Mode of action of novel polyamines increasing the permeability of bacterial outer membrane

Polyamines Increase Antibiotic Susceptibility in Pseudomonas aeruginosa

“…Polyamines are also involved in control of membrane permeability by blocking outer membrane porin channels (e.g., OmpF and OmpC) in E. coli (3). In contrast, the synthetic polyamine analogues naphthylacetylspermine and methoctramine were reported to increase the outer membrane permeability by disruption of LPS integrity, resulting in increased susceptibility of E. coli to hydrophobic antibiotics (32). An early study conducted by Vaara and Vaara concluded that cadaverine, spermidine, and spermine at submillimolar concentrations had neither bactericidal nor sensitizing activity to antibiotics in E. coli (28).…”

In situ potentiometric method to evaluate bacterial outer membrane-permeabilizing ability of drugs: Example using antiprotozoal diamidines

“…This barrier is formed through cross-bridging between lipopolysaccharide molecules via divalent cations (Ca 2+ and Mg 2+ ). Thus, metal ion chelators, such as EDTA, certain cationic peptides, and polyamines, which can attack the binding sites of divalent cations, are able to disrupt the organization of the outer membrane, increasing its permeability, and therefore sensitize bacteria to hydrophobic antibiotics that otherwise ineffectively traverse the outer membrane (Salmi and Brunel, 2007;Savage et al, 2002;Vaara, 1992;Yasuda et al, 2004). A structural requirement of agents to increase the permeability of the outer membrane at relatively low concentrations is the presence of at least two positively charged groups with an amphiphilic moiety (Katsu, 1991;Katsu et al, 1985).…”

“…Although aromatic diamidines, such as diminazene, pentamidine, and DAPI, have been known to possess antibacterial activity (Anné et al, 1980), their outer membranepermeabilizing ability has not yet been investigated. We first examined such ability with a standard microbiological assay (Yasuda et al, 2004;Urakawa et al, 2010), using the synergistic effect of diamidine and an antibiotic that ineffectively traverse the outer membrane of Gramnegative bacteria. We applied novobiocin and tyrocidine A as antibiotics.…”

“…We applied novobiocin and tyrocidine A as antibiotics. Although novobiocin is widely used for this purpose (Yasuda et al, 2004;Urakawa et al, 2010), we introduced tyrocidine A to obtain further evidence for outer membrane permeabilization. Because tyrocidine A can increase the permeability of the phospholipid layers constituting the cytoplasmic membrane of living cells (Aranda and De Kruijff, 1988), its use in combination with an outer membrane permeabilizer induced the leakage of K + present in the cytoplasm of bacteria.…”

Antimicrobial Activities of 3-Amino- and Polyaminosterol Analogues of Squalamine and Trodusquemine

“…Recently, Katsu et al examined the structure-activity relationship between functionalized polyamines and the outer membranes of Gramnegative bacteria and demonstrated that lipophilic moieties and a number of amino groups in polyamines were important for permeabilisation of such an outer membrane. [18] In the same context, various polyamine conjugated to cholesterol, cholenic acid and bile acids have been reported possessing significant antimicrobial activities and reduced hemolytic potentials. [19 -23] Nevertheless, all these synthesis were performed in numerous steps and low overall chemical yields.…”