Antimicrobial Peptides against Multidrug-Resistant Pseudomonas aeruginosa Biofilm from Cystic Fibrosis Patients

Abstract

Lung infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by Pseudomonas aeruginosa . Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like P. aeruginosa . Antimicrobial peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity. Here we investigated a series of AMPs ( d , l -K 6 L 9 ), each composed of six lysines and nine leucines but differing in their sequence composed of l - and d -amino acids. The d , l -K 6 L 9 peptides showed antimicrobial and antibiofilm activities against P. aeruginosa from CF patients. Furthermore, the data revealed that the d , l -K 6 L 9 peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d , l -K 6 L 9 peptides do not induce bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant bacterial biofilms.

An intrinsically disordered antimicrobial peptide dendrimer from stereorandomized virtual screening

“…The approach might be further applicable to optimize the sequence of intrinsically disordered linear peptides, for example the AMP indolicidin, 60 , 61 , 62 , 63 or Leu-Lys oligomers known to tolerate mixed chirality arrangements for membrane disruption. 13 , 64 , 65 , 66 The discovery of homochiral, intrinsically disordered AMPDs such as L- and D- X22 matching the high activity and low toxicity of the parent sr -AMPD overcomes the intrinsic difficulty of characterizing the billions of stereoisomers composing sr -sequences (68,719,476,736 in the case of sr - X22 ) and therefore opens the way for further development of these compounds.…”

Targeting Multidrug-Recalcitrant Pseudomonas aeruginosa Biofilms: Combined-Enzyme Treatment Enhances Antibiotic Efficacy

“… Pseudomonas aeruginosa is an increasingly prevalent opportunistic human pathogen causing a wide range of acute and chronic infections in patients with severe burns, metabolic diseases, and cystic fibrosis. The P. aeruginosa biofilm has strong resistance to antibiotics ( 1 , 2 ). Along with biofilm formation, the mortality from P. aeruginosa infection increases with the production of various virulence factors such as lectin, exotoxin A, pyocyanin, elastase, and alginate, which assist P. aeruginosa in evading the host’s immune response and causing pathological damage ( 3 , 4 ).…”

Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

“…β-defensin analogues were developed with enhanced antimicrobial activity against P. aeruginosa , even with elevated salt concentrations, which is a relevant feature in CF patients [ 44 , 45 ]. The synthetic peptide D,L -K 6 L 9 has shown potent antimicrobial and anti-biofilm activity against P. aeruginosa and high stability to degradation by sputum proteases [ 46 ]. Unfortunately, despite their strong effectiveness and potent broad-spectrum activity, the clinical applications of AMPs are limited due to their poor proteolytic stability [ 47 , 48 ].…”