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Research
Combating the melioidosis pathogen using antibiotics in combination with silver nanoparticles
Rina Patramanon
Khon Kaen University Faculty of Science
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9325-2527
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Melioidosis is an infectious disease caused by the Gram-negative bacillus bacterium, Burkholderia pseudomallei. Due to the emerging resistance of B. pseudomallei to antibiotics, including ceftazidime (CAZ), the development of novel antibiotics and alternative modes of treatment has become an urgent issue. Here, we demonstrate an ability to synergistically increase the efficiency of antibiotics through their combination with silver nanoparticles (AgNPs).
Method:
Combinations of four conventional antibiotics, including CAZ, imipenem (IMI), meropenem (MER), or gentamicin sulfate (GENT), with AgNPs were tested for their bactericidal effects against three isolates of B. pseudomallei, including 1026b, H777, and 316c, using the microdilution checkerboard method of antibiotic and AgNPs mixing. Morphological changes in the bacteria after treatment with the combined antibiotic-AgNPs was observed using scanning electron microscopy (SEM).
Result
The combination of four antibiotics with AgNPs gave fractional inhibitory concentration (FIC) index values and fractional bactericidal concentration (FBC) index values ranging from 0.312 to 0.75 µg/mL and 0.252 to 0.625 µg/mL, respectively, against the three isolates of B. pseudomallei. SEM imaging revealed damage to the bacterial cell structure at the minimal inhibitory concentration (MIC) and FIC levels, while extreme severe cellular damage was observed at the FBC level. Surprisingly, at the FBC level, the bacteria produced large amounts of fibers that are the components of biofilm.
Conclusion
The study clearly shows that most of the combinatorial treatments exhibited synergistic antimicrobial effects against all three isolates of B. pseudomallei. The highest enhancing effect was observed for GENT with AgNPs. We also found that the combination of these antibiotics with AgNPs restored their bactericidal potency in the bacterial strains previously shown to be resistant to the antibiotic. The observed synergistic activities of conventional antibiotics with AgNPs suggest that it might also be possible to achieve equivalent or higher levels of bacterial cell death with lower concentrations of antibiotics using the combined treatments. These results support the use of the antibiotic/AgNPs combination as an alternative design strategy for new therapeutics to more effectively combat melioidosis.
Keywords
Melioidosis, Burkholderia pseudomallei, Silver nanoparticles, Ceftazidime, Synergism, Exopolysaccharide
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This is a preprint. It has not completed peer review.
Research
Combating the melioidosis pathogen using antibiotics in combination with silver nanoparticles
Rina Patramanon
Khon Kaen University Faculty of Science
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9325-2527
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 28 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Melioidosis is an infectious disease caused by the Gram-negative bacillus bacterium, Burkholderia pseudomallei. Due to the emerging resistance of B. pseudomallei to antibiotics, including ceftazidime (CAZ), the development of novel antibiotics and alternative modes of treatment has become an urgent issue. Here, we demonstrate an ability to synergistically increase the efficiency of antibiotics through their combination with silver nanoparticles (AgNPs).
Method:
Combinations of four conventional antibiotics, including CAZ, imipenem (IMI), meropenem (MER), or gentamicin sulfate (GENT), with AgNPs were tested for their bactericidal effects against three isolates of B. pseudomallei, including 1026b, H777, and 316c, using the microdilution checkerboard method of antibiotic and AgNPs mixing. Morphological changes in the bacteria after treatment with the combined antibiotic-AgNPs was observed using scanning electron microscopy (SEM).
Result
The combination of four antibiotics with AgNPs gave fractional inhibitory concentration (FIC) index values and fractional bactericidal concentration (FBC) index values ranging from 0.312 to 0.75 µg/mL and 0.252 to 0.625 µg/mL, respectively, against the three isolates of B. pseudomallei. SEM imaging revealed damage to the bacterial cell structure at the minimal inhibitory concentration (MIC) and FIC levels, while extreme severe cellular damage was observed at the FBC level. Surprisingly, at the FBC level, the bacteria produced large amounts of fibers that are the components of biofilm.
Conclusion
The study clearly shows that most of the combinatorial treatments exhibited synergistic antimicrobial effects against all three isolates of B. pseudomallei. The highest enhancing effect was observed for GENT with AgNPs. We also found that the combination of these antibiotics with AgNPs restored their bactericidal potency in the bacterial strains previously shown to be resistant to the antibiotic. The observed synergistic activities of conventional antibiotics with AgNPs suggest that it might also be possible to achieve equivalent or higher levels of bacterial cell death with lower concentrations of antibiotics using the combined treatments. These results support the use of the antibiotic/AgNPs combination as an alternative design strategy for new therapeutics to more effectively combat melioidosis.
Figure 1
Figure 2
Figure 3