Abstract
Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics. Silver nanoparticles (AgNPs) are an interesting agent to develop to solve this bacterial resistance. Here, we characterize and assess the antimelioidosis activity of AgNPs against these pathogenic bacteria. AgNPs were characterized and displayed a maximum absorption band at 420 nm with a spherical shape, being well-monodispersed and having high stability in solution. The average size of AgNPs is 7.99 ± 1.46 nm. The antibacterial efficacy of AgNPs was evaluated by broth microdilution. The bactericidal effect of AgNPs was further assessed by time-kill kinetics assay. Moreover, the effect of AgNPs on the inhibition of the established biofilm was investigated by the crystal violet method. In parallel, a study of the resistance induction development of B. pseudomallei towards AgNPs with efflux pump inhibiting effect was performed. We first found that AgNPs had strong antibacterial activity against both susceptible and ceftazidime-resistant (CAZ-resistant) strains, as well as being efficiently active against B. pseudomallei CAZ-resistant strains with a fast-killing mode via a bactericidal effect within 30 min. These AgNPs did not only kill planktonic bacteria in broth conditions, but also in established biofilm. Our findings first documented that the resistance development was not induced in B. pseudomallei toward AgNPs in the 30th passage. We found that AgNPs still showed an effective efflux pump inhibiting effect against these bacteria after prolonged exposure to AgNPs at sublethal concentrations. Thus, AgNPs have valuable properties for being a potent antimicrobial agent to solve the antibiotic resistance problem in pathogens.
Highlights
Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics, leading to the need for alternative agents for the treatment of melioidosis [1]
The results show that LL-37 and LL-31 exhibited a rapid bactericidal effect against E. coli within 30 min, whereas AgNPs and ceftazidime could kill E. coli within 1 h (Figure 4a)
To determine these time-kill kinetics assay against B. pseudomallei, the results showed that AgNPs could kill B. pseudomallei strongly within 30 min, whereas ceftazidime could slowly kill this pathogenic bacterium within 24 h
Summary
Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics, leading to the need for alternative agents for the treatment of melioidosis [1]. B. pseudomallei has recently developed resistance to several groups of antibiotics, including aminoglycosides, macrolides, quinolones, penicillin, rifamycin, as well as first, second, and third generations of cephalosporins [2] To overcome this problem, many studies have demonstrated the better antibacterial effects of alternative agents. Many studies have reported that B. pseudomallei becomes resistant to CAZ [6] This occurrence decreases the efficacy of CAZ treatment and increases relapses in melioidosis patients. Tannic acid stabilized-silver nanoparticles present effective antimicrobial activity against various bacteria, including antibiotic-resistant strains. Phytochemical tannic acid has been evaluated from previous work to act as an effective efflux pump inhibitor (EPI) in preventing bacterial resistance induction in prolonged exposure to a sublethal dose of the antibacterial agent [19,20]. The investigation of resistance induction of this bacteria after prolonged exposure to sublethal concentrations of AgNPs, as well as prolonged activity of efflux pump inhibiting efficacy were performed
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