Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host

Gao, Mengqi; Zhao, Tingting; Zhang, Chuanlong; Li, Ping; Wang, Jiazhe; Han, Jiatong; Zhang, Ning; Bo, Ping; Liu, Shiwei

doi:10.1016/j.biopha.2023.114859

Cited by 4 publications

(3 citation statements)

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“…Finally, the rpoS gene encodes an RNA polymerase factor, which was not identified in strain CFT073, and the sigA gene, which is an autotransporter, was identified exclusively in strain UTI-2_245U. The siderophores and regulatory factors presented by strains UTI-1_774U, UTI-2_245U, and UTI-3_455U could contribute, in an important way, to chronicity in the urinary tract ( Hunstad et al, 2005 ; Hryckowian and Welch, 2013 ; Gao et al, 2023 ). The absence of mobility, a critical factor in the rise of UPEC, to the upper urinary tract suggests an adaptation to the lower urinary tract.…”

Section: Discussionmentioning

confidence: 99%

Comparative genomic analysis of uropathogenic Escherichia coli strains from women with recurrent urinary tract infection

Flores-Oropeza,

Ochoa,

Cruz-Córdova

et al. 2024

Front. Microbiol.

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IntroductionRecurrent urinary tract infections (RUTIs) caused by uropathogenic Escherichia coli are costly public health problems impacting patients’ quality of life.AimIn this work, a comparative genomics analysis of three clinical RUTI strains isolated from bladder biopsy specimens was performed.Materials and methodsOne hundred seventy-two whole genomes of urinary tract E. coli strains were selected from the NCBI database. The search for virulence factors, fitness genes, regions of interest, and genetic elements associated with resistance was manually carried out. The phenotypic characterization of antibiotic resistance, haemolysis, motility, and biofilm formation was performed. Moreover, adherence and invasion assays with human bladder HTB-5 cells, and transmission electron microscopy (TEM) were performed.ResultsThe UTI-1_774U and UTI-3_455U/ST1193 strains were associated with the extraintestinal pathotypes, and the UTI-2_245U/ST295 strain was associated with the intestinal pathotype, according to a phylogenetic analysis of 172 E. coli urinary strains. The three RUTI strains were of clinical, epidemiological, and zoonotic relevance. Several resistance genes were found within the plasmids of these strains, and a multidrug resistance phenotype was revealed. Other virulence genes associated with CFT073 were not identified in the three RUTI strains (genes for type 1 and P fimbriae, haemolysin hlyA, and sat toxin). Quantitative adherence analysis showed that UTI-1_774U was significantly (p < 0.0001) more adherent to human bladder HTB-5 cells. Quantitative invasion analysis showed that UTI-2_245U was significantly more invasive than the control strains. No haemolysis or biofilm activity was detected in the three RUTI strains. The TEM micrographs showed the presence of short and thin fimbriae only in the UTI-2_245U strain.ConclusionThe high variability and genetic diversity of the RUTI strains indicate that are a mosaic of virulence, resistance, and fitness genes that could promote recurrence in susceptible patients.

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Section: Discussionmentioning

confidence: 99%

Comparative genomic analysis of uropathogenic Escherichia coli strains from women with recurrent urinary tract infection

Flores-Oropeza,

Ochoa,

Cruz-Córdova

et al. 2024

Front. Microbiol.

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“…These are metalloenzymes, which require metals including iron, nickel, zinc and copper as co-factors, with iron being the most commonly required [ 151 ]. As iron is a key factor in the proliferation of UPEC within the urinary tract, and the retention of iron to deprive invading pathogens of the nutrient composes part of the defensive strategy on the part of the host, acquisition of iron is a key point of competition between host and pathogen [ 152 , 153 , 154 ]. UPEC have evolved several iron acquisition systems in response to this competition, the first being iron-chelating molecules called siderophores, of which there are four that UPEC can synthesis and secrete, those being enterobactin, salmochelin, yersiniabactin, and aerobactin [ 155 ].…”

Section: Virulence Factorsmentioning

confidence: 99%

Uropathogenic Escherichia coli (UPEC)-Associated Urinary Tract Infections: The Molecular Basis for Challenges to Effective Treatment

Whelan,

Lucey,

Finn

2023

Microorganisms

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Urinary tract infections (UTIs) are among the most common bacterial infections, especially among women and older adults, leading to a significant global healthcare cost burden. Uropathogenic Escherichia coli (UPEC) are the most common cause and accounts for the majority of community-acquired UTIs. Infection by UPEC can cause discomfort, polyuria, and fever. More serious clinical consequences can result in urosepsis, kidney damage, and death. UPEC is a highly adaptive pathogen which presents significant treatment challenges rooted in a complex interplay of molecular factors that allow UPEC to evade host defences, persist within the urinary tract, and resist antibiotic therapy. This review discusses these factors, which include the key genes responsible for adhesion, toxin production, and iron acquisition. Additionally, it addresses antibiotic resistance mechanisms, including chromosomal gene mutations, antibiotic deactivating enzymes, drug efflux, and the role of mobile genetic elements in their dissemination. Furthermore, we provide a forward-looking analysis of emerging alternative therapies, such as phage therapy, nano-formulations, and interventions based on nanomaterials, as well as vaccines and strategies for immunomodulation. This review underscores the continued need for research into the molecular basis of pathogenesis and antimicrobial resistance in the treatment of UPEC, as well as the need for clinically guided treatment of UTIs, particularly in light of the rapid spread of multidrug resistance.

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“…Lastly, IRPs were shown to restrict bacterial iron access and promote iron scavenging via LCN2 in macrophages ( 159 ). In iron overload and limited conditions, IRPs detach or bind iron-responsive elements (IRE) on key genes involved in iron metabolism, and thus reduce iron export/import, utilization, and storage according to the underlying pathophysiological conditions or body needs ( 160 , 161 ). Similarly, IRP1 has been reported to induce the production of Tsf receptors in host cells when challenged with Toxoplasma gondii .…”

Section: Host Iron Regulation During Pathogen Attackmentioning

confidence: 99%

Key players in the regulation of iron homeostasis at the host-pathogen interface

Ullah,

Lang

2023

Front. Immunol.

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Iron plays a crucial role in the biochemistry and development of nearly all living organisms. Iron starvation of pathogens during infection is a striking feature utilized by a host to quell infection. In mammals and some other animals, iron is essentially obtained from diet and recycled from erythrocytes. Free iron is cytotoxic and is readily available to invading pathogens. During infection, most pathogens utilize host iron for their survival. Therefore, to ensure limited free iron, the host’s natural system denies this metal in a process termed nutritional immunity. In this fierce battle for iron, hosts win over some pathogens, but others have evolved mechanisms to overdrive the host barriers. Production of siderophores, heme iron thievery, and direct binding of transferrin and lactoferrin to bacterial receptors are some of the pathogens’ successful strategies which are highlighted in this review. The intricate interplay between hosts and pathogens in iron alteration systems is crucial for understanding host defense mechanisms and pathogen virulence. This review aims to elucidate the current understanding of host and pathogen iron alteration systems and propose future research directions to enhance our knowledge in this field.

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Ferritinophagy-mediated iron competition in RUTIs: Tug-of-war between UPEC and host

Cited by 4 publications

References 123 publications

Comparative genomic analysis of uropathogenic Escherichia coli strains from women with recurrent urinary tract infection

Comparative genomic analysis of uropathogenic Escherichia coli strains from women with recurrent urinary tract infection

Uropathogenic Escherichia coli (UPEC)-Associated Urinary Tract Infections: The Molecular Basis for Challenges to Effective Treatment

Key players in the regulation of iron homeostasis at the host-pathogen interface

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