Biological properties of polyoxometalates against bacterial antibiotic resistance

• Main Author: Almas, Sadaf
• Publication Date: 2023
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10400.1/25685
• topic: Antibiotic Resistance; Antibacterial Strategies; Medicines; Non-Antibiotic

The current study addresses the urgent problem of antibiotic resistance and investigates the potential of metal-based compounds as antibacterial agents to combat important bacterial pathogens. Five Polyoxometalates (POMs), Mo17V3, PV2Mo12, Mo10V2, Co(pyz)V10, Co(nic)V10 and one metal complex V5P4O35C14N6H52, were examined for antibacterial activity, yet none exhibited any antibacterial effects against Staphylococcus aureus ATCC6538 and Escherichia coli DSM1077. The research also explored the osmotolerance of the methicillin susceptible S. aureus ATCC 6538 and the methicillin resistant S. aureus (MRSA16) in response to different NaCl concentrations. Both S. aureus strains demonstrated dose-dependent responses to salt, with increased susceptibility at 1.5%, 3%, and 4% salt concentrations, elevated susceptibility at 7%. These findings shed light on how S. aureus strains adapt to salt stress and its potential implications for antibiotic resistance and growth kinetics. The antimicrobial properties of P5W30 Preyssler-type polyoxometalates in combination with varying NaCl concentrations revealed that P5W30 effectively inhibits S. aureus ATCC 6538, with a MIC of 32 μM, and MRSA16, with a MIC of 600 μM. These findings provide insights into P5W30 potential for inhibiting bacterial growth and its interactions with salinity. The study also assessed the impact of salt and P5W30 on virulence using Galleria mellonella larvae as an infection model against S. aureus ATCC 6538. The results showed that while larvae injected with control bacterial culture alone experienced a significant decrease in survival over five days (6.7% survival), in contrast the exposure of bacterials cells to the MIC value of P5W30 (32 μM) enhanced the survival of larvae, reaching 26.7% by day-5. Furthermore, the research explored the inhibitory properties of Mo17V3, a molybdenum-based polyoxometalate (POMo), on Ca2+ -ATPase enzymes, with a specific focus on sarcoplasmic reticulum calcium ATPase (SERCA). It successfully determined an IC50 value of approximately 1.84 μM, demonstrating its superior inhibitory efficiency. The stability of Mo17V3 in experimental conditions, revealing its instability during a 2 hrs incubation at room temperature, potentially due to speciation or decomposition. A key point is Mo17V3 acts as a mixed-type inhibitor of SERCA, indicating direct binding and an impact on enzyme activity and indicating Mo17V3 as a promising mixed-type inhibitor of SERCA and highlights its potential in diverse biomedical applications.