Acinetobacter baumannii Biofilm Formation in Human Serum and Disruption by Gallium.

Biofilm-associated infections caused by Acinetobacter baumannii are extremely recalcitrant to antibiotic treatment. We report that A. baumannii develops a mature biofilm when grown in complement-free human serum (HS).

Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection.

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation.

Biological Characterization and in Vivo Assessment of the Activity of a New Synthetic Macrocyclic Antifungal Compound.

We recently identified a novel family of macrocyclic amidinoureas showing potent antifungal activity against Candida spp. In this study, we demonstrate the fungicidal effect of these compounds as well as their killing activity in a dose-dependent manner. Transcriptional analysis data indicate that our molecules induce a significant change in the transcriptome involving ATP binding cassette (ABC) transporter genes.

Cell aggregation promotes pyoverdine-dependent iron uptake and virulence in Pseudomonas aeruginosa.

In Pseudomonas aeruginosa the Gac signaling system and the second messenger cyclic diguanylate (c-di-GMP) participate in the control of the switch between planktonic and biofilm lifestyles, by regulating the production of the two exopolysaccharides Pel and Psl. The Gac and c-di-GMP regulatory networks also coordinately promote the production of the pyoverdine siderophore, and the extracellular polysaccharides Pel and Psl have recently been found to mediate c-di-GMP-dependent regulation of pyoverdine genes. Here we demonstrate that Pel and Psl are also essential for Gac-mediated activation of pyoverdine production.

Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P.

Iron and Acinetobacter baumannii Biofilm Formation.

Acinetobacter baumannii is an emerging nosocomial pathogen, responsible for infection outbreaks worldwide. The pathogenicity of this bacterium is mainly due to its multidrug-resistance and ability to form biofilm on abiotic surfaces, which facilitate long-term persistence in the hospital setting. Given the crucial role of iron in A.

Pyochelin potentiates the inhibitory activity of gallium on Pseudomonas aeruginosa.

Gallium (Ga) is an iron mimetic that has successfully been repurposed for antibacterial chemotherapy. To improve the antibacterial potency of Ga on Pseudomonas aeruginosa, the effect of complexation with a variety of siderophores and synthetic chelators was tested. Ga complexed with the pyochelin siderophore (at a 1:2 ratio) was more efficient than Ga(NO3)3 in inhibiting P.

Promises and failures of gallium as an antibacterial agent.

Gallium has a long history as a diagnostic and chemotherapeutic agent. The pharmacological properties of Ga(III) rely on chemical mimicry; when Ga(III) is exogenously supplied to living cells it can replace Fe(III) within target molecules, thereby perturbing bacterial metabolism. Ga(III)-induced metabolic distresses are dramatic in fast-growing cells, like bacterial cells.

Repurposing of gallium-based drugs for antibacterial therapy.

While the occurrence and spread of antibiotic resistance in bacterial pathogens is vanishing current anti-infective therapies, the antibiotic discovery pipeline is drying up. In the last years, the repurposing of existing drugs for new clinical applications has become a major research area in drug discovery, also in the field of anti-infectives. This review discusses the potential of repurposing previously approved gallium formulations in antibacterial chemotherapy.