82 research outputs found

    Biofilm producing Salmonella typhi: Chronic colonization and development of gallbladder cancer

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    Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention

    How human papillomavirus replication and immune evasion strategies take advantage of the host DNA damage repair machinery

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    The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM-and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)-STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses

    Campylobacter jejuni fatal sepsis in a patient with non-Hodgkin’s lymphoma: Case report and literature review of a difficult diagnosis

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    Campylobacter jejuni (C. jejuni) bacteremia is difficult to diagnose in individuals with hematological disorders undergoing chemotherapy. The cause can be attributed to the rarity of this infection, to the variable clinical presentation, and to the partial overlapping symptoms underlying the disease. Here, we report a case of a fatal sepsis caused by C. jejuni in a 76-year-old Caucasian man with non-Hodgkin's lymphoma. After chemotherapeutic treatment, the patient experienced fever associated with severe neutropenia and thrombocytopenia without hemodynamic instability, abdominal pain, and diarrhea. The slow growth of C. jejuni in the blood culture systems and the difficulty in identifying it with conventional biochemical phenotyping methods contributed to the delay of administering a targeted antimicrobial treatment, leading to a fatal outcome. Early recognition and timely intervention are critical for the successful management of C. jejuni infection. Symptoms may be difficult to recognize in immunocompromised patients undergoing chemotherapy. Thus, it is important to increase physician awareness regarding the clinical manifestations of C. jejuni to improve therapeutic efficacy. Moreover, the use of more aggressive empirical antimicrobial treatments with aminoglycosides and/or carbapenems should be considered in immunosuppressed patients, in comparison to those currently indicated in the guidelines for cancer-related infections supporting the use of cephalosporins as monotherapy

    The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis

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    Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia, respectively. The infection affects multiple organ systems, including the skin, joints, and the nervous system. Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease, occurring in 10-15% of infected individuals. During the course of the infection, bacteria migrate through the host tissues altering the coagulation and fibrinolysis pathways and the immune response, reaching the central nervous system (CNS) within 2 weeks after the bite of an infected tick. The early treatment with oral antimicrobials is effective in the majority of patients with LNB. Nevertheless, persistent forms of LNB are relatively common, despite targeted antibiotic therapy. It has been observed that the antibiotic resistance and the reoccurrence of Lyme disease are associated with biofilm-like aggregates in B. burgdorferi, B. afzelii, and B. garinii, both in vitro and in vivo, allowing Borrelia spp. to resist to adverse environmental conditions. Indeed, the increased tolerance to antibiotics described in the persisting forms of Borrelia spp., is strongly reminiscent of biofilm growing bacteria, suggesting a possible role of biofilm aggregates in the development of the different manifestations of Lyme disease including LNB

    Comment on “Intravitreal Ampicillin Sodium for Antibiotic-Resistant Endophthalmitis: Streptococcus uberis

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    In the paper by Velez-Montoya et al. [1], the authors reported the first description of a case of intraocular infection in humans caused by an antibiotic-resistant strain of Streptococcus uberis. We would like to point out that the absence of any description of the method used for bacteria identification in this paper raises some concerns related to the possibility of a misidentification of this bacterium as a pathogen affecting the human eye

    Release of Palladium from Biomechanical Prostheses in Body Fluids Can Induce or Support PD-Specific IFNγ T Cell Responses and the Clinical Setting of a Palladium Hypersensitivity:

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    The increased use of Palladium (Pd) for biomedical applications, which has more than doubled in the last ten years, appears to be associated with an increased frequency of adverse reactions to Pd. The aim of this study is to investigate the relationship between the implant of a biomechanical apparatus containing Pd and the setting of a hypersensitivity to Pd by determining the levels of the metal released in biological fluids, assessing the effects of Pd on peripheral blood mononuclear cell (PBMC) cytokine production and exploring the clinical setting of skin sensitization. Of a total of 3,093 subjects examined in 2006, sensitization to Pd alone or in association with nickel (Ni) was observed in 1.6% and 13.03% of the individuals, respectively. Of these, a group of six subjects positive to Pd and negative to Ni at patch testing were selected on the basis of the oral clinical symptoms in order to measure both the levels of Pd in biological fluids and the degradation of the dental prostheses. Specific Pd measurements were carried out on salivary fluid, urine and serum samples by High Resolution Inductively Coupled Plasma-Mass Spectrometry. In addition, the degradation of the dental prostheses was assessed by both a "leaching test" and an analysis of the micro morphology of orthodontic prostheses. The induction of IFN-γ production by Pd was assessed in PBMC by the ELISpot assay. Skin sensitization to Pd was evaluated by patch testing and clinical examination. Ten healthy subjects were comparatively tested as controls. We found a specific induction of an IFN-γ response by Pd in PBMC collected from all the subjects positive to Pd at patch testing. On the contrary, control subjects did not show any response to Pd as assessed by IFN-γ ELISpot assay or by skin testing. Remarkably, the levels of Pd in all biological samples (saliva, sera, urine) were significantly higher in Pd-sensitized patients than in those collected from controls, reaching the highest concentrations in the urine. The leaching studies gave additional evidence that the dental appliances can release measurable levels of Pd in saliva. Oral clinical symptoms in patients with Pd dental prostheses were associated with measurable levels of Pd in the biological fluids, the induction of Pd-specific IFN-γ responses in PBMC and the clinical evidence of skin sensitization to Pd. These data suggest that dental appliances may represent an active source of Pd in the body, and this, in turn, can favour the clinical setting of a hypersensitivity to this metal

    Hepatitis C Virus Infection Among non-IDU HIV-Infected and Uninfected Men who Have Sex with Men

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    In the Mediterranean countries, hepatitis C virus infection affect nearly 45% of HIV-1 infected individuals, consistently to the high proportion of patients with a history of intravenous drug use and exposed to the two viruses by parenteral route. Even in association with HIV-infection, HCV infection is rarely transmitted through sexual intercourse due to the lower efficiency of mucosal exposure to virus than that blood-borne. Thus, the incidence and prevalence of HCV infection are far lower among the non-intravenous drug users (IDU) at risk of sexually transmitted infections (STI). Two hypotheses may be taken in account to explain the lower prevalence rates observed in our seroprevalence study. The MSMs participating to our study could have less sexual contacts with IDU-MSMs than other gay community residents in other western countries. The non-IDU MSMs recruited in this study could have a lower frequency of at-risk sexual practices for HCV then the non-IDU MSMs enrolled in other studies

    Misidentification of Streptococcus uberis as a human pathogen: a case report and literature review.

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    Summary Streptococcus uberis is an environmental bacterium responsible for bovine mastitis. It is occasionally described as a human pathogen, though in most cases the identification was based on biochemical phenotyping techniques. This report shows that the biochemical phenotyping may incorrectly identify Enterococcus faecium as S. uberis
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