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Antimicrobial Agents and Chemotherapy, May 2006, p. 1623-1627, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1623-1627.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Polyamines Increase Antibiotic Susceptibility in Pseudomonas aeruginosa

Dong H. Kwon and Chung-Dar Lu*

Department of Biology, Georgia State University, Atlanta, Georgia 30303

Received 14 June 2005/ Returned for modification 27 July 2005/ Accepted 1 February 2006

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 ß-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 Mg2+ or Ca2+. In contrast, the effects of the outer membrane permeabilizers, polymyxin B nonapeptide and EDTA, were completely abolished by 3 mM Mg2+ or Ca2+. Changes on the outer membrane barrier by these compounds were assessed by activity measurements of periplasmic ß-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 ß-lactam antibiotics.

* Corresponding author. Mailing address: Department of Biology, Georgia State University, 24 Peachtree Center Avenue, Atlanta, GA 30303. Phone: (404) 651-2531. Fax: (404) 651-2509. E-mail: biocdl{at}langate.gsu.edu.

Antimicrobial Agents and Chemotherapy, May 2006, p. 1623-1627, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1623-1627.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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