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Metalloporphyrin-based photodynamic inactivation of multidrug-resistant environmental mastitis pathogens
Luiz Henrique Barbosa Pires1, Ana Carolina Borsanelli1, Leonardo Pereira Franchi2
1Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, GO, Brazil.
Abstract:
Bacteria such as Klebsiella pneumoniae, Proteus mirabilis and Streptococcus dysgalactiae are often associated with environmental and zoonotic agents causing bovine mastitis. In addition, the emergence of multidrug-resistant (MDR) strains associated with these pathogens poses a significant challenge to the effectiveness of conventional antimicrobial therapies. Thus, this study aimed to evaluate the efficacy of antimicrobial photodynamic inactivation (aPDI) as an alternative for controlling environmental pathogens related to mastitis. Four meso-Tetra-(4-pyridyl)porphyrin/palladium(II) complexes (DPPE, DPPP, DPPB, and DPPF) were used as photosensitizers (PS) against clinical isolates of K. pneumoniae, P. mirabilis, and S. dysgalactiae. Here DPPE, DPPP, DPPB, and DPPF refer to the diphosphine present in the Pd(II) complex (DPPE = . 1,2-bis(diphenylphosphino)ethane; DPPP = 1,3-bis(diphenylphosphino)propane; DPPB = 1,4-bis(diphenylphosphino)butane; DPPF = 1,1'-bis(diphenylphosphino)ferrocene. Antimicrobial susceptibility testing confirmed concerning MDR profiles in P. mirabilis and K. pneumoniae. The aPDI assessments revealed that DPPE, DPPP, and DPPB exhibited a minimum effective concentration (MEC) of 1.56 μM against S. dysgalactiae. For P. mirabilis, the MECs determined were 12.5 μM for DPPP and 100 μM for DPPF. In contrast, against K. pneumoniae, only two PSs exhibited significant activity, with MEC values of 3.12 μM for DPPP and 25 μM for DPPF. In the time kill kinetics assay, the photodynamic activity of the PS DPPP was particularly remarkable, as it effectively inhibited bacterial growth (MIC100) in all tested strains for up to 45 min irradiation. Moreover, the Ames mutagenicity assay revealed that none of the PSs exhibited significant mutagenic activity at the concentrations evaluated, thereby indicating a favorable safety profile. These findings highlight the potential of aPDI as a promising strategy for the control of MDR pathogens implicated in mastitis.
Insights
Antimicrobial photodynamic inactivation (aPDI) effectively controlled multidrug-resistant (MDR) bacteria causing bovine mastitis. Palladium(II) complexes showed potent antimicrobial activity with no significant mutagenicity, offering a promising alternative therapy.
Area of Science:
- Veterinary Medicine
- Photochemistry
- Antimicrobial Resistance
Background:
- Bovine mastitis is frequently caused by environmental and zoonotic bacteria like Klebsiella pneumoniae, Proteus mirabilis, and Streptococcus dysgalactiae.
- The rise of multidrug-resistant (MDR) strains among these pathogens complicates treatment and necessitates alternative therapeutic strategies.
- Antimicrobial photodynamic inactivation (aPDI) presents a potential alternative for controlling mastitis-causing pathogens.
Purpose of the Study:
- To evaluate the efficacy of four meso-Tetra-(4-pyridyl)porphyrin/palladium(II) complexes as photosensitizers (PS) for aPDI against clinical isolates of K. pneumoniae, P. mirabilis, and S. dysgalactiae.
- To assess the antimicrobial susceptibility and MDR profiles of the selected bacterial strains.
- To determine the safety profile of the photosensitizers using the Ames mutagenicity assay.
Main Methods:
- Four palladium(II) complexes (DPPE, DPPP, DPPB, DPPF) were employed as photosensitizers.
- Antimicrobial susceptibility testing was performed to identify MDR strains.
- aPDI efficacy was assessed by determining the minimum effective concentration (MEC) against bacterial isolates.
- Time kill kinetics assays were conducted to evaluate bacterial growth inhibition.
- The Ames mutagenicity assay was used to assess the safety of the photosensitizers.
Main Results:
- Antimicrobial susceptibility testing confirmed MDR profiles in P. mirabilis and K. pneumoniae.
- DPPE, DPPP, and DPPB showed a minimum effective concentration (MEC) of 1.56 μM against S. dysgalactiae.
- DPPP (12.5 μM) and DPPF (100 μM) were effective against P. mirabilis, while DPPP (3.12 μM) and DPPF (25 μM) showed activity against K. pneumoniae.
- The photosensitizer DPPP demonstrated significant bacterial growth inhibition for up to 45 minutes in time kill kinetics assays.
- None of the tested photosensitizers exhibited significant mutagenic activity.
Conclusions:
- aPDI using palladium(II) complexes is a promising strategy for controlling multidrug-resistant mastitis pathogens.
- The tested photosensitizers demonstrated potent antimicrobial activity and a favorable safety profile.
- This approach offers a potential alternative to conventional antimicrobial therapies for bovine mastitis.
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