The Key Element Role of Metallophores in the Pathogenicity and Virulence of Staphylococcus aureus: A Review

SIMPLE SUMMARY: Metallophores, which are secondary metabolites secreted by bacteria, play an important role in their virulence. The bacterium Staphylococcus aureus produces several types of metallophores, such as staphyloferrin A, staphyloferrin B, and staphylopine, which are responsible for metal ion sequestering. The former is specific for iron chelating, while the latter is a wide-spectrum metallophore, but it mainly chelates zinc. The detailed description of the biosynthesis, export and import processes of each metallophore type is highlighted in this review. Moreover, the genetic regulation is explained as well. Previous studies that provide evidence about the crucial part of metallophores in Staphylococcus aureus pathogenesis were also mentioned herein. ABSTRACT: The ubiquitous bacterium Staphylococcus aureus causes many diseases that sometimes can be fatal due to its high pathogenicity. The latter is caused by the ability of this pathogen to secrete secondary metabolites, enabling it to colonize inside the host causing infection through various processes. Metallophores are secondary metabolites that enable bacteria to sequester metal ions from the surrounding environment since the availability of metal ions is crucial for bacterial metabolism and virulence. The uptake of iron and other metal ions such as nickel and zinc is one of these essential mechanisms that gives this germ its virulence properties and allow it to overcome the host immune system. Additionally, extensive interactions occur between this pathogen and other bacteria as they compete for resources. Staphylococcus aureus has high-affinity metal import pathways including metal ions acquisition, recruitment and metal–chelate complex import. These characteristics give this bacterium the ability to intake metallophores synthesized by other bacteria, thus enabling it to compete with other microorganisms for the limited nutrients. In scarce host conditions, free metal ions are extremely low because they are confined to storage and metabolic molecules, so metal ions are sequestered by metallophores produced by this bacterium. Both siderophores (iron chelating molecules) and staphylopine (wide- spectrum metallophore) are secreted by Staphylococcus aureus giving it infectious properties. The genetic regulation of the synthesis and export together with the import of metal loaded metallophores are well established and are all covered in this review.