Overview of Proteus mirabilis pathogenicity and virulence. Insights into the role of metals.

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 ß-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.

General Overview of Klebsiella pneumonia: Epidemiology and the Role of Siderophores in Its Pathogenicity.

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.

Towards new antibiotics classes targeting bacterial metallophores.

The increasing bacterial resistance caused by antibiotic overuse has promoted the search for new antimicrobial strategies. Metals uptake via bacterial metallophores are studied to develop new therapeutics against infectious diseases, because metal ions are essential for bacterial growth and virulence. Metal ions assimilation is mainly dependent on metallophores production which are metal chelators synthetized and produced by bacteria to facilitate metals uptake and are vital for bacterial pathogenicity. Here we highlight the perspective for antimicrobial and therapeutic potential of metallophores through several approaches for metallophores application in antimicrobial therapy.

Overview of Yersinia pestis Metallophores: Yersiniabactin and Yersinopine.

The pathogenic anaerobic bacteria Yersinia pestis (Y. pestis), which is well known as the plague causative agent, has the ability to escape or inhibit innate immune system responses, which can result in host death even before the activation of adaptive responses. Bites from infected fleas in nature transmit Y. pestis between mammalian hosts causing bubonic plague. It was recognized that a host's ability to retain iron is essential in fighting invading pathogens. To proliferate during infection, Y. pestis, like most bacteria, has various iron transporters that enable it to acquire iron from its hosts. The siderophore-dependent iron transport system was found to be crucial for the pathogenesis of this bacterium. Siderophores are low-molecular-weight metabolites with a high affinity for Fe3+. These compounds are produced in the surrounding environment to chelate iron. The siderophore secreted by Y. pestis is yersiniabactin (Ybt). Another metallophore produced by this bacterium, yersinopine, is of the opine type and shows similarities with both staphylopine and pseudopaline produced by Staphylococcus aureus and Pseudomonas aeruginosa, respectively. This paper sheds light on the most important aspects of the two Y. pestis metallophores as well as aerobactin a siderophore no longer secreted by this bacterium due to frameshift mutation in its genome.

Zinc Removal from Water via EDTA-Modified Mesoporous SBA-16 and SBA-15.

The removal of zinc ions from water was investigated using two types of ordered mesoporous silica (SBA-15 and SBA-16). Both materials were functionalized with APTES (3-aminopropyltriethoxy-silane) and EDTA (ethylenediaminetetraacetic acid) through post grafting methods. The modified adsorbents were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), X-ray diffraction (XRD), nitrogen (N2) adsorption-desorption analysis, Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis. The ordered structure of the adsorbents was conserved after modification. SBA-16 was found to be more efficient than SBA-15 owing to its structural characteristics. Different experimental conditions were examined (pH, contact time, and initial zinc concentration). The kinetic adsorption data followed the pseudo-second-order model indicating favorable adsorption conditions. The intra-particle diffusion model plot represented a two-stage adsorption process. The maximum adsorption capacities were calculated by the Langmuir model. The adsorbent can be regenerated and reused several times without a significant decline in adsorption efficiency.

A Review of Pseudomonas aeruginosa Metallophores: Pyoverdine, Pyochelin and Pseudopaline.

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.

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

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.