Potential Novel Therapeutic Strategies in Cystic Fibrosis: Antimicrobial and Anti-Biofilm Activity of Natural and Designed α-Helical Peptides Against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia

Abstract

Background: Secondary metabolites ranging from furanone to exo-polysaccharides have been suggested to have anti-biofilm activity in various recent studies. Among these, Escherichia coli group II capsular polysaccharides were shown to inhibit biofilm formation of a wide range of organisms and more recently marine Vibrio sp. were found to secrete complex exopolysaccharides having the potential for broad-spectrum biofilm inhibition and disruption.

Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species ofPaenibacillus

“…Based on the findings, the first compound reported here as an amino acid antibiotic with the name Leucine 2-(hydroxymethoxyphosphinyl)-2-methylhydrazide has a phosphate group in it and, thus, it can be proposed that its electronegative property might modulate the surface of the tested organism in such a way that there is an inhibition of the cell-surface attachment. This was similar to a previous study where it was reported that the identified polysaccharide compounds might interfere with the cell-surface influencing cell-cell interactions of a wide range of bacterial isolates [13]. The second compound reported here as a phospholipase A2 inhibitor with the name 4-Hydroxy-5-(hydroxymethyl)-3-(14-methylpentadecanoyl) tetronicacid-2(5H)-furanone has a similar chemical structure to the previously identified quorum-sensing antagonist (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone from the marine alga Delisea pulchra which was reported to inhibit the biofilm formation in E. coli without inhibiting its growth [34].…”

“…It is worth mentioning that the administration of antimicrobial agents and biocide compounds in the local sites of some infection has been a useful approach to combat microbial biofilms [12]. However, prolonged persistence of these compounds in the environment could induce toxicity towards nontarget organisms and resistance among microorganisms within biofilms [13]. Moreover, some of these compounds may exhibit toxic effects even at therapeutic doses which makes it necessary to test their toxicity in experimental animals [14].…”

Role of capsular polysaccharide (CPS) in biofilm formation and regulation of CPS production by quorum‐sensing in Vibrio vulnificus

“…In addition, it is also possible for the hydrophilic CPS may mask hydrophobic structures on the bacterial surface, such as pili (Joseph and Wright, 2004). Extracellular polysaccharides have been reported to inhibit biofilm formation in other bacteria, such as group II CPS of Escherichia coli, a polysaccharide of Vibrio sp., and an exopolysaccharide from Bacillus licheniformis (Valle et al, 2006;Jiang et al, 2011;Sayem et al, 2011).…”

Antibiofilm polysaccharides

“…Studies utilizing culture supernatants or purified antibiofilm polysaccharides as surface coatings have provided further evidence that antibiofilm polysaccharides modify the physical properties of abiotic surfaces. Precoating microtiter plate wells with B. licheniformis SP1 culture supernatants, for example, inhibited biofilm formation by E. coli (Sayem et al, 2011). Similarly, pretreatment of glass surfaces with E. coli K2 supernatants reduced biofilm formation by E. coli, S. aureus, S. epidermidis, E. faecalis, K. pneumoniae and P. aeruginosa in microfermentors (Valle et al, 2006), and pretreatment of glass slides with purified E. coli Ec300p inhibited S. aureus biofilm formation in a flow reactor (Rendueles et al, 2011).…”

“…Sayem and colleagues (2011) screened cell-free culture supernatants from 10 different bacteria associated with the marine sponge Spongia officinalis and found that two supernatants significantly inhibited E. coli biofilm formation in a microtiter plate assay. One of the active supernatants (designated SP1) was from a bacterium identified as Bacillus licheniformis (Sayem et al, 2011). In addition to inhibiting E. coli biofilm formation, SP1 supernatant also inhibited biofilm formation by Acinetobacter sp., S. aureus, Salmonella typhimurium, Shigella sonnei, Listeria monocytogenes, Bacillus cereus, Bacillus amyloliquefaciens, Bacillus pumilus and Bacillus subtilis without inhibiting growth.…”