Authors:Markus M. Heimesaat, Dennis Weschka, Sigri Kløve, Claudia Genger, Nina Biesemeier, Soraya Mousavi, and Stefan Bereswill
Non-antibiotic feed additives including competitive exclusion products have been shown effective in reducing pathogen loads including multi-drug resistant strains from the vertebrate gut. In the present study we surveyed the intestinal bacterial colonization properties, potential macroscopic and microscopic inflammatory sequelae and immune responses upon peroral application of the commercial competitive exclusion product Aviguard® to wildtype mice in which the gut microbiota had been depleted by antibiotic pre-treatment. Until four weeks following Aviguard® challenge, bacterial strains abundant in the probiotic suspension stably established within the murine intestines. Aviguard® application did neither induce any clinical signs nor gross macroscopic intestinal inflammatory sequelae, which also held true when assessing apoptotic and proliferative cell responses in colonic epithelia until day 28 post-challenge. Whereas numbers of colonic innate immune cell subsets such as macrophages and monocytes remained unaffected, peroral Aviguard® application to microbiota depleted mice was accompanied by decreases in colonic mucosal counts of adaptive immune cells such as T and B lymphocytes. In conclusion, peroral Aviguard® application results i.) in effective intestinal colonization within microbiota depleted mice, ii.) neither in macroscopic nor in microscopic inflammatory sequelae and iii.) in lower colonic mucosal T and B cell responses.
Authors:Edna Madai Méndez-Hernández, Jesús Hernández-Tinoco, José Manuel Salas-Pacheco, Luis Francisco Sánchez-Anguiano, Oscar Arias-Carrión, Ada Agustina Sandoval-Carrillo, Francisco Xavier Castellanos-Juárez, Luis Ángel Ruano-Calderón, and Cosme Alvarado-Esquivel
The link between Toxoplasma gondii infection and multiple sclerosis remains controversial. In the present study, we aimed to determine the association between T. gondii seropositivity and multiple sclerosis. Using an age- and gender-matched case-control study, we studied 45 patients who had multiple sclerosis attended in two public hospitals and 225 control subjects without this disease and other neurological disorders in Durango City, Mexico. Serum samples of cases and controls were analyzed for detection of anti-Toxoplasma IgG using a commercially available enzyme-linked immunoassay. One (2.22%) of the 45 patients with multiple sclerosis, and 15 (6.67%) of the 225 control subjects without this disease were seropositive for anti-T. gondii IgG antibodies. No statistically significant difference (OR = 0.31; 95% CI: 0.04–2.47; P = 0.48) in seroprevalence of anti-T. gondii IgG antibodies between cases and controls was found. The frequency of T. gondii seropositivity did not vary among cases and controls about sex or age groups. Results of this study do not support an association between seropositivity to T. gondii and multiple sclerosis. However, additional research with larger sample sizes to confirm this lack of association should be conducted.
Authors:Mangge Zou, Juhao Yang, Carolin Wiechers, and Jochen Huehn
Listeria monocytogenes (Lm) is a food-borne pathogen with a high chance of infecting neonates, pregnant women, elderly and immunocompromised individuals. Lm infection in neonates can cause neonatal meningitis and sepsis with a high risk of severe neurological and developmental sequelae and high mortality rates. However, whether an acute neonatal Lm infection causes long-term effects on the immune system persisting until adulthood has not been fully elucidated. Here, we established a neonatal Lm infection model and monitored the composition of major immune cell subsets at defined time points post infection (p.i.) in secondary lymphoid organs and the intestine. Twelve weeks p.i., the CD8+ T cell population was decreased in colon and mesenteric lymph nodes (mLNs) with an opposing increase in the spleen. In the colon, we observed an accumulation of CD4+ and CD8+ effector/memory T cells with an increase of T-bet+ T helper 1 (Th1) cells. In addition, 12 weeks p.i. an altered composition of innate lymphoid cell (ILC) and dendritic cell (DC) subsets was still observed in colon and mLNs, respectively. Together, these findings highlight organ-specific long-term consequences of an acute neonatal Lm infection on both the adaptive and innate immune system.
Authors:Edit Urbán, Márió Gajdács, and Attila Torkos
Chronic sinusitis caused by anaerobes is a particular concern clinically, because many of the complications are associated with infections caused by these organisms. The aim of this study was to evaluate the incidence of anaerobic bacteria in chronic sinusitis in adults as a part of a prospective microbiological study.
Materials and methods
Over a one-year period, aspirations of maxillary sinus secretions and/or ethmoid cavities were derived in n = 79 adult patients with chronic sinusitis by endoscopy in a tertiary-care teaching hospital in Hungary. The qualitative and quantitative compositions of the total cultivable aerobic and anaerobic bacterial and fungal flora cultured on the samples were compared. Correct anaerobic species level identifications were carried out according to standard methods.
Bacteria were recovered for all of the 79 aspirates and the numbers of the significant cultured isolates (with colony forming units ≥103) were between 1 and 10. A total of 206 isolates, 106 anaerobic and 100 aerobic or facultative-anaerobic strains were isolated. The most common aerobic bacteria were Streptococcus pneumoniae (n = 40), Haemophilus influenzae (n = 29), Moraxella catarrhalis (n = 6), Staphylococcus aureus (n = 7) and Streptococcus pyogenes (n = 6). The anaerobic bacteria included black-pigmented Prevotella spp. and Porphyromonas spp. (n = 27), Actinomyces spp. (n = 13), Gram-positive anaerobic cocci (n = 16), Fusobacterium spp. (n = 19) and Cutibacterium acnes (n = 8).
This study illustrates the microbial dynamics in which anaerobic and aerobic bacteria prevail and highlights the importance of obtaining cultures from patients with chronic sinusitis for guidance in selection of proper antimicrobial therapy.
Obligate anaerobic bacteria are considered important constituents of the microbiota of humans; in addition, they are also important etiological agents in some focal or invasive infections and bacteremia with a high level of mortality. Conflicting data have accumulated over the last decades regarding the extent in which these pathogens play an intrinsic role in bloodstream infections. Clinical characteristics of anaerobic bloodstream infections do not differ from bacteremia caused by other pathogens, but due to their longer generation time and rigorous growth requirements, it usually takes longer to establish the etiological diagnosis. The introduction of matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) has represented a technological revolution in microbiological diagnostics, which has allowed for the fast, accurate and reliable identification of anaerobic bacteria at a low sample cost. The purpose of this review article is to summarize the currently available literature data on the prevalence of anaerobic bacteremia in adults for physicians and clinical microbiologists and to shed some light on the complexity of this topic nowadays.
Authors:Ernst-Jürgen Finke, Wolfgang Beyer, Ulrike Loderstädt, and Hagen Frickmann
Anthrax is an infectious disease of relevance for military forces. Although spores of Bacillus anthracis obiquitously occur in soil, reports on soil-borne transmission to humans are scarce. In this narrative review, the potential of soil-borne transmission of anthrax to humans is discussed based on pathogen-specific characteristics and reports on anthrax in the course of several centuries of warfare. In theory, anthrax foci can pose a potential risk of infection to animals and humans if sufficient amounts of virulent spores are present in the soil even after an extended period of time. In praxis, however, transmissions are usually due to contacts with animal products and reported events of soil-based transmissions are scarce. In the history of warfare, even in the trenches of World War I, reported anthrax cases due to soil-contaminated wounds are virtually absent. Both the perspectives and the experience of the Western hemisphere and of former Soviet Republics are presented. Based on the accessible data as provided in the review, the transmission risk of anthrax by infections of wounds due to spore-contaminated soil is considered as very low under the most circumstance. Active historic anthrax foci may, however, still pose a risk to the health of deployed soldiers.
Authors:Claudia Genger, Sigri Kløve, Soraya Mousavi, Stefan Bereswill, and Markus M. Heimesaat
The physiological colonization resistance exerted by the murine gut microbiota prevents conventional mice from Campylobacter jejuni infection. In the present study we addressed whether this also held true for Campylobacter coli. Following peroral application, C. coli as opposed to C. jejuni could stably establish within the gastrointestinal tract of conventionally colonized mice until 3 weeks post-challenge. Neither before nor after either Campylobacter application any changes in the gut microbiota composition could be observed. C. coli, but not C. jejuni challenge was associated with pronounced regenerative, but not apoptotic responses in colonic epithelia. At day 21 following C. coli versus C. jejuni application mice exhibited higher numbers of adaptive immune cells including T-lymphocytes and regulatory T-cells in the colonic mucosa and lamina propria that were accompanied by higher large intestinal interferon-γ (IFN-γ) concentrations in the former versus the latter but comparable to naive levels. Campylobacter application resulted in decreased splenic IFN-γ, tumor necrosis factor-α (TNF-α), and IL-6 concentrations, whereas IL-12p70 secretion was increased in the spleens at day 21 following C. coli application only. In either Campylobacter cohort decreased IL-10 concentrations could be measured in splenic and serum samples. In conclusion, the commensal gut microbiota prevents mice from C. jejuni, but not C. coli infection.
Stenotrophomonas maltophilia is an aerobic, oxidase-negative and catalase-positive bacillus. S. maltophilia is a recognized opportunistic pathogen. Due to the advancements in invasive medical procedures, organ transplantation and chemotherapy of malignant illnesses, the relevance of this pathogen increased significantly. The therapy of S. maltophilia infections is challenging, as these bacteria show intrinsic resistance to multiple classes of antibiotics, the first-choice drug is sulfamethoxazole/trimethoprim. Our aim was to assess the epidemiology of S. maltophilia from various clinical samples and the characterization of resistance-levels and resistotyping of these samples over a long surveillance period. The study included S. maltophilia bacterial isolates from blood culture samples, respiratory samples and urine samples and the data for the samples, received between January 2008 until December 2017, a total of 817 S. maltophilia isolates were identified (respiratory samples n = 579, 70.9%, blood culture samples n = 175, 21.4% and urine samples n = 63, 7.7%). Levofloxacin and colistin-susceptibility rates were the highest (92.2%; n = 753), followed by tigecycline (90.5%, n = 739), the first-line agent sulfamethoxazole/trimethoprim (87.4%, n = 714), while phenotypic resistance rate was highest for amikacin (72.5% of isolates were resistant, n = 592). The clinical problem of sulfamethoxazole/trimethoprim-resistance is a complex issue, because there is no guideline available for the therapy of these infections.
Authors:Silke Dubbert, Birgit Klinkert, Michael Schimiczek, Trudy M. Wassenaar, and Rudolf von Bünau
Probiotic Escherichia coli strain Nissle 1917 (EcN) has a long history of safe use. However, the recently discovered presence of a pks locus in its genome presumably producing colibactin has questioned its safety, as colibactin has been implicated in genotoxicity. Here, we assess the genotoxic potential of EcN. Metabolic products were tested in vitro by the Ames test, a mutagenicity assay developed to detect point mutation-inducing activity. Live EcN were tested by an adapted Ames test. Neither the standard nor the adapted Ames test resulted in increased numbers of revertant colonies, indicating that EcN metabolites or viable cells lacked mutagenic activity. The in vivo Mammalian Alkaline Comet Assay (the gold standard for detecting DNA-strand breaks) was used to determine potentially induced DNA-strand breaks in cells of the gastro-intestinal tract of rats orally administered with viable EcN. Bacteria were given at 109–1011 colony forming units (CFU) per animal by oral gavage on 2 consecutive days and daily for a period of 28 days to 5 rats per group. No significant differences compared to negative controls were found. These results demonstrate that EcN does not induce DNA-strand breaks and does not have any detectable genotoxic potential in the test animals.
Authors:Jakob Knorr, Steffen Backert, and Nicole Tegtmeyer
The gastric pathogen Helicobacter pylori colonizes approximately half of the human world population. The bacterium injects the effector protein cytotoxin associated gene A (CagA) via a type-IV secretion system into host epithelial cells, where the protein becomes phosphorylated at specific EPIYA-motifs by cellular kinases. Inside the host cell, CagA can interact with over 25 different proteins in both phosphorylation-dependent and phosphorylation-independent manners, resulting in manipulation of host-cell signaling pathways. During the course of an H. pylori infection, certain host-cell proteins undergo tyrosine dephosphorylation in a CagA-dependent manner, including the actin-binding proteins cortactin and vinculin. A predominant response of intracellular CagA is the binding and activation of tyrosine phosphatase, the human Src-homology-region-2-domain-containing-phosphatase-2 (SHP2). Here, we considered the possibility that activated SHP2 might be responsible for the dephosphorylation of cortactin and vinculin. To investigate this, phosphatase inhibitor studies were performed. Additionally, a complete knockout mutant of SHP2 in AGS cells was created by CRISPR/Cas9 technology, and these cells were infected with H. pylori. However, neither the presence of an inhibitor nor the inactivation of SHP2 prevented the dephosphorylation of cortactin and vinculin upon CagA delivery. Tyrosine dephosphorylation of these proteins is therefore independent of SHP2 and instead must be caused by another, as yet unidentified, protein tyrosine phosphatase.