Silver Nanoparticles Enhance Antimicrobial Efficacy of Antibiotics and Restore That Efficacy against the Melioidosis Pathogen

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.

Characterization and Rate of Killing of Conjugated Silver Nanoparticles Against Selected Clinical Bacterial Isolates

“…The maximum wavelength obtained (410.33 nm) when ultraviolet-visible spectroscopy of conjugated silver nanoparticles was determined in line with the studies carried out by Kasthuri et al (2009); Malawong et al (2021), which obtained similar results (Table 2). The size distribution of CAgNPs revealed an average size of 237.8 d.nm and was confirmed by the TEM image shown in Figure 3.…”

A Critical Review of the Antimicrobial and Antibiofilm Activities of Green-Synthesized Plant-Based Metallic Nanoparticles

“…This may subsequently alter cell surface permeability, leading to the death of bacteria and fungi [ 399 ]. In addition, aminoglycoside antibiotics (e.g., gentamicin, neomycin, paromomycin) that are positively charged at physiological pH can synergize with all kinds of MNPs [ 400 , 401 ]. On the other hand, depending on their zeta potential, phytocomponents that act as stabilizing and capping agents can reduce the propensity of biosynthesized nanoparticles to aggregate, which influences their size, shape, stability and biological activity [ 392 , 402 ].…”

Green Extracellular Synthesis of Silver Nanoparticles by Pseudomonas alloputida, Their Growth and Biofilm-Formation Inhibitory Activities and Synergic Behavior with Three Classical Antibiotics

“…The combined use of AgNPs and classic antibiotics may help to decrease the concentrations needed and perhaps the cytotoxic effects, as shown in [ 78 ]. This can also be useful for the recovering of antibiotics not used because of high levels of pathogen resistance, toxic effects on bacterial hosts, and perhaps the impossibility of reaching sufficient concentrations in the host’s fluids or tissues for effective activity [ 39 , 41 , 42 , 79 ]. Mechanisms involved in AgNPs–antibiotic synergy have not been extensively studied, but some authors have correlated this phenomenon with the existence of an interaction between both components, which generates complexes that interact better with the bacterial envelopes and produce a higher release of Ag + from the AgNPs [ 80 ], but the possibility of other mechanisms involving the proprietary mechanisms of each of the agents should not be ignored.…”

“…This would allow us, if synergy occurs, to use lower concentrations of antibiotics and AgNPs than when they are used alone [ 39 , 40 ]. Moreover, recent studies have shown that AgNPs can be used to recover the use of certain classical antibiotics not regularly used because of their toxic effects or resistance [ 41 , 42 ].…”