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Mechanism of iron acquisition by pyoverdine in Pseudomonas aeruginosa. Reprinted with permission from reference (Bonneau et al. 2020). Copyright 2020, Springer Nature
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Pseudmonas aeruginosa is a Gram-negative bacterium known to be ubiquitous and recognized as one of the leading causes of infections such as respiratory, urinary tract, burns, cystic fibrosis, and in immunocompromised individuals. Failure of antimicrobial therapy has been documented to be attributable due to the development of various resistance mec...
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... that, iron bound to the siderophores is reduced from Fe 3+ to Fe 2+ by a specialized enzyme and released from the siderophores ( Chu et al. 2010). Figure 1 depicts the iron uptake mechanism of the ferrisiderophore complex in the cytoplasm. In an iron-restricted environment, PVD is loaded onto the outer membrane transporter FpvA and subsequently transported across the P. aeruginosa outer membrane. ...Similar publications
Antimicrobial resistance (AMR) poses a critical global health threat, leading to approximately 1.27 million deaths annually from infectious diseases resistant to existing antibiotics. Factors such as antibiotic misuse and environmental contamination have accelerated AMR, with the COVID-19 pandemic exacerbating the issue due to increased antibiotic...
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... activities in animals and plants. Furthermore, emerging research priorities include exploring the genes involved in the synthesis and secretion of siderophores [96][97][98] and investigating the potential toxicity of these compounds [99][100][101]. These areas represent crucial international research interests, likely driving future studies. ...
... This clustered keyword distribution reveals a strong emphasis on microbial synthesis and secretion of siderophores, particularly through studies on E. coli [94,95], with a lesser focus on siderophore activities in animals and plants. Furthermore, emerging research priorities include exploring the genes involved in the synthesis and secretion of siderophores [96][97][98] and investigating the potential toxicity of these compounds [99][100][101]. These areas represent crucial international research interests, likely driving future studies. ...
Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions.
... Among them are the applications of siderophore from Pseudomonas aeruginosa as a corona in order to synthesize NPs as potential antibiofilm and antivirulence agents. Because the cell receptor and transport system can readily detect the siderophore, producing various types of NPs using the siderophore may also be identified by these receptor proteins and transport system, allowing the NPs to enter the cells and cause cell death [41]. Under iron-limiting conditions, P. aeruginosa regulates its nutrition mainly by two siderophores named pyoverdine (PVD) and pyochelin, which scavenge the iron from the environment to deliver inside the cells via membrane receptor-mediated. ...
The increasing incidence of antimicrobial resistance exhibited by biofilm-forming microbial pathogens has been recognized as one of the major issues in the healthcare sector. In the present study, nanomaterial-based controlling the biofilm and virulence properties has been considered an alternative approach. Pyoverdine (PVD) isolated from the Pseudomonas aeruginosa was utilized as a biological corona to synthesize silver nanoparticles (AgNPs), which will be helpful in a targeted action to microbial pathogens due to the recognition of the corona of the nanoparticles by the pathogenic membrane. Synthesized PVD-AgNPs were spherical to irregular, with an average size value of 251.87 ± 21.8 nm and zeta potential with a value of −36.51 ± 0.69 mV. The MIC value of PVD-AgNPs towards P. aeruginosa, Listeria monocytogenes, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans in the standard and host-mimicking media were observed in decreasing order in a multi-fold, such as standard growth media > sputum > synthetic human urine > saliva. Both the initial stage and the well-established biofilms of these microbial pathogens have been effectively inhibited and eradicated by PVD-AgNPs. PVD-AgNPs increase the susceptibility of tetracycline, PVD, and amphotericin B towards established mature mono- and mixed-species biofilms of S. aureus and C. albicans. Additionally, PVD-AgNPs attenuate several virulence properties, such as inhibition of protease activity, motility, and PVD and pyocyanin production in P. aeruginosa. The inhibition of gene expression of biofilm and virulence-associated genes in P. aeruginosa validates its phenotypic effects.
... In fact, the elevated reactivity of the soluble Fe 2+ ion for hydrogen peroxide and for oxygen, in general, leads to the production of highly reactive oxygen species (ROS), which culminates in the damage of essential cellular components causing oxidative stress and cellular death [26]. Pyoverdine is usually implicated in acute illness, but also in the production of mature biofilms, so its role in the progression of the disease is still unclear [27]. ...
The airways of cystic fibrosis (CF) patients are colonized by many pathogens and the most common is Pseudomonas aeruginosa, an environmental pathogen that is able to infect immunocompromised patients thanks to its ability to develop resistance to conventional antibiotics. Over 12% of all patients colonized by P. aeruginosa harbour multi-drug resistant species. During airway infection in CF, P. aeruginosa adopts various mechanisms to survive in a hostile ecological niche characterized by low oxygen concentration, nutrient limitation and high osmotic pressure. To this end, P. aeruginosa uses a variety of virulence factors including pigment production, biofilm formation, motility and the secretion of toxins and proteases. This study represents the first report that systematically analyzes the differences in virulence features, in normoxia and anoxia, of clinical P. aeruginosa isolated from CF patients, characterized by multi- or pan-drug antibiotic resistance compared to antibiotic sensitive strains. The virulence features, such as biofilm formation, protease secretion and motility, are highly diversified in anaerobiosis, which reflects the condition of chronic CF infection. These findings may contribute to the understanding of the real-world lifestyle of pathogens isolated during disease progression in each particular patient and to assist in the design of therapeutic protocols for personalized medicine.
... P. aeruginosa secretes pyoverdine (PvD) siderophores for high-affinity iron absorption (Figure 1i) (Perraud et al. 2022). PvD siderophores play pathogenic roles in P. aeruginosa as well as iron absorption (Díaz-Pérez et al. 2023;Jeong et al. 2023). PvD increases the production of protease and exotoxin A, both of which contribute to P. aeruginosa virulence (lopez-Medina et al. 2015). ...
Pseudomonas aeruginosa can efficiently adapt to changing environmental conditions due to its ubiquitous nature, intrinsic/acquired/adaptive resistance mechanisms, high metabolic versatility, and the production of numerous virulence factors. As a result, P. aeruginosa becomes an opportunistic pathogen, causing chronic infection in the lungs and several organs of patients suffering from cystic fibrosis. Biofilm established by P. aeruginosa in host tissues and medical device surfaces has been identified as a major obstruction to antimicrobial therapy. P. aeruginosais very likely to be closely associated with the various microorganisms in the host tissues or organs in a pathogenic or nonpathogenic behavior. Aside from host-derived molecules, other beneficial and pathogenic microorganisms produce a diverse range of secondary metabolites that either directly or indirectly favor the persistence of P. aeruginosa. thus, it is critical to understand how P. aeruginosa interacts with different molecules and ions in the host and abiotic environment to produce extracellular polymeric substances and virulence factors. thus, the current review discusses how various natural and synthetic molecules in the environment induce biofilm formation and the production of multiple virulence factors.
... Pseudomonas is a genus of ubiquitous Gram-negative γ-proteobacterium, the members of which are known for their capacity to colonize various ecological niches; in addition, they are highly versatile and adaptable [1][2][3]. This adaptability is considered to be associated with their diverse and highly elaborate siderophore systems [4][5][6][7]. Iron is an essential trace element for virtually all living organisms to maintain a normal life as it is involved in several key metabolic processes [8][9][10][11]. However, owing to its low solubility under physiological pH and aerobic conditions, iron is poorly bioavailable in the environment [12][13][14][15]. ...
The newly discovered iron scavenger 7-hydroxytropolone (7-HT) is secreted by Pseudomonas donghuensis HYS. In addition to possessing an iron-chelating ability, 7-HT has various other biological activities. However, 7-HT’s biosynthetic pathway remains unclear. This study was the first to report that the phenylacetic acid (PAA) catabolon genes in cluster 2 are involved in the biosynthesis of 7-HT and that two genes, paaZ (orf13) and ech, are synergistically involved in the biosynthesis of 7-HT in P. donghuensis HYS. Firstly, gene knockout and a sole carbon experiment indicated that the genes orf17–21 (paaEDCBA) and orf26 (paaG) were involved in the biosynthesis of 7-HT and participated in the PAA catabolon pathway in P. donghuensis HYS; these genes were arranged in gene cluster 2 in P. donghuensis HYS. Interestingly, ORF13 was a homologous protein of PaaZ, but orf13 (paaZ) was not essential for the biosynthesis of 7-HT in P. donghuensis HYS. A genome-wide BLASTP search, including gene knockout, complemented assays, and site mutation, showed that the gene ech homologous to the ECH domain of orf13 (paaZ) is essential for the biosynthesis of 7-HT. Three key conserved residues of ech (Asp39, His44, and Gly62) were identified in P. donghuensis HYS. Furthermore, orf13 (paaZ) could not complement the role of ech in the production of 7-HT, and the single carbon experiment indicated that paaZ mainly participates in PAA catabolism. Overall, this study reveals a natural association between PAA catabolon and the biosynthesis of 7-HT in P. donghuensis HYS. These two genes have a synergistic effect and different functions: paaZ is mainly involved in the degradation of PAA, while ech is mainly related to the biosynthesis of 7-HT in P. donghuensis HYS. These findings complement our understanding of the mechanism of the biosynthesis of 7-HT in the genus Pseudomonas.
... HTS is the most common way to identify antimicrobial agents based on the availability of large-scale chemical libraries [60] . Unlike conventional screening, HTS can identify active molecules and analyse the content and changes of target metabolites accordingly, enabling sensitive and accurate screening [61] . Indeed, unique patterns of WTA genes provide the basis for HTS to identify compounds targeting early or late stages of the WTA biosynthetic pathway [62] . ...
Wall teichoic acid (WTA) and lipoteichoic acid (LTA) are structural components of Gram-positive bacteria's peptidoglycan and cell membrane, which are mostly anionic glycopolymers. WTA confers numerous physiological, virulence, and pathogenic features to bacterial pathogens. It controls cell shape, cell division, and the localization of autolytic enzymes and ion homeostasis. In the context of virulence and pathogenicity, it aids bacterial cell attachment and colonization and protects against the host defense system and antibiotics. Having such a broad function in pathogenic bacteria's lifecycle, WTA/LTA become one of the potential targets for antibacterial agents to reduce bacterial infection in the host. The number of reports for targeting the WTA/LTA pathway has risen, mostly by focusing on three distinct targets: antivirulence targets, β-lactam potentiator targets, and essential targets. The current review looked at the role of WTA/LTA in biofilm development and virulence in a range of Gram-positive pathogenic bacteria. Furthermore, alternate strategies, such as the application of natural and synthetic compounds that target the WTA/LTA pathway, have been thoroughly discussed. Moreover, the application of nanomaterials and a combination of drugs have also been discussed as a viable method for targeting the WTA/LTA in numerous Gram-positive bacteria. In addition, a future perspective for controlling bacterial infection by targeting the WTA/LTA is proposed.
... The synthesis of these AI improves protein expression leading to an increase of factors involved in QS. Also, maturation of the biofilm is regulated by this feature, following irreversible attachment, production of virulence factors involved in P. aeruginosa pathogenicity, iron scavenging activity, motility, and dissemination [19,20]. ...
Food poisoning is one of the main problems affecting public health. Bacterial adhesion on surfaces has been documented for decades, and it is known that biofilm-forming bacteria are much more resistant than planktonic cells. Typically, nanosystems are studied regarding their antimicrobial activity (i.e., pathogenic bacteria such as Campylobacter, Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, Staphylococcus aureus, Clostridium perfringens, Bacillus cereus, and Yersinia enterocolitica), but not for antibiofilm activity and their associated genes. Some studies established protein-ligand prediction concerning quorum sensing suppression, commonly called quorum quenching. This chapter focuses on nanosystems or functionalized nanomaterials that have demonstrated antibiofilm or quorum quenching activity and, thus, establishes perspectives in modeling specific nanosystems to eradicate biofilms produced by foodborne pathogens.
... Moreover, its acquisition mechanisms have also evolved in C. albicans, allowing the fungus to acquire Zn from the host environment through manipulating proteins like Zn transporters and Zn-regulated transcription factors [150]. Cu is paramount for several biological processes in microbial pathogens, such as oxidative stress resistance, energy metabolism, and DNA synthesis, for example, the bacterial pathogen Pseudomonas aeruginosa requires Cu for siderophores and exotoxin expressions [151]. P. aeruginosa can also acquire Cu by producing Cu transporters and Cu-regulated transcription factors [152]. ...
... Cystic fibrosis (CF) is often accompanied with infections by the opportunistic pathogen Pseudomonas aeruginosa. Inhibition of its elastase enzymes and iron uptake by its siderophores-pyoverdins-could be valuable therapeutic targets [93]. The elastase produced by P. aeruginosa causes a rapid release of iron from transferrin and its uptake by pyoverdins, but LF is not a source of iron for these bacteria [94]. ...
In this article, we review the benefits of applying bovine colostrum (BC) and lactoferrin (LF) in animal models and clinical trials that include corticosteroid application and psychic stress, treatment with non-steroid anti-inflammatory drugs (NSAIDs) and antibiotics. A majority of the reported investigations were performed with native bovine or recombinant human LF, applied alone or in combination with probiotics, as nutraceutics and diet supplements. Apart from reducing adverse side effects of the applied therapeutics, BC and LF augmented their efficacy and improved the wellness of patients. In conclusion, LF and complete native colostrum, preferably administered with probiotic bacteria, are highly recommended for inclusion in therapeutic protocols in NSAIDs and corticosteroid anti-inflammatory, as well as antibiotic, therapies. These colostrum-based products can also be of value for individuals subjected to prolonged psychophysical stress (mediated by endogenous corticosteroids), especially at high ambient temperatures (soldiers and emergency services), as well as physically active people and training athletes. They are also recommended for patients during recovery from trauma and surgery, which are always associated with severe psychophysical stress.
