Elevated systemic antibodies towards commensal gut microbiota in autoinflammatory condition

Article No. e3172Non peer reviewedPublisher PD

Multidrug-resistance and presence of class 1 integrons in clinical isolates of Salmonella enterica serotype Enteritidis, circulating in Armenia

Abstract. The aim of this work was detection of class 1 integrons and their contribution to the antimicrobial resistance phenotypes in strains of   subspecies enterica serotype Enteritidis. S. Enteritidis strains (n = 29) were isolated from patients with salmonellosis at “Nork” Clinical Hospital of Infectious Diseases, Yerevan, Republic of Armenia. High prevalence of multi-drug resistance (MDR) phenotypes was revealed and isolates with MDR phenotypes which are rare in the S. Enteritidis serotype were observed. Class 1 integrons were detected in 27,6% of isolates, with the prevalence of a variable region of 1000 bp. Occurrence of the MDR phenotype was more frequent in integron-positive isolates compared to integron-negative isolates of S. Enteritidis. Further studies are necessary to reveal the genetic background of MDR phenotypes and to estimate the genetic kinship among the isolates. Our results suggest a rapid and large-scale penetration of antibiotic resistance genes into populations of S. Enteritidis, which complicates infection control. More rigorous regulations should be imposed on antibiotic use, together with a vigilant epidemiological surveillance, to prevent the emergence and spread of MDR S. Enteritidis

Differential induction of total IgE by two Salmonella enterica serotypes

The main goal of this study was to establish how the inflammation caused by infection with two different Salmonella enterica serotypes, S. Typhimurium and S. Enteritidis, may lead to the predisposition to allergy as measured by total IgE level in the blood. Infection by S. Typhimurium did not affect the systemic IgE concentration while in S. Enteritidis-infected patients there was a significant 3.5-fold increase. This effect was especially profound in patients >4 years old, with up to the eight-fold increase above the norm. The degree of dysbiosis in these two infections measured with the comparative counts of cultivated bacteria showed an inverse relationship with the IgE concentration. Earlier we reported the elevated level of IL-17 in patients infected by S. Enteritidis. In the current study a significant correlation was found between the concentrations of IL-17 and IgE suggesting a possible role played by this cytokine in triggering the production of IgE in response to S. Enteritidis infection

Predominant role of host genetics in controlling the composition of gut microbiota

Background: The human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission. Methodology/Principal Findings: A total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier statu

Molecular Epidemiology and Virulence of Non-Typhoidal <i>Salmonella</i> in Armenia

In this work, we analysed human isolates of nontyphoidal Salmonella enterica subsp. enterica (NTS), which were collected from salmonellosis cases in Armenia from 1996 to 2019. This disease became a leading food-borne bacterial infection in the region, with the younger age groups especially affected. The isolates were characterised by serotyping, Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) typing, and whole genome sequencing (WGS). The main serotypes were S. Typhimurium, S. Enteritidis, and S. Arizonae. ERIC-PCR indicated a high degree of clonality among S. Typhimurium strains, which were also multidrug-resistant and produced extended spectrum beta-lactamases. During the study period, the frequency of S. Typhimurium and S. Arizonae isolations decreased, but with the increase in S. Enteritidis and other NTS. A total of 42 NTS isolates were subjected to WGS and explored for virulence-related traits and the corresponding genetic elements. Some virulence and genetic factors were shared by all NTS serotypes, while the main differences were attributed to the serotype-specific diversity of virulence genes, SPIs, virulence plasmids, and phages. The results indicated the variability and dynamics in the epidemiology of salmonellosis and a high virulence potential of human NTS isolates circulating in the region

Comparison of 16S rRNA gene libraries derived from healthy controls and FMF patients in remission and attack.

*<p>p<0.01, comparison of remission vs. control libraries.</p>**<p>p<0.01, comparison of attack vs. control libraries.</p>***<p>p<0.01, comparison of remission vs. attack libraries.</p

Mean numbers of predominant bacteria in fecal samples of FMF patients in both stages of the disease and healthy controls detected by FISH.

<p>Mean count±SD.</p>*<p>Counts 10⁸ cells per gram of fecal specimen.</p>**<p>The percentage relative to the total number of cells determined by Eub338.</p>†<p>p<0.05 as compared to healthy controls.</p>††<p>p<0.01 as compared to healthy controls.</p

Potential Involvement of Salmonella Infection in Autoimmunity

In this work, we investigated the potential effects of nontyphoidal Salmonella infection on autoantibody (AA) formation. The titer and profiles of autoantibodies in the sera of patients with acute salmonellosis due to Salmonella enterica serovar Typhimurium (S. Typhimurium) or Salmonella enterica serovar Enteritidis (S. Enteritidis) infection, as well as in convalescent patients, were determined with indirect immunofluorescence. A significant increase of autoantibodies in acute diseases caused by both serotypes of Salmonella and during post infection by S. Enteritidis was detected. Antibody profile analysis by multivariate statistics revealed that this increase was non-specific and was not dependent on the infectious agent or disease stage. The results obtained suggest that nontyphoidal Salmonella infection contributes to the generation of autoantibodies and may play a role in autoimmune disease

Distribution of main bacterial groups in respect to colchicine treatment.

<p>Mean count±SD.</p>*<p>Counts 10⁸ cells per gram of fecal specimen.</p>**<p>The percentage relative to the total number of cells determined by Eub338.</p