Soong Wei Si

Soong Wei Si

Sunway University | | Degree: Biomedicine
Evaluation of Antibacterial Activity of Phosphanegold(I) Thiolate Compounds on Methicillin Resistant-Staphylococcus aureus (MRSA)
  • Antimicrobial resistance (AMR) is considered as one of the leading health threats in the public. 
  • AMR happens when the drug becomes ineffective or less effective against the bacterial infections due to the rapid change in permeability, enzyme modification or alteration in the target site of bacteria. 
  • According to the WHO (2017), methicillin-resistant Staphylococcus aureus (MRSA) is classified as one of the high-priority pathogens that require urgent counteraction with novel antibiotics.

Phosphanegold(I) thiolate compounds

  • Structurally mimic auranofin
  • Phosphine and thiolate ligand bind to the gold centre
  • Inhibit thioredoxin reductase enzyme in MRSA

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  • To study the antibacterial activity of phosphanegold(I) thiolate compounds on MRSA.
  • To investigate the synergistic effect of phosphanegold(I) thiolate compounds with chloramphenicol against MRSA.

Chloramphenicol

  • Effectively inhibit MRSA growth.
  • Blocking protein synthesis.
  • Cause dose-related bone marrow suppression.

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  • Phosphanegold(I) thiolate compounds (AAu1-3 compounds), chloramphenicol and gold precursor were potent against MRSA with the MIC values found to be 3.125-6.25 µg/mL, 6.25 µg/mL and 6.25 µg/mL, respectively. 
  • The MBC/MIC values of less than or equal 4 indicated that these compounds were bactericidal and worked well in killing the MRSA population. 
  • In contrast, MRSA was not susceptible to thiolate ligands (L1-3) as the bacterial growth could be observed at all the concentrations tested, thus the MIC and MBC values were more than 100µg/mL.

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  • Antibacterial effect of the compounds was strongly associated with the gold centre in the compounds.
  • Precursor that does not have the ligand structure, can still exhibit its antibacterial potential against MRSA.
  • Thiolate ligands that do not consist of the gold centre in their chemical structure, were inactive when tested on MRSA. 

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  • AAu1 and AAu3 compounds were more effective than AAu2.
  • They can inhibit MRSA growth at a lower concentration.
  • Variation in the R-groups might lead to a differential bioactivity in inhibiting the MRSA growth.  
  • Structure-activity relationships in the phosphanegold(I) thiolate compounds can be investigated in future.

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  • Phosphanegold(I) thiolate compounds + chloramphenicol did not significantly increase their inhibitory efficacy against MRSA.
  • The reason for the lack of positive interactions remains unclear. 
  • The presence of chloramphenicol led to a reduction in MIC values for the phosphanegold(I) thiolate compounds by at least one concentration.

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I would like to express my sincere gratitude to my supervisor, Assoc. Prof. Dr. Chew Jactty and Ms. Clariss Goh for their guidance and advices through the research. 

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Soong Wei Si

Sunway University | | Degree: Biomedicine
Evaluation of Antibacterial Activity of Phosphanegold(I) Thiolate Compounds on Methicillin Resistant-Staphylococcus aureus (MRSA)

Abstract

Antibiotic resistance frequently causes current treatment options to become ineffective against many bacteria. Thus, utilising gold complexes as antibacterial agents has been proposed. Nevertheless, these complexes such as gold(I) thiolates and their antibacterial effects are not well studied. Therefore, this study was undertaken to evaluate the antibacterial activity of phosphanegold(I) thiolate compounds with the general structure Ph3PAu[SC(OR)=NC6H5] with different R-groups of CH3 (AAu1), CH2CH3 (AAu2), and CH(CH3)2 (AAu3) as well as the synergistic effects between these compounds and chloramphenicol antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). Broth dilution assay was conducted to determine the minimum inhibitory concentration (MIC) of the tested compounds against MRSA. Then, the drug combination effects were investigated through a checkerboard assay using fractional inhibitory concentration (FIC) index calculations. Results showed that phosphanegold(I) thiolate compounds were potent against MRSA, where AAu1 and AAu3 (MIC=3.125µg/mL) had better antibacterial activities than AAu2 (MIC=6.25µg/mL). This suggested the variation in R-groups of AAu1-3 compounds may influence their antibacterial efficacy. However, the AAu1-3 compounds and chloramphenicol drug combinations manifested indifferent interactions (FICI=1.25-1.50). Notably, this study has demonstrated the undisguised bactericidal effects exhibited by phosphanegold(I) thiolate compounds against MRSA. Thus, the combination of these compounds with other antibiotics as a novel treatment for antibiotic-resistance bacterial infections can be further considered.

Soong Wei Si