Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens

Abstract

Multidrug-resistance due to "β lactamases having the expanded spectrum" (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX-M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug-resistance in ESBL producing strains. Here, two CTX-M-15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of "cefotaxime loaded gold-nanoparticles." Bromelain was used for both reduction and capping in the process of synthesis of gold-nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV-Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth-dilution method for the estimation of the antibacterial-activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802-2808, 2017. © 2017 Wiley Periodicals, Inc.

Formulation of Ceftriaxone Conjugated Gold Nanoparticles and Their Medical Applications against Extended-Spectrum β -Lactamase Producing Bacteria and Breast Cancer

“…2A and 2B) and the size of the AuNP and Cef-AuNP were determined to be at 14.2-25.3 nm and 26.6-45.8 nm, respectively. These results suggested that there was an increase in the size of the AuNP due to the attachment of ceftriaxone to the AuNP and these results agree with Shaikh et al [32]. TEM analysis showed that all these AuNP were of spherical, hexagonal, and triangular shape.…”

Nano-Strategies to Fight Multidrug Resistant Bacteria—“A Battle of the Titans”

“…The authors could invert resistance in cefotaxime resistant bacterial strains (i.e., E. coli and K. pneumoniae ) by using cefotaxime-AuNPs. Their results reinforce the efficacy of conjugating an unresponsive antibiotic with AuNPs to restore its efficacy against otherwise resistant bacterial pathogens (Shaikh et al, 2017 ).…”

Mechanistic Insights into the Antimicrobial Actions of Metallic Nanoparticles and Their Implications for Multidrug Resistance

“…Shaikh and co-workers observed a similar mechanism for cefotaxime-capped AuNPs against drug-resistant microbial pathogens that generate extended spectrum beta-lactamase (antibiotic-degrading enzymes) [45]. It was postulated high cefotaxime concentrations were deposited in bacterial cells by AuNPs and that this might inhibit the cell wall before being degraded by bacterial beta lactamase enzyme.…”