Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, April 2009, p. 1331-1337, Vol. 53, No. 4
0066-4804/09/$08.00+0 doi:10.1128/AAC.01330-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Gallium Maltolate Treatment Eradicates Pseudomonas aeruginosa Infection in Thermally Injured Mice
Katrina DeLeon,1
Fredrik Balldin,1
Chase Watters,1
Abdul Hamood,2
John Griswold,1
Sunil Sreedharan,3 and
Kendra P. Rumbaugh1*
Departments of Surgery,1 Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430,2 Titan Pharmaceuticals, Inc., South San Francisco, California 940803
Received 3 October 2008/ Returned for modification 7 December 2008/ Accepted 24 January 2009
Gallium (Ga) is a semimetallic element that has demonstrated therapeutic and diagnostic-imaging potential in a number of disease settings, including cancer and infectious diseases. Gallium's biological actions stem from its ionic radius being almost the same as that of ferric iron (Fe3+), whereby it can replace iron (Fe) in Fe3+-dependent biological systems, such as bacterial and mammalian Fe transporters and Fe3+-containing enzymes. Unlike Fe3+, ionic gallium (Ga3+) cannot be reduced, and when incorporated, it inactivates Fe3+-dependent reduction and oxidation processes that are necessary for bacterial and mammalian cell proliferation. Most pathogenic bacteria require Fe for growth and function, and the availability of Fe in the host or environment can greatly enhance virulence. We examined whether gallium maltolate (GaM), a novel formulation of Ga, had antibacterial activity in a thermally injured acute infection mouse model. Dose-response studies indicated that a GaM dose as low as 25 mg/kg of body weight delivered subcutaneously was sufficient to provide 100% survival in a lethal P. aeruginosa-infected thermally injured mouse model. Mice treated with 100 mg/kg GaM had undetectable levels of Pseudomonas aeruginosa in their wounds, livers, and spleens, while the wounds of untreated mice were colonized with over 108 P. aeruginosa CFU/g of tissue and their livers and spleens were colonized with over 105 P. aeruginosa CFU/g of tissue. GaM also significantly reduced the colonization of Staphylococcus aureus and Acinetobacter baumannii in the wounds of thermally injured mice. Furthermore, GaM was also therapeutically effective in preventing preestablished P. aeruginosa infections at the site of the injury from spreading systemically. Taken together, our data suggest that GaM is potentially a novel antibacterial agent for the prevention and treatment of wound infections following thermal injury.
* Corresponding author. Mailing address: Texas Tech University Health Sciences Center, Department of Surgery, 3601 4th Street, Lubbock, TX 79430. Phone: (806) 743-2460, ext. 264. Fax: (806) 743-2370. E-mail: kendra.rumbaugh{at}ttuhsc.edu
Published ahead of print on 2 February 2009.
Antimicrobial Agents and Chemotherapy, April 2009, p. 1331-1337, Vol. 53, No. 4
0066-4804/09/$08.00+0 doi:10.1128/AAC.01330-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»