Polyamines Increase Antibiotic Susceptibility in Pseudomonas aeruginosa
Year: 2006
Type: article
Abstract: Pseudomonas aeruginosa is an opportunistic human pathogen. Treatment is complicated by frequent acquired resistance to antipseudomonal therapies. Polyamines (cadaverine, putrescine, spermidine, and spermine) are ubiquitous polycationic compounds essential for all living organisms. In a dose-dependent manner, polyamines increased the susceptibility of P. aeruginosa to 14 beta-lactam antibiotics, chloramphenicol, nalidixic acid, and trimethoprim as demonstrated by a reduction in MIC of up to 64-fold. This effect was partially antagonized (25 to 50%) by the presence of 10 mM of Mg(2+) or Ca(2+). In contrast, the effects of the outer membrane permeabilizers, polymyxin B nonapeptide and EDTA, were completely abolished by 3 mM Mg(2+) or Ca(2+). Changes on the outer membrane barrier by these compounds were assessed by activity measurements of periplasmic beta-lactamase. The results showed that while EDTA and polymyxin B serve as outer membrane disorganizing agents as expected, exogenous spermidine and spermine did not exhibit any apparent effect on outer membrane permeability or rupture. In summary, these results strongly suggest that the increased antibiotic susceptibility by polyamines is exerted by a mechanism that differs from that of EDTA and polymyxin B. Polyamines might be potentially useful in antipseudomonal therapies by increasing the effectiveness of certain beta-lactam antibiotics.
Authors: Dong H. Kwon, Chung-Dar Lu
Institution: Georgia State University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Science Foundation
OpenAlex ID: W2143678351