title: Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates.
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.
authors.affiliation: Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Ft. Sam Houston, San Antonio, TX 78234, USA. david.chang6.mil@mail.mil.
authors.forename: David
authors.initials: D
authors.lastname: Chang
authors.affiliation: United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Ft. Sam Houston, San Antonio, TX 78234, USA. rebecca.a.garcia28.ctr@mail.mil.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Garcia
authors.affiliation: Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Ft. Sam Houston, San Antonio, TX 78234, USA. kevin.s.akers.mil@mail.mil.|United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Ft. Sam Houston, San Antonio, TX 78234, USA. kevin.s.akers.mil@mail.mil.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
authors.affiliation: Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Ft. Sam Houston, San Antonio, TX 78234, USA. katrin.mende.ctr@mail.mil.|Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. katrin.mende.ctr@mail.mil.
authors.forename: Katrin
authors.initials: K
authors.lastname: Mende
authors.affiliation: Infectious Disease Service, Department of Medicine, San Antonio Military Medical Center, Ft. Sam Houston, San Antonio, TX 78234, USA. clinton.k.murray.mil@mail.mil.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
authors.affiliation: United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Ft. Sam Houston, San Antonio, TX 78234, USA. joseph.c.wenke.civ@mail.mil.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine, Ft. Sam Houston, San Antonio, TX 78234, USA. sanchezcj@livemail.uthscsa.edu.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Sanchez
keywords: Acinetobacter baumannii; biofilm; gallium mesoporphyrin IX; gallium protoporphyrin IX; multidrug-resistant