Antibiofilm effect of melittin alone and in combination with conventional antibiotics toward strong biofilm of MDR-MRSA and -Pseudomonas aeruginosa

Abstract

IntroductionMultidrug-resistant (MDR) pathogens are being recognized as a critical threat to human health if they can form biofilm and, in this sense, biofilm-forming MDR-methicillin resistant Staphylococcus aureus (MRSA) and -Pseudomonas aeruginosa strains are a worse concern. Hence, a growing body of documents has introduced antimicrobial peptides (AMPs) as a substitute candidate for conventional antimicrobial agents against drug-resistant and biofilm-associated infections. We evaluated melittin’s antibacterial and antibiofilm activity alone and/or in combination with gentamicin, ciprofloxacin, rifampin, and vancomycin on biofilm-forming MDR-P. aeruginosa and MDR-MRSA strains.MethodsMIC, MBC, MBIC, and MBEC indices for melittin were in the range of 0.625–5, 1.25–10, 2.5–20, and 10–40 μg/ml, respectively. The findings found that the combination of melittin AMP with antibiotics was synergistic and fractional biofilm inhibitory concentration index (FBICi) for most tested concentrations was <0.5, resulting in a significant reduction in melittin, gentamicin, ciprofloxacin, vancomycin, and rifampin concentrations by 2–256.4, 2–128, 2–16, 4–64 and 4–8 folds, respectively. This phenomenon reduced the toxicity of melittin, whereby its synergist concentration required for biofilm inhibition did not show cytotoxicity and hemolytic activity. Our findings found that melittin decreased the expression of icaA in S. aureus and LasR in P. aeruginosa genes from 0.1 to 4.11 fold for icaA, and 0.11 to 3.7 fold for LasR, respectively.ResultsThe results showed that: (1) the quality of personal relationships significantly and positively correlated with academic performance; (2) Among the three types of relationships tested, the quality of student-peer relationships was the most closely associated with academic achievement.DiscussionOverall, the results obtained from our study show that melittin alone is effective against the strong biofilm of MDR pathogens and also offers sound synergistic effects with antibiotics without toxicity. Hence, combining melittin and antibiotics can be a potential candidate for further evaluation of in vivo infections by MDR pathogens.

Acinetobacter baumannii biofilm was inhibited by tryptanthrin through disrupting its different stages and genes expression

“…The criteria for determining the biofilm formation ability of strains are listed in the table below. 54 A. baumannii strains with strong biofilm formation ability were used to detect the antibiofilm ability of tryptanthrin.…”

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities

“…The antibacterial activity of melittin was determined by measuring their MIC using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guidelines [41,42]. For MIC, a broth dilution susceptibility test was performed using Mueller-Hinton broth (MHB) [33,43,44]. Fresh bacterial colonies were incubated in MHB at 37 • C and 200 rpm overnight, a bacterial suspension with optical density (OD 600 ) between 0.9 and 1 is equal to 10 9 colony forming units (CFU)/mL, and the bacterial suspension was diluted with MHB broth to 10 6 CFU/mL.…”

New Strategies to Kill Metabolically-Dormant Cells Directly Bypassing the Need for Active Cellular Processes

“…Applying AMPs with conventional antibiotics or using AMPs cocktails are also promising anti-biofilm and anti-persister strategies [ 206 ]. For example, melittin, the main component of bee venom, in combination with a broad spectrum of antibiotics (e.g., gentamicin, ciprofloxacin, vancomycin, and rifampin), is strongly effective against biofilm-forming MDR-MRSA and MDR- P. aeruginosa [ 207 ]. Rishi et al have demonstrated that the nisin–ampicillin combination (0.5 μg/mL and 100 μg/mL, respectively) in the presence of mannitol (25 mM) eliminated Salmonella persister cells [ 208 ].…”