Alternative therapy against CTX-M broad spectrum β-lactamase resistance gene in Klebsiella pneumoniae infection: bee venom and bee venom-derived nanovesicle fraction.

Antibiotic resistance is one of the most important problems threatening global public health by complicating the treatment of infections worldwide. The increase in resistant microorganisms creates a serious economic and social burden on healthcare systems and increasingly limits treatment options. Conscious use of antibiotics, infection control measures and the development of alternative treatment strategies are vital to ensure sustainability in health. Klebsiella pneumoniae is the most common gram-negative bacterium among urinary tract infections. Treatment of infections has become difficult due to the resistance to beta-lactam antibiotics. Bee venom (BV) and nanovesicle fractions isolated from BV are bioactive compounds with antimicrobial and antibiofilm activity. The aim of this study was to determine the antimicrobial and antibiofilm effects of BVand bee venom-derived nanovesicle fractions against the nosocomial infection agent K. pneumoniae, and to evaluate CTX-M PCR band detection under the tested conditions. Minimum inhibitory concentration (MIC), antibiofilm activity, fractional inhibition concentrations (FIC), CTX-M PCR band detection, and viability rates in L929 cells were evaluated for both BVand the bee venom-derived nanovesicle fraction against K. pneumoniae. MIC value of nanovesicle fractions isolated from BVwas determined as 1.95 mg/L. In combination with piperacillin and tazobactam, a synergistic effect was detected with a value of 0.5. Antibiofilm activity was measured with the highest absorbance value of 0.163 and 0.094 for BV nanovesicle fractions. A detectable CTX-M PCR band was observed in the BVgroup at 0.5× MIC, whereas no detectable band was observed at both concentrations by day 4. In the bee venom-derived nanovesicle fraction group, no detectable CTX-M PCR band was observed at 2× MIC and 0.5× MIC under the tested conditions. In contrast, detectable CTX-M PCR bands were observed in the piperacillin-tazobactam group. It was reported that the combination groups decreased the viability rate in L929 cell lines. The bee venom-derived nanovesicle fraction showed antimicrobial, antibiofilm, and PCR-based detection findings under the tested conditions, supporting the need for further investigation in broader in vitro and in vivo models.