Acinetobacter baumannii is an important nosocomial pathogen. Mechanisms that allow A. baumannii to cause human infection are still poorly understood. Iron is an essential nutrient for bacterial growth in vivo, and the multiplicity of iron uptake systems in A. baumannii suggests that iron acquisition contributes to the ability of A. baumannii to cause infection. In Gram-negative bacteria, active transport of ferrisiderophores and heme relies on the conserved TonB-ExbB-ExbD energytransducing complex, while active uptake of ferrous iron is mediated by the Feo system. The A. baumannii genome invariably contains three tonB genes (tonB1, tonB2, and tonB3), whose role in iron uptake is poorly understood. Here, we generated A. baumannii mutants with knockout mutations in the feo and/or tonB gene. We report that tonB3 is essential for A. baumannii growth under iron-limiting conditions, whereas tonB1, tonB2, and feoB appear to be dispensable for ferric iron uptake. tonB3 deletion resulted in reduced intracellular iron content despite siderophore overproduction, supporting a key role of TonB3 in iron uptake. In contrast to the case for tonB1 and tonB2, the promoters of tonB3 and feo contain functional Fur boxes and are upregulated in iron-poor media. Both TonB3 and Feo systems are required for growth in complement-free human serum and contribute to resistance to the bactericidal activity of normal human serum, but only TonB3 appears to be essential for virulence in insect and mouse models of infection. Our findings highlight a central role of the TonB3 system for A. baumannii pathogenicity. Hence, TonB3 represents a promising target for novel antibacterial therapies and for the generation of attenuated vaccine strains.
Acinetobacter baumannii is an emerging nosocomial pathogen, responsible for infection outbreaks worldwide. The pathogenicity of this bacterium is mainly due to its multidrug-resistance and ability to form biofilm on abiotic surfaces, which facilitate long-term persistence in the hospital setting. Given the crucial role of iron in A. baumannii nutrition and pathogenicity, iron metabolism has been considered as a possible target for chelation-based antibacterial chemotherapy. In this study, we investigated the effect of iron restriction on A. baumannii growth and biofilm formation using different iron chelators and culture conditions. We report substantial inter-strain variability and growth medium-dependence for biofilm formation by A. baumannii isolates from veterinary and clinical sources. Neither planktonic nor biofilm growth of A. baumannii was affected by exogenous chelators. Biofilm formation was either stimulated by iron or not responsive to iron in the majority of isolates tested, indicating that iron starvation is not sensed as an overall biofilm-inducing stimulus by A. baumannii. The impressive iron withholding capacity of this bacterium should be taken into account for future development of chelation-based antimicrobial and anti-biofilm therapies.
In his Democratic justice and the social contract, Weale presents a distinctive contingent practice-dependent model of ‘democratic justice’ that relies heavily on a condition of just social and political relations among equals. Several issues arise from this account. Under which conditions might such just social and political relations be realised? What ideal of equality is required for ‘democratic justice’? What are its implications for the political ideal of citizenship? This paper focuses on these questions as a way to critically reconsider Weale’s model. After presenting Weale’s procedural constructivism, I distinguish his model from an institutional practice-dependent model, one salient example of which is Rawls’s political constructivism. This distinction allows for a formulation of the social and political equality required for justice in each case. The contingent model assumes that an equality of ‘status’ will generate just social practices, yet it fails to recognise that an equality of ‘role’ is also important to ensure citizens’ compliance. The paper ultimately seeks to show that the contingent model is insufficient to ensure that just social practices will become stable
Encrusted cystitis is a severe chronic inflammatory disease of the bladder characterized by excessively alkaline urine and calcifications within the bladder wall. A case of a 60 year-old man affected by systemic lupus erythematosus (SLE), which developed encrusted cystitis due to Corynebacterium urealyticum with E. coli coinfection, shows that the treatment of encrusted cystitis with a endoscopic debulking of the encrusted stones and an antimicrobial therapy specific for C. urealyticum often is not sufficient for the complete resolution of symptoms.C. urealyticum is a Gram-positive, slow-growing, multiresistant, urease-positive microorganism with diphtheroid morphology. Since 1985 it has been known as a cause of alkaline encrusted cystitis and other urinary tract infections (1), occurring mainly in patients subjected to urological manipulation. Alkaline encrusted cystitis is a condition characterized by the deposition of inorganic salts on a damaged urothelium. The patient presents symptoms of cystitis (2). Moreover C. urealyticum has been involved in endocarditis, pneumonia, peritonitis, osteomyelitis and soft-tissue infections (3). We report a case of encrusted cystitis due to Corynebacterium urealyticum in a patient with SLE. MATERIALS AND METHODSA 60 year-old man, affected by SLE and in treatment with steroid therapy, presents with persistent symptoms of urinary tract infection including dysuria, pollakiuria, and intermittent hematuria with urinary gravel. He had undergone cystoscopy, which showed stone deposits in the bladder wall. Analysis of the urinary stone deposits on the bladder mucosa revealed the presence of ammonium magnesium phosphate (struvite) and calcium hydroxy phosphate (apatite).The urine sample was plated onto modified MacConkey agar (Oxoid) and CLED (cystine-Iactoseelectrolyte-deficient) agar and incubated at 37°C for 48 h. The identification and the antibiotic sensitivity testing for common pathogen germs were performed with the Phoenyx identification system (Becton Dickinson, USA). The urine and pus culture for Corynebacterium spp. on 7% sheep blood agar (Oxoid, England) was performed with incubation at 37°C in air for 24 h. The microbiological criteria for identification of C. urealyticum were the presence of gram-positive bacteria with diphtheroid morphology catalase-positive and strongly urease-positive. For identification the APICoryne identification strip (API Laboratory' Products; bio-Merieux, France) and the Phoenyx identification system (Becton Dickinson, USA) were utilised. The
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