Antibacterial and antibiofilm efficacy of synthetic polymyxin‐mimetic lipopeptides

Abstract

The increasing emergence of multidrug‐resistant bacteria is a huge problem to society providing significant risks to public health. This has been further escalated by a decline in the clinical translation of new antibacterial drug classes since the 1980s. In this article, we describe the synthesis, antibacterial/antibiofilm activity and in vitro toxicity of synthetic low molecular weight lipopeptides mimetics of polymyxin. C12‐KTKCKFLKKC‐NH2 and C14‐KTKCKFLKKC‐NH2 lipopeptides demonstrated activity against both planktonic and biofilm forms of Staphylococcus epidermidis, Staphylococcus aureus, MRSA, Escherichia coli, and Acinetobacter baumannii. Peptide‐outer membrane interaction was studied using lipopolysaccharide neutralization and N‐phenyl‐1‐napthylamine assays. C12‐conjugated peptide significantly neutralized lipopolysaccharide at concentrations lower than minimum inhibitory concentration values against Gram‐negative E coli, by an average of 90% and demonstrated up to double the outer membrane permeabilization ability of 10 mg/mL polymyxin B. Polymyxin‐mimetic lipopeptides have the potential to undergo further in vitro and in vivo study to enable clinical translation and help alleviate the current antimicrobial crisis.

Comparative <i>in vitro</i> activity of various antibiotic against planktonic and biofilm and the gene expression profile in <i>Pseudomonas aeruginosa</i>

“…A biofilm is an aggregation of one or more species of microorganisms adhered to a surface, as compared to planktonic bacteria, which exist as individual organisms [20] , [51] . Biofilm-forming bacteria are reported to be 100–1000 times more resistant to antibiotics than planktonic bacteria [13] , [14] . In this study, biofilm inhibition and reduction-crystal violet assay suggested that all the tested antibiotics at 8, 4, 2, 1 and 0.5 µg/mL concentrations were significantly able to decrease P. aeruginosa biofilm formation.…”

“…Resistance to antibiotics is approximately 1000 fold more in attached bacteria than planktonic cells because of an increase in mutation rates, upregulation of efflux pumps, decrease in metabolic activity, and other physical reasons [13] . The resistance mechanism is unique to biofilm-encapsulated bacteria as the biofilm phenotype provides a protective advantage [13] , [14] . Bacteria alter gene expression during biofilm development adaption, encouraging phenotypically different behavior compared to planktonic counterparts.…”

Comparison of the antimicrobial and antivirulence activities of Sidr and Tualang honeys with Manuka honey against Staphylococcus aureus

“…The percentage of biofilm inhibition was estimated using the formulas shown below. The experiment was carried out in triplicate ( 18 , 19 , 22 , 23 ). …”

Assessment of persistent antimicrobial and anti-biofilm activity of p-HEMA hydrogel loaded with rifampicin and cefixime

“…The adhesion of bacteria on the catheter surface is governed by reversible weak forces such as Van der Waals or electrostatic attraction forces and then by the formation of irreversible strong forces like covalent bonds 6 . Bacteria attached to the biomaterial surface leads to subsequent colonization and eventually provoke the formation of biofilms 7 – 9 as illustrated in Fig. 1 .…”