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<p>The increased incidence of multi-drug resistant (MDR) <i>Proteus mirabilis</i> highlights the need for novel antibiotics targeting <i>P. mirabilis</i>. In this study, we examined the potential antibacterial effects of gallium-based antimicrobials on <i>P. mirabilis</i>. We performed in vitro susceptibility testing of gallium compounds against <i>P. mirabilis</i> UTI isolates. Ga(NO<sub>3</sub>)<sub>3</sub> and gallium protoporphyrin IX (GaPP) effectively inhibited <i>P. mirabilis</i> growth, with minimum inhibitory concentrations (MIC) of 64 μg/ml and 2.5 μg/ml, respectively. To further assess the effects of gallium compounds on <i>P. mirabilis</i> growth we performed time-kill assays. Ga(NO<sub>3</sub>)<sub>3</sub> was bacteriostatic and prevented <i>P. mirabilis</i> growth over time, while GaPP was bactericidal, effectively killing <i>P. mirablis</i> over time. Free iron in the form of ferric ammonium citrate (FAC) reversed the inhibitory effects of Ga(NO<sub>3</sub>)<sub>3</sub>, while the addition of hemin reversed the effects of GaPP on <i>P. mirabilis</i> growth. In vivo, GaPP administered intravesically to the bladder reduced bacterial burden in an animal model of <i>P. mirabilis</i> urinary tract infection. Our results demonstrate that Ga(NO<sub>3</sub>)<sub>3</sub> and GaPP disrupt free iron/heme and siderophore-based iron acquisition in <i>P. mirabilis</i> to inhibit growth. Further work is needed to better determine the effectiveness of gallium in vivo and the potential utility of gallium in treating <i>P. mirabilis</i> infections.</p>

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Inhibition of Proteus mirabilis growth through gallium-based disruption of iron and heme metabolism

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Devendra Kumar,
  • Jack G. Hirz,
  • Seoung-Ryoung Choi,
  • John S. Stevenson,
  • Prabagaran Narayanasamy,
  • Bradley E. Britigan,
  • Jason E. Michaud

摘要

The increased incidence of multi-drug resistant (MDR) Proteus mirabilis highlights the need for novel antibiotics targeting P. mirabilis. In this study, we examined the potential antibacterial effects of gallium-based antimicrobials on P. mirabilis. We performed in vitro susceptibility testing of gallium compounds against P. mirabilis UTI isolates. Ga(NO3)3 and gallium protoporphyrin IX (GaPP) effectively inhibited P. mirabilis growth, with minimum inhibitory concentrations (MIC) of 64 μg/ml and 2.5 μg/ml, respectively. To further assess the effects of gallium compounds on P. mirabilis growth we performed time-kill assays. Ga(NO3)3 was bacteriostatic and prevented P. mirabilis growth over time, while GaPP was bactericidal, effectively killing P. mirablis over time. Free iron in the form of ferric ammonium citrate (FAC) reversed the inhibitory effects of Ga(NO3)3, while the addition of hemin reversed the effects of GaPP on P. mirabilis growth. In vivo, GaPP administered intravesically to the bladder reduced bacterial burden in an animal model of P. mirabilis urinary tract infection. Our results demonstrate that Ga(NO3)3 and GaPP disrupt free iron/heme and siderophore-based iron acquisition in P. mirabilis to inhibit growth. Further work is needed to better determine the effectiveness of gallium in vivo and the potential utility of gallium in treating P. mirabilis infections.