Abstract
Melioidosis is an infectious disease caused by Gram-negative bacillus bacteria 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 demonstrated an ability to synergistically increase the efficiency of antibiotics through their combination with silver nanoparticles (AgNPs). Combinations of four conventional antibiotics including CAZ, imipenem (IMI), meropenem (MER), and gentamicin sulfate (GENT) with starch-stabilized AgNPs were tested for their antibacterial effects against three isolates of B. pseudomallei. The combination of each antibiotic with AgNPs featured 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. The study clearly showed 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. These results confirmed the combination of each antibiotic with AgNPs restored their bactericidal potency in the bacterial strains that had previously been shown to be resistant to the antibiotics. In addition, morphological changes examined by SEM confirmed that the bacterial cells were severely damaged by combinations at the FBC level. Although bacteria produce fibers to protect themselves, ultimately the bacteria were killed by the antibiotic-AgNPs combinations. Overall, these results suggest the study of antibiotic-AgNPs combinations as an alternative design strategy for potential therapeutics to more effectively combat the melioidosis pathogen.