A new metal scavenger for bacteria: All cells must find a way to acquire trace metals. Bacteria and plants scavenge iron, for instance, by synthesizing and releasing iron-chelating compounds called siderophores. Ghssein et al. describe three enzymes in Staphylococcus aureus that are responsible for the biosynthesis of another type of metallophore (see the Perspective by Nolan). Metabolomics and a range of biochemical assays show that this compound, named staphylopine, is involved in the uptake of a range of metals, depending on the growth environment. The genes required for staphylopine biosynthesis are conserved across a number of pathogenic bacteria and are similar to those for a broad-spectrum metallophore produced by plants. Science , this issue p. 1105 ; see also p. 1055

The opportunistic pathogen Klebsiella pneumoniae (K. pneumoniae) can colonize mucosal surfaces and spread from mucosae to other tissues, causing fatal infections. Medical equipment and the healthcare setting can become colonized by Klebsiella species, which are widely distributed in nature and can be found in water, soil, and animals. Moreover, a substantial number of community-acquired illnesses are also caused by this organism worldwide. These infections are characterized by a high rate of morbidity and mortality as well as the capacity to spread metastatically. Hypervirulent Klebsiella strains are thought to be connected to these infections. Four components are critical to this bacterium’s pathogenicity—the capsule, lipopolysaccharide, fimbriae, and siderophores. Siderophores are secondary metabolites that allow iron to sequester from the surrounding medium and transport it to the intracellular compartment of the bacteria. A number of variables may lead to K. pneumoniae colonization in a specific area. Risk factors for infection include local healthcare practices, antibiotic use and misuse, infection control procedures, nutrition, gender, and age.

P. aeruginosa is a common Gram-negative bacterium found in nature that causes severe infections in humans. As a result of its natural resistance to antibiotics and the ability of biofilm formation, the infection with this pathogen can be therapeutic challenging. During infection, P. aeruginosa produces secondary metabolites such as metallophores that play an important role in their virulence. Metallophores are metal ions chelating molecules secreted by bacteria, thus allowing them to survive in the host under metal scarce conditions. Pyoverdine, pyochelin and pseudopaline are the three metallophores secreted by P. aeruginosa. Pyoverdines are the primary siderophores that acquire iron from the surrounding medium. These molecules scavenge and transport iron to the bacterium intracellular compartment. Pyochelin is another siderophore produced by this bacterium, but in lower quantities and its affinity for iron is less than that of pyoverdine. The third metallophore, pseudopaline, is an opine narrow spectrum ion chelator that enables P. aeruginosa to uptake zinc in particular but can transport nickel and cobalt as well. This review describes all the aspects related to these three metallophore, including their main features, biosynthesis process, secretion and uptake when loaded by metals, in addition to the genetic regulation responsible for their synthesis and secretion.

Metal uptake is vital for all living organisms. In metal scarce conditions a common bacterial strategy consists in the biosynthesis of metallophores, their export in the extracellular medium and the recovery of a metal-metallophore complex through dedicated membrane transporters. Staphylopine is a recently described metallophore distantly related to plant nicotianamine that contributes to the broad-spectrum metal uptake capabilities of Staphylococcus aureus. Here we characterize a four-gene operon (PA4837–PA4834) in Pseudomonas aeruginosa involved in the biosynthesis and trafficking of a staphylopine-like metallophore named pseudopaline. Pseudopaline differs from staphylopine with regard to the stereochemistry of its histidine moiety associated with an alpha ketoglutarate moiety instead of pyruvate. In vivo, the pseudopaline operon is regulated by zinc through the Zur repressor. The pseudopaline system is involved in nickel uptake in poor media, and, most importantly, in zinc uptake in metal scarce conditions mimicking a chelating environment, thus reconciling the regulation of the cnt operon by zinc with its function as the main zinc importer under these metal scarce conditions.

Proteus mirabilis is a Gram-negative bacterium with exclusive molecular and biological features. It is a versatile pathogen acclaimed for its distinct urease production, swarming behavior, and rapid multicellular activity. Clinically, P. mirabilis is a frequent pathogen of the human urinary system where it causes urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs). This review explores the epidemiology, risk factors, clinical manifestations, and treatment of P. mirabilis infections, emphasizing its association with UTIs. The bacterium’s genome analysis revealed the presence of resistance genes against commonly used antibiotics, an antibiotic-resistant phenotype that poses a serious clinical challenge. Particularly, the emergence of extended-spectrum β-lactamases (ESBLs) and carbapenemases resistant P. mirabilis strains. On a molecular level, P. mirabilis possesses a wide array of virulence factors including the production of fimbriae, urease, hemolysins, metallophores, and biofilm formation. This review thoroughly tackles a substantial gap in understanding the role of metallophores in shaping the virulence factors of P. mirabilis virulence. Siderophores, iron metal chelating and transporting metallophores, particularly contribute to the complex pathogenic strategies, displaying a potential target for therapeutic intervention.