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Inflammation and Infection
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Judith Hall, Christopher K. Harding
P. mirabilis urease is expressed during growth in urine:Hydrolysis of urea to carbon dioxide and ammonia.Creates alkaline urine → calcium crystal (apatite) formation and magnesium ammonium phosphate precipitates (struvite)Crystals become trapped within polysaccharides produced by attached bacterial cells → crystalline biofilms on tissues/cathetersAmmonia is toxic to urothelial cells.The urinary tract is limited in iron (an essential element for bacterial growth).Uropathogens synthesise siderophores to scavenge, chelate, and transport iron (Fe3+).Siderophores synthesised include the proteins aerobactin, yersiniabactin, and enterobactin.
Epidemiology of Acinetobacter spp.: Surveillance and Management of Outbreaks
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
M.-L. Joly-Guillou, C. Brun-Buisson
Iron acquisition — >The ability of a bacterium to obtain the neces-sary iron for growth in the human body is an important virulence determinant. Some strains of Acinetobacter have been shown to produce siderophores, such as aerobactin, and iron-repressible outer-membrane receptor proteins (Smith et al., 1990; Echenique et al., 1992; Actis et al., 1993). However, no aerobactin-producing strains were identified among 50 Acinetobacter clinical isolates studied by Martinez et al. (1987).
Urinary Tract Infection
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
To be successful, any invading microorganism will require an adequate supply of nutrients. In particular, free iron is required for metabolism and multiplication of E. coli, iron uptake being facilitated by the siderophore aerobactin and enterobactin (21). The ability to produce these agents thus confirms an advantage on strains invading the urinary tract, and an association has been observed between aerobactin production and the expression of P fimbriae (see below) in patients with symptomatic UTI (24).
Global spread and evolutionary convergence of multidrug-resistant and hypervirulent Klebsiella pneumoniae high-risk clones
Published in Pathogens and Global Health, 2023
Gabriele Arcari, Alessandra Carattoli
Genomic studies performed on NDM-producing ST147 from Italy revealed that they belonged to the KL64 clade and that they were related with clinical isolates from the Middle East, the USA, Thailand, Myanmar, Egypt, Lebanon, the UK, Denmark, Germany, and Hungary [111]. In Italian ST147, virulence genes encoding aerobactin (iutA-iucABCD), regulators of the mucoid phenotype (rmpADC and rmpA2, the latter often carrying a frameshift mutation), proteins involved in iron metabolism (cobW), and hemin and lysine transport system (shiF) were located on a large hybrid virulence/resistance plasmid carrying the HIB-FIB (Mar) replicons. This also carried blaCTX-M-15 and the 16S methyltransferase armA genes. The origin of the hybrid virulence/resistance plasmid can be traced back to the pNDM-Mar plasmid, carrying the same IncFIB/IncHI1 replicons (IncHI1B_pNDM-Mar; IncFIB_pNDM-Mar JN420336), identified in 2011 in K. pneumoniae ST15 from Morocco. pNDM-Mar was positive for the blaNDM-1, blaCTX-M-15 and qnrB1 genes, but negative for virulence genes [112]. The virulence content probably originates from the pK2044 and pLVpK virulence plasmids of hvKp that are characterized by the replicon IncHI1B_pNDM-Mar but carry a different FIB-like replicon (repB_KLEB_VIR_AP006726).
Hypervirulence and carbapenem resistance: two distinct evolutionary directions that led high-risk Klebsiella pneumoniae clones to epidemic success
Published in Expert Review of Molecular Diagnostics, 2019
Yi-Chyi Lai, Min-Chi Lu, Po-Ren Hsueh
During infection, K. pneumoniae releases siderophores, which are small but high-affinity iron-chelating compounds, to chelate iron away from transferrin and lactoferrin, and form soluble Fe3+ complexes that can be actively transported into bacterial cells. Four types of siderophores, enterobactin, yersiniabactin, salmochelin, and aerobactin, have been identified in K. pneumoniae. Both the classical K. pneumoniae and HvKP express enterobactin. However, lipocalin-2 (neutrophil gelatinase-associated lipocalin), a protein stored in the granules of human neutrophils, sequesters enterobactin that in turn inhibits the growth of K. pneumoniae strains producing enterobactin as the only type of siderophore [54]. In addition to enterobactin, most of the HvKP strains express the other three types of siderophores. Yersiniabactin, aerobactin, and salmochelin, encoded by the irp-ybt-fyu, iucABCDiutA, and iroBCDN loci, respectively, are impervious to lipocalin-2 neutralization, and thus allow HvKP to grow to high bacterial loads during infection [55]. Using isogenic mutants, Russo et al. demonstrated that HvKP produced aerobactin as the primary type of siderophore under in vivo iron-limiting conditions. The production of aerobactin, but not yersiniabactin or salmochelin, was required for the full virulence of HvKP1 (ST86, K2-type HvKP) in intraperitoneal and subcutaneous infection mouse models [56].
Progress towards the development of Klebsiella vaccines
Published in Expert Review of Vaccines, 2019
Myeongjin Choi, Sharon M Tennant, Raphael Simon, Alan S Cross
Siderophores, such as aerobactin and enterochelin, are small iron-binding proteins that enable the host to compete for the iron that is necessary for growth. Iron-uptake is dependent on a family of proteins that includes a TonB outer membrane receptor that mediates the transport of iron into the periplasm [44]. The TonB system plays an important role in virulence as TonB mutants are less virulent. Independent of the role of siderophores on bacterial growth, they appear to also modify host immune responses including cytokine secretion, inflammatory gene expression and activation of hypoxia inducible factor-1α (HIF-1α), a master transcription factor that controls vascular permeability and inflammatory gene expression [45]. Hypervirulent KP K1 strains have been associated with increased siderophore activity [10].