European Journal of Microbiology & Immunology最新文献

Due to the increasing application of antibiotics not only in healthcare settings but also in conventional agriculture and farming, multidrug-resistant (MDR) bacterial pathogens are rising worldwide. Given the increasing prevalence of infections caused by MDR bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE pathogen complex), it is pivotal to explore novel alternative or adjunct treatment options such as phytochemicals with antibiotic properties. Vanillin and vanillin acid represent biologically active ingredients in vanilla that has been known for long for its health-beneficial including antimicrobial effects besides its role as flavoring agent. Therefore, we performed a literature search from the past 10 years summarizing the knowledge regarding the effects of vanilla constituents against bacterial including MDR pathogens. Our survey revealed that vanillin and vanillic acid exerted potent effects directed against distinct Gram-positive and Gram-negative bacteria by inhibiting growth, viability, biofilm formation, quorum sensing and virulence. Remarkably, when combining vanillin or vanillic acid with defined synthetic antibiotics pronounced synergistic effects directed against distinct pathogenic including ESCAPE strains could be observed. In conclusion, vanilla ingredients constitute promising alternative or adjunct options in the combat of infections caused by MDR bacterial pathogens.

In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.

Intestinal amoebiasis in a 35-year-old German patient with a 3 weeks travel history in Indonesia was initially misidentified as non-steroidal anti-inflammatory-drug associated colitis in colonoscopy and histopathological analysis. Furthermore, initial stool examination by microscopy and Entamoeba faecal antigen ELISA did not reveal any protozoan infection. When cessation of non-steroidal anti-inflammatory drug (NSAID) use and mesalazine treatment did not lead to clinical improvement, the patient presented to a specialist for tropical diseases. An intensive reinvestigation including a workup of formalin-fixed, paraffin-embedded colonic biopsies by molecular analysis with real-time PCR and fluorescence in situ hybridization (FISH) proofed the diagnosis of Entamoeba histolytica colitis. Molecular methods including real-time PCR and FISH for the diagnosis of amoebiasis from histopathological samples are rarely used for the diagnosis of E. histolytica infections. Bloody diarrhoea vanished after the onset of metronidazole treatment. In conclusion, the here-presented case demonstrates how modern molecular diagnostics may help to diagnose E. histolytica-associated colitis, even from difficult specimens like paraffin-embedded, formalin-fixed tissue.

Gut microbiota depletion is a pivotal prerequisite to warrant Campylobacter jejuni infection and induced inflammation in IL-10-/- mice used as acute campylobacteriosis model. We here assessed the impact of an 8-week antibiotic regimen of ampicillin, ciprofloxacin, imipenem, metronidazole, and vancomycin (ABx) as compared to ampicillin plus sulbactam (A/S) on gut microbiota depletion and immunopathological responses upon oral C. jejuni infection. Our obtained results revealed that both antibiotic regimens were comparably effective in depleting the murine gut microbiota facilitating similar pathogenic colonization alongside the gastrointestinal tract following oral infection. Irrespective of the preceding microbiota depletion regimen, mice were similarly compromised by acute C. jejuni induced enterocolitis as indicated by comparable clinical scores and macroscopic as well as microscopic sequelae such as colonic histopathology and apoptosis on day 6 post-infection. Furthermore, innate and adaptive immune cell responses in the large intestines were similar in both infected cohorts, which also held true for intestinal, extra-intestinal and even systemic secretion of pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL-6. In conclusion, gut microbiota depletion in IL-10-/- mice by ampicillin plus sulbactam is sufficient to investigate both, C. jejuni infection and the immunopathological features of acute campylobacteriosis.

Introduction: Bacteremia is responsible for high rates of morbidity and mortality. The increasing prevalence of multidrug-resistant (MDR) bacteria in intensive care units (ICU) is a growing concern. Hence, prior knowledge of bacterial epidemiology and resistance phenotypes is required to optimize these infections' management. The objective of this study was to determine the epidemiological profile of bacteremia in ICU settings, as well as the place occupied by MDR bacteria in these infections.

Methods: It is a prospective study carried out over 10 months on episodes of bacteremia in the ICU of Mohammed V Military Teaching Hospital (Rabat, Morocco). Microorganism growth was detected using fluorescent technology, species identification was based on morphological and biochemical characteristics. Antimicrobial susceptibility testing was performed following the recommendations of the Antibiogram Committee of the French Society of Microbiology (CA-SFM) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

Results: Among 504 hospitalized patients, sixty-one (12.1%) presented at least one episode of bacteremia. Forty patients (65.6% of bacteremic patients) presented at least one episode of bacteremia due to MDR bacteria. Male gender, cardiovascular diseases, diabetes and previous hospitalization were significant risk factors for the acquisition of MDR bacteremia. Isolated bacteria were mainly Gram-negative bacilli (GNB) (n = 62; 68.9%) dominated by Acinetobacter baumannii (n = 19; 21.1%) and Klebsiella pneumoniae (n = 16; 17.8%). MDR bacteria were represented by multi-resistant Acinetobacter baumannii (n = 19; 44.2%), extended-spectrum beta-lactamases-producing Enterobacterales (n = 9; 20.9%) and carbapenem-resistant Enterobacterales (n = 7; 16.3%). Carbapenems (n = 40; 65.6%), Aminoglycosides (n = 32; 52.5%) and Polypeptides (n = 24; 39.3%) were the most used antimicrobials. Mortality rates were 66.6% (n = 40) and 85% (n = 43) in patients with non MDR bacteremia and MDR bacteremia respectively.

Conclusion: Limiting the spread of MDR bacteria and improving the management of bacteremic patients require continuous monitoring of bacteremia as well as adapting the therapeutic and preventive strategy.

Naturally-occurring compounds are acknowledged for their broad antiviral efficacy. Little is however known about their mutual cooperation. Here, we evaluated in vitro efficacy of the defined mixture of agents against the RdRp complex of the original SARS-CoV-2 and Omicron variant. This composition of vitamin C, N-acetylcysteine, resveratrol, theaflavin, curcumin, quercetin, naringenin, baicalin, and broccoli extract showed to inhibit activity of RdRp/nsp7/nsp8 both these variants. In vitro exposure of recombinant RdRp complex to individual compounds of this composition pointed to quercetin as the driving inhibitory compound. The outcome of this study supports the motion of antiviral efficacy of natural compounds against SARS-CoV-2 and Omicron and implies that their reciprocal or mutual interaction may augment antiviral action through simultaneous effect on different mechanisms. Consequently, this makes it more difficult for an infectious agent to evade all these mechanisms at the same time. Considering the urgency in finding effective prevention, but also side-effects free treatment of COVID-19 our results call for clinical affirmation of the benefits of this micronutrient combination in both preventive and therapeutic aspects. Whether observed effects can be achieved, by concentrations of the active agents used in these in vitro experiments, in in vivo or clinical setting warrants further study.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RSCB PDB) provides a wide range of digital data regarding biology and biomedicine. This huge internet resource involves a wide range of important biological data, obtained from experiments around the globe by different scientists. The Worldwide Protein Data Bank (wwPDB) represents a brilliant collection of 3D structure data associated with important and vital biomolecules including nucleic acids (RNAs and DNAs) and proteins. Moreover, this database accumulates knowledge regarding function and evolution of biomacromolecules which supports different disciplines such as biotechnology. 3D structure, functional characteristics and phylogenetic properties of biomacromolecules give a deep understanding of the biomolecules' characteristics. An important advantage of the wwPDB database is the data updating time, which is done every week. This updating process helps users to have the newest data and information for their projects. The data and information in wwPDB can be a great support to have an accurate imagination and illustrations of the biomacromolecules in biotechnology. As demonstrated by the SARS-CoV-2 pandemic, rapidly reliable and accessible biological data for microbiology, immunology, vaccinology, and drug development are critical to address many healthcare-related challenges that are facing humanity. The aim of this paper is to introduce the readers to wwPDB, and to highlight the importance of this database in biotechnology, with the expectation that the number of scientists interested in the utilization of Protein Data Bank's resources will increase substantially in the coming years.

Despite vaccine availability, the global spread of COVID-19 continues, largely facilitated by emerging SARS-CoV-2 mutations. Our earlier research documented that a specific combination of plant-derived compounds can inhibit SARS-CoV-2 binding to its ACE2 receptor and controlling key cellular mechanisms of viral infectivity. In this study, we evaluated the efficacy of a defined mixture of plant extracts and micronutrients against original SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants. The composition containing vitamin C, N-acetylcysteine, resveratrol, theaflavin, curcumin, quercetin, naringenin, baicalin, and broccoli extract demonstrated a highest efficacy by inhibiting the receptor-binding domain (RBD) binding of SARS-CoV-2 to its cellular ACE2 receptor by 90%. In vitro exposure of test pseudo-typed variants to this formula for 1 h before or simultaneously administrated to human pulmonary cells resulted in up to 60% inhibition in their cellular entry. Additionally, this composition significantly inhibited other cellular mechanisms of viral infectivity, including the activity of viral RdRp, furin, and cathepsin L. These findings demonstrate the efficacy of natural compounds against SARS-CoV-2 including its mutated forms through pleiotropic mechanisms. Our results imply that simultaneous inhibition of multiple mechanisms of viral infection of host cells could be an effective strategy to prevent SARS-CoV-2 infection.

Transcription factors of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) family control important signaling pathways in the regulation of the host innate immune system. Various bacterial pathogens in the human gastrointestinal tract induce NF-ĸB activity and provoke pro-inflammatory signaling events in infected epithelial cells. NF-ĸB activation requires the phosphorylation-dependent proteolysis of inhibitor of ĸB (IĸB) molecules including the NF-ĸB precursors through ubiquitin-mediated proteolysis. The canonical NF-ĸB pathway merges on IĸB kinases (IKKs), which are required for signal transduction. Using CRISPR-Cas9 technology, secreted embryonic alkaline phosphatase (SEAP) reporter assays and cytokine enzyme-linked immunosorbent assay (ELISA), we demonstrate that the actin-binding protein cortactin is involved in NF-ĸB activation and subsequent interleukin-8 (IL-8) production upon infection by Helicobacter pylori, Salmonella enterica and Pseudomonas aeruginosa. Our data indicate that cortactin is needed to efficiently activate the c-Sarcoma (Src) kinase, which can positively stimulate NF-ĸB during infection. In contrast, cortactin is not involved in activation of NF-ĸB and IL-8 expression upon infection with Campylobacter species C. jejuni, C. coli or C. consisus, suggesting that Campylobacter species pluralis (spp.) induce a different signaling pathway upstream of cortactin to trigger the innate immune response.

Introduction: Ticks are frequently polyinfected and can thus transmit numerous microorganisms. A large number of bacteria, parasites and viruses are transmitted by tick bites and could cause different signs and symptoms in patients. The main goal of this study was to search for these numerous microorganisms in patients presenting with persistent polymorphic syndrome possibly due to a tick bite (SPPT).

Patients and methods: The following microorganisms were searched for in saliva, urine, venous and capillary blood by using real time PCR: Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Borrelia hermsii, Bartonella spp., Bartonella quintana, Bartonella henselae, Ehrlichia spp., Anaplasma spp., Rickettsia spp., Coxiella burnetii, Brucella spp., Francisella tularensis, Mycoplasma spp., Chlamydia spp., Babesia spp., Theileria spp.

Results: 104 patients were included. 48% of the patients were poly-infected, and 25% harboured at least three different microorganisms. Borrelia spp. were not the most frequent bacteria observed, observed far behind Mycoplasma spp., Rickettsia spp. and Ehrlichia spp. which were the most frequent microorganisms observed. Piroplasms were found in a significant number of patients. The most sensitive matrix was saliva, followed by urine, capillary blood and venous blood.

Conclusion: Our prospective study has shown that patients with SPPT, a syndrome close to fibromyalgia, could harbour several tick borne microorganisms.