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Pharmaceuticals 2016, 9(1), 16; doi:10.3390/ph9010016

Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

1
Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Ft. Sam Houston, San Antonio, TX 78234, USA
2
United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Ft. Sam Houston, San Antonio, TX 78234, USA
3
Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dacheng Ren
Received: 5 January 2016 / Revised: 12 March 2016 / Accepted: 15 March 2016 / Published: 17 March 2016
(This article belongs to the Special Issue Microbial Biofilms)
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Abstract

Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. View Full-Text
Keywords: Acinetobacter baumannii; biofilm; multidrug-resistant; gallium mesoporphyrin IX; gallium protoporphyrin IX Acinetobacter baumannii; biofilm; multidrug-resistant; gallium mesoporphyrin IX; gallium protoporphyrin IX
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MDPI and ACS Style

Chang, D.; Garcia, R.A.; Akers, K.S.; Mende, K.; Murray, C.K.; Wenke, J.C.; Sanchez, C.J. Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates. Pharmaceuticals 2016, 9, 16.

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