hoi ◽  
Hoi Ming Wong ◽  
Judy Yuet-Wa Chan ◽  
Grace Gar Lee Yue ◽  
Gary Man-Kit Tse ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Breast Tumour ◽  
Human Breast ◽  
Pheophorbide A ◽  
In Vivo Models ◽  
Human Breast Tumour ◽  
Apoptotic Pathways

scholarly journals Tetradecanoic Acids With Anti-Virulence Properties Increase the Pathogenicity of Pseudomonas aeruginosa in a Murine Cutaneous Infection Model

2021 ◽  
Vol 10 ◽  
Author(s):  
Martha María Juárez-Rodríguez ◽  
Humberto Cortes-López ◽  
Rodolfo García-Contreras ◽  
Bertha González-Pedrajo ◽  
Miguel Díaz-Guerrero ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Infection Model ◽  
Cutaneous Infection ◽  
Complex Environments ◽  
Promising Alternative ◽  
Virulence Target

Blocking virulence is a promising alternative to counteract Pseudomonas aeruginosa infections. In this regard, the phenomenon of cell-cell communication by quorum sensing (QS) is an important anti-virulence target. In this field, fatty acids (FA) have gained notoriety for their role as autoinducers, as well as anti-virulence molecules in vitro, like some saturated FA (SAFA). In this study, we analyzed the anti-virulence activity of SAFA with 12 to18 carbon atoms and compared their effect with the putative autoinducer cis-2-decenoic acid (CDA). The effect of SAFA on six QS-regulated virulence factors and on the secretion of the exoenzyme ExoU was evaluated. In addition, a murine cutaneous infection model was used to determine their influence on the establishment and damage caused by P. aeruginosa PA14. Dodecanoic (lauric, C12:0) and tetradecanoic (myristic, C14:0) acids (SAFA C12-14) reduced the production of pyocyanin by 35–58% at 40 and 1,000 µM, while CDA inhibited it 62% at a 3.1 µM concentration. Moreover, the SAFA C12-14 reduced swarming by 90% without affecting biofilm formation. In contrast, CDA reduced the biofilm by 57% at 3 µM but did not affect swarming. Furthermore, lauric and myristic acids abolished ExoU secretion at 100 and 50 µM respectively, while CDA reduced it by ≈ 92% at 100 µM. Remarkably, the coadministration of myristic acid (200 and 1,000 µM) with P. aeruginosa PA14 induced greater damage and reduced survival of the animals up to 50%, whereas CDA to 500 µM reduced the damage without affecting the viability of the PA14 strain. Hence, our results show that SAFA C12-14 and CDA have a role in regulation of P. aeruginosa virulence, although their inhibition/activation molecular mechanisms are different in complex environments such as in vivo systems.

scholarly journals Phages from Ganges River curtail in vitro biofilms and planktonic growth of drug resistant Klebsiella pneumoniae in a zebrafish infection model

2020 ◽  
Author(s):  
Niranjana Sri Sundaramoor ◽  
Subramanian Thothathri ◽  
Muthu Meenakshi Bhaskaran ◽  
ArunKumar GaneshPrasad ◽  
Saisubramanian Nagarajan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Infection Model ◽  
Histopathological Analysis ◽  
Drug Resistant ◽  
Ganges River ◽  
Promising Alternative ◽  
Planktonic Growth ◽  
Time Kill

Abstract Bacteriophages are a promising alternative for curtailing infections caused by multi drug resistant (MDR) bacteria. The objective of the present study is to evaluate phage populations from water bodies to inhibit planktonic and biofilm mode of growth of drug resistant Klebsiella pneumoniae in vitro and curtail planktonic growth in vivo in a zebrafish model. Phage specific to K. pneumoniae (MTCC 432) was isolated from Ganges river (designated as KpG). One-step growth curve, in vitro time kill curve study and in vivo infection model were performed to evaluate the efficacy of phage to curtail planktonic growth. Crystal violet assay and colony biofilm assay was done to determine the action of phages on biofilms. KpG phages had a greater burst size, better bactericidal potential and enhanced inhibitory effect against biofilms formed at liquid air and solid air interfaces. In vivo injection of KpG phages revealed that it did not pose any toxicity to zebrafish as evidenced by liver/brain enzyme profiles and by histopathological analysis. In vitro time kill assay showed a 3 log decline and a 6 log decline in K. pneumoniae colony counts, when phages were administered individually and in combination with streptomycin, respectively. The muscle tissue of zebrafish, infected with K. pneumoniae and treated with KpG phages showed a significant 2 log decline in bacterial counts relative to untreated control. Our study reveals that KpG phages has the potential to curtail plantonic and biofilm mode of growth in vivo in higher animal models.

scholarly journals Phages from Ganges River curtail in vitro biofilms and planktonic growth of drug resistant Klebsiella pneumoniae in a zebrafish infection model

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niranjana Sri Sundaramoorthy ◽  
Subramaniam Thothathri ◽  
Muthumeenakshi Bhaskaran ◽  
ArunKumar GaneshPrasad ◽  
Saisubramanian Nagarajan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Infection Model ◽  
Histopathological Analysis ◽  
Drug Resistant ◽  
Ganges River ◽  
Promising Alternative ◽  
Planktonic Growth ◽  
Time Kill

AbstractBacteriophages are a promising alternative for curtailing infections caused by multi drug resistant (MDR) bacteria. The objective of the present study is to evaluate phage populations from water bodies to inhibit planktonic and biofilm mode of growth of drug resistant Klebsiella pneumoniae in vitro and curtail planktonic growth in vivo in a zebrafish model. Phage specific to K. pneumoniae (MTCC 432) was isolated from Ganges River (designated as KpG). One-step growth curve, in vitro time kill curve study and in vivo infection model were performed to evaluate the ability of phage to curtail planktonic growth. Crystal violet assay and colony biofilm assay were performed to determine the action of phages on biofilms. KpG phages had a greater burst size, better bactericidal potential and enhanced inhibitory effect against biofilms formed at liquid air and solid air interfaces. In vitro time kill assay showed a 3 log decline and a 6 log decline in K. pneumoniae colony counts, when phages were administered individually and in combination with streptomycin, respectively. In vivo injection of KpG phages revealed that it did not pose any toxicity to zebrafish as evidenced by liver/brain enzyme profiles and by histopathological analysis. The muscle tissue of zebrafish, infected with K. pneumoniae and treated with KpG phages alone and in combination with streptomycin showed a significant 77.7% and 97.2% decline in CFU/ml, respectively, relative to untreated control. Our study reveals that KpG phages has the potential to curtail plantonic and biofilm mode of growth in higher animal models.

scholarly journals Phages from Ganges River curtail in vitro biofilms and planktonic growth of drug resistant Klebsiella pneumoniae in a zebrafish infection model

2020 ◽  
Author(s):  
Niranjana Sri Sundaramoor ◽  
Subramanian Thothathri ◽  
Muthu Meenakshi Bhaskaran ◽  
ArunKumar GaneshPrasad ◽  
Saisubramanian Nagarajan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Infection Model ◽  
Histopathological Analysis ◽  
Drug Resistant ◽  
Ganges River ◽  
Promising Alternative ◽  
Planktonic Growth ◽  
Time Kill

Abstract Bacteriophages are a promising alternative for curtailing infections caused by multi drug resistant (MDR) bacteria. The objective of the present study is to evaluate phage populations from water bodies to inhibit planktonic and biofilm mode of growth of drug resistant Klebsiella pneumoniae in vitro and curtail planktonic growth in vivo in a zebrafish model. Phage specific to K. pneumoniae (MTCC 432) was isolated from Ganges river (designated as KpG). One-step growth curve, in vitro time kill curve study and in vivo infection model were performed to evaluate the efficacy of phage against planktonic growth. Crystal violet assay and colony biofilm assay was done to determine the action of phages on biofilms. KpG phages had a greater burst size, better bactericidal potential and enhanced inhibitory effect against biofilms formed at liquid air and solid air interfaces. In vivo injection of KpG phages revealed that it did not pose any toxicity to zebrafish as evidenced by liver/brain enzyme profiles and by histopathological analysis. In vitro time kill assay showed a 3 log decline and a 6 log decline in K. pneumoniae colony counts, when phages were administered individually and in combination with streptomycin, respectively. The muscle tissue of zebrafish, infected with K. pneumoniae and treated with KpG phages showed a significant 2 log decline in bacterial counts relative to untreated control. Our study reveals that KpG phages has the potential to curtail plantonic and biofilm mode of growth in vivo in higher animal models.

scholarly journals Phages from Ganges River curtail in vitro biofilms and planktonic growth of drug resistant Klebsiella pneumoniae in a zebrafish infection model

2021 ◽  
Author(s):  
Niranjana Sri Sundaramoor ◽  
Subramanian Thothathri ◽  
Muthu Meenakshi Bhaskaran ◽  
ArunKumar GaneshPrasad ◽  
Saisubramanian Nagarajan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Infection Model ◽  
Histopathological Analysis ◽  
Drug Resistant ◽  
Ganges River ◽  
Promising Alternative ◽  
Planktonic Growth ◽  
Time Kill

Abstract Bacteriophages are a promising alternative for curtailing infections caused by multi drug resistant (MDR) bacteria. The objective of the present study is to evaluate phage populations from water bodies to inhibit planktonic and biofilm mode of growth of drug resistant Klebsiella pneumoniae in vitro and curtail planktonic growth in vivo in a zebrafish model. Phage specific to K. pneumoniae (MTCC 432) was isolated from Ganges River (designated as KpG). One-step growth curve, in vitro time kill curve study and in vivo infection model were performed to evaluate the ability of phage to curtail planktonic growth. Crystal violet assay and colony biofilm assay were performed to determine the action of phages on biofilms. KpG phages had a greater burst size, better bactericidal potential and enhanced inhibitory effect against biofilms formed at liquid air and solid air interfaces. In vitro time kill assay showed a 3 log decline and a 6 log decline in K. pneumoniae colony counts, when phages were administered individually and in combination with streptomycin, respectively. In vivo injection of KpG phages revealed that it did not pose any toxicity to zebrafish as evidenced by liver/brain enzyme profiles and by histopathological analysis. The muscle tissue of zebrafish, infected with K. pneumoniae and treated with KpG phages alone and in combination with streptomycin showed a significant 77.7% and 97.2 % decline in CFU/ml, respectively, relative to untreated control. Our study reveals that KpG phages has the potential to curtail plantonic and biofilm mode of growth in vivo in higher animal models.

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