<p>Synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant <em>Acinetobacter baumannii</em> and <em>Klebsiella pneumoniae</em></p>

Abstract

Purpose The activity of the cationic antimicrobial peptide WLBU2 was evaluated against planktonic cells and biofilms of multi-drug resistant (MDR) Acinetobacter baumannii and Klebsiella pneumoniae , alone and in combination with classical antimicrobial agents. Methods Control American Type Culture Collection (ATCC) strains and MDR clinical isolates of A. baumannii and K. pneumoniae were utilized. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of WLBU2 alone and in combination with antimicrobials were determined by classical methods. The Calgary biofilm device was used to determine the minimum biofilm eradication concentration (MBEC). The MTT assay was used to determine the cytotoxicity of agents on eukaryotic cells. The electrophoretic mobility shift assay was used to evaluate the ability of WLBU2 to bind bacterial DNA. Results The WLBU2 MIC and MBC values were identical indicating bactericidal activity. The MIC/MBC values ranged from 1.5625 to 12.5 µM. At these concentrations, Vero cells and human skin fibroblasts were viable. The MBEC of WLBU2 ranged from 25 to 200 µM. A significant loss of eukaryotic cell viability was observed at the MBEC range. The combination of sub-inhibitory concentrations of WLBU2 with amoxicillin-clavulanate or ciprofloxacin for K. pneumoniae , and with tobramycin or imipenem for A. baumannii , demonstrated synergism, leading to a significant decrease in MIC and MBEC values for some isolates and ATCC strains. However, all combinations were associated with considerable loss in eukaryotic cells’ viability. WLBU2 did not demonstrate the ability to bind bacterial plasmid DNA. Conclusion WLBU2 in combination with antimicrobials holds promise in eradication of MDR pathogens.

Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers

“…The remaining compounds were less effective or even inactive. A. baumannii and K. pneumoniae were classified by Swedan et al as strong biofilm producers, this offering an explanation of their relatively low susceptibility [ 110 ]. Persister cells are believed to be one of the factors that can contribute to high biofilm resistance to antibiotics.…”

Antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles fabricated fromMespilus germanicaextract against multidrug resistance ofKlebsiella pneumoniaeclinical strains

“…K. pneumoniae is a major nosocomial infection, found worldwide, that shows resistance to many commonly used antibiotics and has the ability to form biofilms on different physiological surfaces and medical devices [27][28][29][30][31]. Hence, there is a need for inhibition of the bacterial biofilm formation to control the infection, while, biologically synthesized NPs are new agents with antibiofilm activity [32].…”

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

“…For instance, the MIC does not allow a differentiation between the bacteriostatic and bactericidal activities of an HDP. Furthermore, an HDP may be bactericidal and eradicate biofilms (Dall et al, 2018;Swedan et al, 2019). Bacteriostatic antibiotics act by fully or partially inhibiting bacterial growth (Wiegand et al, 2008); however, growth will resume after removal of the antibiotic.…”