Metalloporphyrin-based photodynamic inactivation of multidrug-resistant environmental mastitis pathogens

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.