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Role of Bacteria in Urinary Tract Infections
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
JebaMercy Gnanasekaran, Kannan Balaji, K. Balamurugan
According to Sifiri et al. (2003). S. aureus infects C. elegans, ultimately leading to worm death, and key aspects of S. aureus pathogenesis and interaction with the innate immune system have been mechanistically conserved from nematodes through vertebrates. C. elegans will be a great model to study the novel staphylococcal genes required for the mammalian pathogenesis and host innate immune defense systems (Sifri et al., 2003). Death in C. elegans is mainly due to the disruption of the gut epithelium and assault of the internal organs by the invading pathogen (Garsin et al., 2003; Sifri et al., 2003; Irazoqui et al., 2010). Deformed anal region (Dar) was identified in S. aureus infection and is mainly relying on both β-catenin and MAPK pathways (Irazoqui et al., 2010). S. aureus requires protease and alpha-hemolysin for the pathogenesis in C. elegans (Sifri et al., 2003). The p38 MAPK and the catenin pathways are required for the host immune system against S. aureus. The significance of this pathway in S. aureus pathogenesis is comparable in higher vertebrates, where catenin activates NFκB-mediated immune gene expression.
Uropathogens and the Lower Urinary Tract
Published in Linda Cardozo, Staskin David, Textbook of Female Urology and Urogynecology - Two-Volume Set, 2017
leAd to AlterAtions in host response to pAthogens [23]. In the Urinary trAct, severAl tLr polymorphisms Are AssociAted with either increAsed susceptibility to or greAter protection from UTI As well As number of UTI episodes [24]. There Are severAl known toxins thAt modulAte the host inflAmmAtory response, induce cytopAthic effects, And cAuse tissue dAmAge. AlphA-hemolysin promotes cell lysis, AppeArs to AttenuAte the host inflAmmAtory response, And is AssociAted with clinicAl severity [25,26]. Cytotoxic necrotizing fActor 1 (CnF1) hAs been shown to cAuse membrAne chAnges thAt fAcilitAte bActeriAl internAlizAtion into host cells [27] And inhibit neutrophil Activity in AnimAl models [28]. Iron is required for bActeriAl cellulAr processes And survivAl, And the competition for AvAilAble iron stores highlights the impressive Ability of uPeC to evAde host defenses. one host defense is to limit iron AvAilAbility viA trAnsferrin, An iron cArrier protein thAt cAn move iron stores in And out of cells. However, uPeC cAn utilize enterobActin, which hAs A higher Affinity for iron thAn trAnsferrin And cAn therefore scAvenge iron from the environment [29]. An AdditionAl host protein cAlled lipocAlin 2 specificAlly binds enterobActin And is upregulAted in urotheliAl cells contAining uPeC [30,31]; however, uPeC hAve yet AdditionAl iron Acquisition systems thAt Are not recognized by lipocAlin And cAn therefore work Around this host defense As well [32].
Future Perspectives on Nucleic Acid Testing
Published in Attila Lorincz, Nucleic Acid Testing for Human Disease, 2016
Larry J. Kricka, Paolo Fortina
A nanopore provides the basis of a novel way of sequencing DNA.124 Alpha-hemolysin self-assembles in a lipid bilayer to form a nanopore with an internal diameter of 1.5 nm at its narrowest point. An electrical field can be used to draw a single strand of DNA through the pore, and as it traverses the pore, it modulates the ionic current flowing through the pore. The amplitude and duration of the blockade are dependent on the base composition of the DNA. It has been possible to obtain signatures characteristic of a nucleotide sequence. The next step for this technology is to refine the technique to distinguish single nucleotides.
Molecular characterization of Staphylococcus aureus isolates derived from severe pneumonia: a retrospective monocentre study
Published in Infectious Diseases, 2021
Maud Pichon, Maïte Micaelo, Saida Rasoanandrasana, Anne-Marie Menn
Although a necrotizing radiological pattern is more commonly associated with PVL-positive staphylococcal pneumonia [17], we described several cases of necrotizing pneumonia caused by PVL-negative S. aureus strains (strains N°1, 2, 4, 5, 7, 16) endowed with superantigens including toxin genes involved in the staphylococcal toxic shock such as tst, sea and sec. An overproduction of alpha-hemolysin (hla), a pore-forming toxin, was suggested to explain this radiological presentation in PVL-negative S. aureus strains [8]. More precisely, due to cytolytic properties, hla could act as a negative regulator of PVL expression and could modulate the expression of different virulence factors [10].
Recombinant ferritins for multimodal nanomedicine
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Yihao Li, Haoyu Gao, Eugenie Nepovimova, Qinghua Wu, Vojtech Adam, Kamil Kuca
Ftn-based nanoparticles designed for vaccination against SARS-COV-2/S25, influenzas and respiratory syncytial virus (RSV) induced high levels of specific antibodies in animals26 (Figure 1). A/Singapore/1/1957 haemagglutinin (HA) genetically fused to the Helicobacter pylori-derived Ftn (HP-Ftn) was shown to induce a broadly neutralising antibody response against influenza type 1 viruses (including seasonal H1 and avian H5 subtypes) 23. Furthermore, novel Coronavirus fusion Ftn was used to induce the production of neutralising antibodies in mice, and the induced antibody levels were twice higher than those of plasma donors in the recovery phase of SARS-COV-224. Furthermore, the fusion of HP-Ftn with Epstein-Bar virus (EBV) surface glycoprotein can stimulate mice and primates to produce specific neutralising antibodies higher than those induced by an EBV glycoprotein only27. The fusion Ftn nanoparticles produced by fusing the HP-Ftn with the H1N1 influenza virus HA induced a rapid production of neutralising antibodies in mice that were more than 10-fold more potent than those produced by the normal vaccine and even were able to neutralise different subtypes of the influenza virus28. As the H- and L- chains of Ftn can be combined with different antigens to prepare recombinant vaccination particles containing two or more antigens, Ftn also enables facile development of multivalent nanovaccines29. Staphylococcus aureus (SA) alpha-hemolysin is a frequent cause of deleterious cytotoxic effects of SA infections30. Therefore, a synthetic DNA encoding Hla121-138 was fused to the CDS of Ftn at the N-terminus, cloned into the pET-28A plasmid and introduced into BL21 (DE3) cells to express an epitope-based nanoparticle (EpNP) that immunologically induced potent haemolytic neutralising antibodies and conferred significant protection in a mouse model of SA skin infection31.
The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization
Published in Gut Microbes, 2022
Landry L. Tsoumtsa Meda, Luce Landraud, Serena Petracchini, Stéphane Descorps-Declere, Emeline Perthame, Marie-Anne Nahori, Laura Ramirez Finn, Molly A. Ingersoll, Rafael Patiño-Navarrete, Philippe Glaser, Richard Bonnet, Olivier Dussurget, Erick Denamur, Amel Mettouchi, Emmanuel Lemichez
We next analyzed the distribution of cnf1-positive strains in E. coli ST131 phylogeny (n = 725, cnf1-positive E. coli) (Figure 2a, black stripes). The cnf1-positive strains were preferentially associated with subclade C2 (n = 520) (p < 2.2 10−16, Chi-square association test), as compared to subclade C1 (n = 101), clade B (n = 72), or clade A (n = 32) (Figure 2a). Strikingly, most cnf1-positive strains segregated into lineages in all clades and subclades with a noticeable distribution of cnf1-positive ST131 strains in two large lineages (LL) in H30R/C1 (n = 101 cnf1-positive strains/107 strains in CNF1_LL1) and in H30Rx/C2_1 (n = 396 cnf1-positive strains/425 strains in the CNF1_LL2) (Figure 2a). We then analyzed the diversity of cnf1 alleles to define their distribution in the phylogeny of ST131 (Sup. Table S1). A similar analysis was performed with the alpha-hemolysin encoding gene, hlyA. We found a wide co-distribution of one combination of alleles of cnf1 (allele P1cnf1, 85,1%) and hlyA (allele P1hlyA, 77,2%) in E. coli ST131 clade A and C, whereas strains from clade B displayed a large range of combinations of various alleles (Sup. Figure S2a). Together, our data point to a clonal expansion of worldwide disseminated ST131-H30 strains with the same allele of cnf1. This prompted us to perform a clustering analysis of ST131-H30 strains according to their accessory gene contents. We generated a pan-genome matrix of 51,742 coding sequences from the n = 3,981 strains of clade C. The dataset of accessory genes was built from n = 7,678 sequences that were present in at least 50 and no more than 3,931 strains. We conducted a hierarchical clustering of strains and retained 10 distinct accessory gene clusters. Strikingly, this revealed a conservation between phylogenetically defined groups CNF1_LL1 and CNF1_LL2 and groups defined by their accessory gene contents (Figure 2b). Indeed, the hierarchical clustering was most evident for CNF1_LL2, showing a differential enrichment determined with Scoary of n = 1,434 genes as compared to other strains from clade C (P < 0.05, Bonferroni-adjusted correction). Together, these data point toward intensive group-specific diversification of accessory gene content in cnf1-positive clusters in ST131-H30.