Antimicrobial activity of gallium protoporphyrin IX against Acinetobacter baumannii strains displaying different antibiotic resistance phenotypes

Brock A. Arivett, Steven E. Fiester, Emily J. Ohneck, William F. Penwell, Cynthia M. Kaufman, Ryan Relich, Luis A. Actis

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606T and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606T and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606T or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.

Original languageEnglish (US)
Pages (from-to)7657-7665
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number12
DOIs
StatePublished - Dec 1 2015

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Acinetobacter baumannii
Gallium
Microbial Drug Resistance
Phenotype
Acinetobacter Infections
Anti-Bacterial Agents
Larva
Iron
Microbial Viability
Therapeutics
Infection
protoporphyrin IX
Cations
Clone Cells
Bacteria
Survival
Growth

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Antimicrobial activity of gallium protoporphyrin IX against Acinetobacter baumannii strains displaying different antibiotic resistance phenotypes. / Arivett, Brock A.; Fiester, Steven E.; Ohneck, Emily J.; Penwell, William F.; Kaufman, Cynthia M.; Relich, Ryan; Actis, Luis A.

In: Antimicrobial Agents and Chemotherapy, Vol. 59, No. 12, 01.12.2015, p. 7657-7665.

Research output: Contribution to journalArticle

Arivett, Brock A. ; Fiester, Steven E. ; Ohneck, Emily J. ; Penwell, William F. ; Kaufman, Cynthia M. ; Relich, Ryan ; Actis, Luis A. / Antimicrobial activity of gallium protoporphyrin IX against Acinetobacter baumannii strains displaying different antibiotic resistance phenotypes. In: Antimicrobial Agents and Chemotherapy. 2015 ; Vol. 59, No. 12. pp. 7657-7665.
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