Dysenteriae Infection Research Articles

Preliminary Investigations on the Therapeutic Efficacy and Safety of Mixed Probiotic Lactic Acid Bacteria on Albino Rats Challenged with Shigella dysenteriae

This study investigates the potential of lactic acid bacteria (LAB) from the Nigerian beverage “kunun zaki” as alternative therapeutic agents against Shigella dysenteriae infections. In light of rising antibiotic resistance, the decline in probiotic usage prompted interest in LAB’s role in countering bacterial dysentery. Shigella dysenteriae, a significant cause of dysentery in developing nations, prompted this research which aims to carry out a preliminary investigation on the therapeutic efficacy and safety of mixed probiotic lactic acid bacteria on albino rats challenged with Shigella dysenteriae. Lactic acid bacteria, known for treating infections, were isolated from the beverage and tested against Shigella dysenteriae. The study employed 15 albino rats for in vivo trials, inducing diarrhea and treating with Lactococcus lactis and Lactobacillus brevis separately (T1 and T2) and combined in a 1 : 1 ratio (T3). Clinical parameters were observed before and after treatment. This revealed that L. lactis and L. brevis administration lowered rectal temperature from an average of 42°C caused by infection to 36.5°C. Stool consistency improved from light brown loose to dark brown semisolid, signifying reduced diarrhea. Bacteriological analysis displayed significant reduction ( p < 0.05 ) in Shigella counts in rat intestines across all treatments— 220 ± 2.88 C F U / g to 19.00 ± 1.77 C F U / g , 8.33 ± 0.88 C F U / g , and 65.00 ± 2.88 C F U / g for T1, T2, and T3, respectively. The mixed LAB treatment was notably effective. Lactic acid bacteria counts increased significantly in Shigella-treated rats versus the positive control. Hematology and liver function parameters showed no significant differences between treatments and untreated controls. Lactic acid bacteria from “kunun zaki” exhibited curative potential, individually or combined, against Shigella dysenteriae. These lactic acid bacteria also positively influenced gut microbiota in Shigella-infected albino rats.

Effect of Chestnut (Castanea Mollissima Blume) Bur Polyphenol Extract on Shigella dysenteriae: Antibacterial Activity and the Mechanism.

Shigella dysenteriae is a highly pathogenic microorganism that can cause human bacillary dysentery by contaminating food and drinking water. This study investigated the antibacterial activity of chestnut bur polyphenol extract (CBPE) on S. dysenteriae and the underlying mechanism. The results showed that the minimum inhibitory concentration (MIC) of CBPE for S. dysenteriae was 0.4 mg/mL, and the minimum bactericidal concentration (MBC) was 1.6 mg/mL. CBPE treatment irreversibly disrupted cell morphology, decreased cell activity, and increased cell membrane permeability, cell membrane depolarization, and cell content leakage of S. dysenteriae, indicating that CBPE has obvious destructive effects on the cell membrane and cell wall of S. dysenteriae. Combined transcriptomic and metabolomics analysis revealed that CBPE inhibits S. dysenteriae by interfering with ABC protein transport, sulfur metabolism, purine metabolism, amino acid metabolism, glycerophospholipid metabolism, and some other pathways. These findings provide a theoretical basis for the prevention and treatment of S. dysenteriae infection with extract from chestnut burs.

Epidemiology of Dysentery, Uganda, 2014-2018

Introduction: Shigella dysenteriae infection (dysentery) is endemic in developing countries. In Uganda, dysentery is a priority disease for surveillance, however, there is a paucity of data on its magnitude and distribution. We used surveillance data to describe dysentery cases in Uganda, 2014-2018.

Evaluation of the Anti-Shigellosis Activity of Dietary Isothiocyanates in Galleria mellonella Larvae.

Cruciferous vegetables, widely present in daily diets, are a rich source of organosulfur compounds with proven health benefits, especially chemopreventive or antioxidative effects. Isothiocyanate derivatives (ITCs) exhibit a broad spectrum of biological and pharmacological activity and recently, their antibacterial properties have been of particular importance. Here, we have focused on the anti-shigellosis activity of sulforaphane (SFN) and phenethyl ITC (PEITC). The genus Shigella causes gastroenteritis in humans, which constitutes a threat to public health. Production of a potent Stx toxin by S. dysenteriae type 1 results not only in more severe symptoms but also in serious sequela, including the hemolytic uremic syndrome. Here, we present evidence that two aliphatic and aromatic ITCs derivatives, SFN and PEITC, have an effective antibacterial potency against S. dysenteriae, also negatively regulating the stx gene expression. The molecular mechanism of this effect involves induction of the global stress-induced stringent response. ITCs also inhibit bacterial virulence against the Vero and HeLa cells. We present evidence for the therapeutic effect of sulforaphane and phenethyl ITC against a S. dysenteriae infection in the Galleria mellonella larvae model. Thus, our results indicate that isothiocyanates can be effectively used to combat dangerous bacterial infections.

Phage Therapy in Bacterial Infection

Phage therapy has proven to be an effective method to control bacterial infection [1] and it has been successfully applied for the treatment of Shigella dysenteriae infections in children. The phage therapy approach is an effective method for controlling multidrug-resistant bacteria. Félix d’Herelle discovered phages as a lytic agent active on dysentery bacteria exactly 100 years ago [2]. When working on cholera in India, d’Herelle observed that mortality declines during an epidemic.

Isolation and Characterization of a Novel myovirus Infecting Shigella dysenteriae from the Aeration Tank Water.

The genome sequence, morphology, and genetic features of a novel phage, named SSE1, is reported here. Phage SSE1 that infects Shigella dysenteriae (China General Microbiological Culture Collection Center number: 1.1869) was isolated from the aeration tank water of a sewage treatment plant. SSE1 showed morphological features associated with those of phages in Myoviridae. The whole genome sequence of phage SSE1 is composed of 169,744bp with the GC content of 37.51%. The double-stranded DNA of SSE1 contains 270 open reading frameworks (ORFs). Phylogenetically, phage SSE1 showed a stronger homology (whole genome and terminase large subunit protein sequence) to Escherichia phages than other Shigella phages in the NCBI database, but SSE1 did not infect Escherichia stains. This indicates that phage SSE1 should be a novel phage infecting Shigella dysenteriae. Besides, the result of this study provided a new idea for phage therapy. SSE1 may become a candidate for potential therapy against Shigella dysenteriae infection in clinical applications.

Therapeutic Potency of Mangosteen (Garcinia mangostana) Peel Extract For Shigella dysenteriae Infected Mice’s Colon Mucosal Destruction

Introduction : Antibiotics treatment for bacillary dysentery due to Shigella dysenteriae infection have shown resistancy. Mangosteen (Garcinia maangostana) peel have a therapy potency for Shigella dysenteriae infection due to its antibacterial and antiinflamation activity.Methods : This research was an experimental research, 30 mice was used which divided to 5 groups. The mice was infected with Shigella dysenteriae intraperitoneally, then azithromycin, aquadest, and 3 different doses of mangosteen (Garcinia mangostana) peel was given for each group for 5 days, which then the mice’s colon was collected and made into histopathology slide and its mucosal destruction was observed in 3 fields of view in each slide, 1 – 4 score was given acording to its mucosal destruction. Kruskal-Wallis test is used to analyze the data and then Mann Whitney test also used for further analysis.Result : there was a healing effect obeserved when mangosteen (Garcinia mangostana) peel extract was given to the mice’s colon mucosal, 100 mg/Kg body mass dose of mangosteen (Garcinia mangostana) peel extract already given a positive effect on mice’s mucosal colon histopathological appearance, no difference observed between 3 dose given.Conclusion : Mangosteen (Garcinia mangostana) peel extract consumption gave healing appearance to destruction of colon mucosal wall of mice with Shigella dysenteriae infection at 100 mg/Kg body mass.

Remediation of intramacrophageal Shigella dysenteriae type 1 by probiotic lactobacilli isolated from human infants' stool samples.

Background & objectives:Shigella dysenteriae is one of the most virulent pathogens causing bacillary dysentery and is responsible for high mortality in infants. To reduce the load of antibiotic therapy for treating shigellosis, this study was carried out to assess the ex vivo effect of novel probiotic lactobacilli, isolated from infant's stool samples, on killing S. dysenteriae type 1 residing in the rat macrophages.Methods:Stool samples from infants were collected, processed for the isolation of lactobacilli and screened for the probiotic attributes (acid tolerance, bile tolerance, ability to adhere intestinal cells and anti-S. dysenteriae activity). The effect of cell-free supernatant of lactobacilli on Shigella- infected macrophages in terms of phagocytic ability, extent of lipid peroxidation, nitrite, superoxide dismutase and glutathione levels was evaluated.Results:Based on the probiotic attributes, three lactobacilli were isolated from the stool samples of infants. Using classical and molecular tools, these isolates were identified as Lactobacillus pentosus, L. Paraplantarum and L. rhamnosus. All the three lactobacilli had the ability to kill intramacrophage S. dysentriae type 1. The anti-Shigella activity of the probiotic lactobacilli was attributed to increased antioxidative ability and decreased free radical production by the infected macrophages.Interpretation & conclusions:Probiotic cocktail of L. pentosus, L. paraplantarum and L. rhamnosus showed ex vivo killing of S. dysenteriae residing inside the rat macrophages significantly. This cocktail has the potential to be used as a natural alternative for treating S. dysenteriae infection, especially in infants, however, further studies need to be done to confirm these finding in vivo.

Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate β-catenin degradation which in turn decreased the association between NF-κB and β-catenin. Also, we showed that S.dysenteriae infection increased GSK-3β kinase activity which in turn phosphorylates β-catenin for its degradation by ubiquitination and upregulates IL-8 through NF-κB activation thereby leading to inflammation. Thus these findings revealed the role of β-catenin/ NF-κB and GSK-3β in modulating the inflammatory response during bacterial infection and also showed that β-catenin acts as a critical regulator of inflammation.

Aloe vera (Aloe barbadensis Miller) supplemented probiotic lassi prevents Shigella infiltration from epithelial barrier into systemic blood flow in mice model.

The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid. Blood was collected in heparinized tubes for various haematological studies. Oral administration of APL showed a significant (p<0.05) reduction in the Shigella counts (log cfu/mL) in all organs as compared to other treatment groups at different intervals after post feeding. Similarly, secretary IgA antibody levels (μg/mL) in intestinal fluid were significantly (p<0.05) increased in case of APL fed mice. Further, feeding of APL also demonstrated a positive effect on different haematological parameters viz. Hb (gm %), RBC and WBC count. The results indicated the immunoprotective effects of APL against Shigella dysenteriae induced infection in mice.

Shigella dysenteriae modulates BMP pathway to induce mucin gene expression in vivo and in vitro.

Mucosal epithelial cells in the intestine act as the first line of host defense against pathogens by increasing mucin production for clearance. Despite this fact, the underlying molecular mechanisms by which Shigella dysenteriae transduce mucin gene expression remain poorly defined. The goal of this study was to determine the role of Bone morphogenetic protein (BMP) pathway in mucin gene expression during S. dysenteriae infection. In this study we demonstrate that S. dysenteriae activates BMP signaling to induce MUC2 and MUC5AC gene expression in rat ileal loop model and in vitro. We also observed that BMP pathway regulates CDX2 expression which plays a critical role in induction of MUC2 gene during S. dysenteriae infection. In SMAD4 silenced cells S. dysenteriae infection did not abrogate MUC2 and MUC5AC gene expression whereas in CDX2 silenced cells it induces differential expression of MUC5AC gene. These results suggest that SMAD4-CDX2 induces MUC2 gene expression whereas SMAD4 directly influences differential expression of MUC5AC gene. Altogether, our results show that during S. dysenteriae infection the BMP pathway modulates inflammatory transcription factors CDX2 and SMAD4 to induce MUC2 and MUC5AC gene expression which plays a key role in the regulation of host mucosal defense thereby paving a cue for therapeutic application.

Survival of Salmonella Typhi and Shigella dysenteriae in Dehydrated Infant Formula

Powdered infant formula has previously been linked to the transmission of various bacterial pathogens in infants resulting in life-threatening disease and death. Survival studies of 2 common foodborne pathogens, Salmonella enterica serovar Typhi and Shigella dysenteriae, in powdered infant formula have not been previously studied despite the potentially devastating consequences from ingestion of these organisms, particularly by newborns, in case of a natural or deliberate contamination event. Therefore, to better predict the risk of S. Typhi and S. dysenteriae infection from consumption of infant formula, the present study was undertaken to determine survival of these microorganisms in dry infant formula under varying atmospheric conditions. A 2-strain cocktail of S. Typhi and a 3-strain cocktail of S. dysenteriae were stored for up to 12 wk in dehydrated infant formula in an ambient air or nitrogen atmosphere. Viable counts of S. Typhi at 12 wk in infant formula revealed a 2.9- and 1.69-log decrease in ambient air and nitrogen atmosphere, respectively. Viable counts of S. dysenteriae at 12 wk in infant formula revealed a 0.81- and 0.42-log decrease in ambient air and nitrogen atmosphere, respectively. These results show that S. Typhi and S. dysenteriae can remain viable for prolonged periods of time in powdered infant formula, and the presence of nitrogen enhances survival. Our goal in this work was to study the survival of S. Typhi and S. dysenteriae in dehydrated storage conditions in infant formula. This interest is partially generated by the possibility of using these 2 microorganisms to deliberately contaminate the food supply. The outcome of this study will help us to have a better idea how to respond and react to the risk of deliberate food contamination.

Isolation and partial characterisation of a novel lectin from Aegle marmelos fruit and its effect on adherence and invasion of Shigellae to HT29 cells.

Lectins are a class of ubiquitous proteins/glycoproteins that are abundantly found in nature. Lectins have unique carbohydrate binding property and hence have been exploited as drugs against various infectious diseases. We have isolated one such novel lectin from the fruit pulp of Aegle marmelos. The isolated lectin was partially characterised and its effect against Shigella dysenteriae infection was evaluated. The isolated lectin was found to be a dimeric protein with N-acetylgalactosamine, mannose and sialic acid binding specificity. The effect of Aegle marmelos fruit lectin on the adherence of Shigella dysenteriae to human colonic epithelial cells (HT29 cells) was evaluated by Enzyme Linked Immune Sorbent Assay and invasion was analysed. The protective nature of the Aegle marmelos fruit lectin was assessed by analyzing apoptosis through dual staining method. Aegle marmelos fruit lectin significantly inhibited hemagglutination activity of Shigella and its minimum inhibitory concentration is 0.625 µg/well. Further, at this concentration lectin inhibited Shigella dysenteriae adherence and invasion of HT29 cells and protects the HT29 cells from Shigella dysenteriae induced apoptosis. To conclude, isolated lectin dimeric protein with N-acetylgalactosamine, Mannose and sialic acid binding specificity and inhibits adherence and invasion of Shigellae to HT29 cells thus, protects the host.

Hemolytic Uremic Syndrome

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute renal failure. The most frequent form is associated with infections by Shiga-like toxin-producing bacteria (STEC-HUS). Rarer cases are triggered by neuraminidase-producing Streptococcus pneumoniae (pneumococcal-HUS). The designation of aHUS is used to refer to those cases in which an infection by Shiga-like toxin-producing bacteria or S. pneumoniae can be excluded. Studies performed in the last two decades have documented that hyperactivation of the complement system is the pathogenetic effector mechanism leading to the endothelial damage and the microvascular thrombosis in aHUS. Recent data suggested the involvement of the complement system in the pathogenesis of STEC-HUS and pneumococcal-HUS as well. Clinical signs and symptoms may overlap among the different forms of HUS; however, pneumococcal-HUS and aHUS have a worse prognosis compared with STEC-HUS. Early diagnosis and identification of underlying pathogenetic mechanism allows instating specific support measures and therapies. In clinical trials in patients with aHUS, complement inhibition by eculizumab administration leads to a rapid and sustained normalization of hematological parameters with improvement in long-term renal function. This review summarizes current concepts about the epidemiological findings, the pathological and clinical aspects of STEC-HUS, pneumococcal-HUS, and aHUS, and their diagnosis and management.

Role of anti-CD3 in modulation of Th1-type immune response in Shigella dysenteriae infection

A murine model was used to evaluate the role of anti-CD3 in modulating a Th1-type response by restimulation of T-cells after immunization with the 57 kDa immunodominant antigen of Shigella dysenteriae 1 outer-membrane proteins (OMPs), followed by Shigella infection after immunization. To observe the effect of anti-CD3, other T-cell cultures were also established following anti-CD1, anti-IL2 and phytohaemagglutinin stimulation. Anti-CD3 stimulation of reconstituted T-cells showed 'mean' levels of CD4 and CD25 were enhanced by 34.5 and 31.1 % in immunized mice, which was comparable to 53.2 and 50.7 %, respectively, in challenged-immunized mice, and were dominant over CD8+ T-cells. Levels of IL2 generated by anti-CD3-stimulated T-cells of immunized mice were greater than those of unstimulated T-cells and were significantly elevated in challenged-immunized mice. The reactivity of T-cells indicated their complete responsiveness, as anti-CD3 antibody might not inhibit the migration of the macrophages but rather inhibit IL4. These macrophage factors synergistically act with anions towards an activated response, which in turn provokes IL2 secretion with a low degree of internalization of its receptor. Thus, sharing of IL2 to form a high-affinity receptor complex with CD4+ T-cells through motive signals suggested a generalized T-cell activation with increased humoral responses. Macrophage migration inhibition factor (MIF) and IL4 responses during anti-CD3 stimulation of immunized mice indicated that the role of anti-CD3 in generation of O2- is due to a synergistic effect by Th1 subsets of Th0 cells. The above findings should have implications for understanding the immunoregulatory role of anti-CD3 associated with 57 kDa antigen in immunoprophylactic measures.

Bidirectional concentration-dependent effects of tumor necrosis factor alpha in Shigella dysenteriae-related seizures.

We have previously demonstrated that pretreatment of mice with Shigella dysenteriae sonicate enhanced their susceptibility to pentylenetetrazole-induced seizures and that tumor necrosis factor alpha (TNF-alpha) was proconvulsive in this respect. The present study shows that TNF-alpha, at high concentrations, may also exert a suppressive effect on Shigella-mediated seizures. This implies that high levels of TNF-alpha may play a protective role in neurologic complications of S. dysenteriae infection.

Enzyme-linked immunosorbent assay for shigella toxin.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of shigella toxin. For the assay, a mouse monoclonal antibody against the B subunit of the toxin and a rabbit polyclonal antibody against the holotoxin were employed. The monoclonal antibody was used to coat wells of a microtiter plate, and the polyclonal antibody preparation was used as the detecting antibody. The amount of bound polyclonal antibody was determined by using a goat anti-rabbit immunoglobulin G-alkaline phosphatase conjugate and substrate. The ELISA was able to detect as little as 12 pg (0.06 ng/ml) of shigella toxin. The assay was specific for shigella toxin, not detecting a variety of other bacterial enterotoxins and lethal toxins. The ELISA values correlated well with cytotoxin activity during toxin purification. Shigella toxin was detected by ELISA and by immunoblot analysis in human fecal specimens from persons with S. dysenteriae infections, demonstrating that this toxin is produced in vivo.

Rectal Histology in Acute Bacillary Dysentery

A recent epidemic of acute Shigella dysentery in West Bengal (India) provided us with an opportunity to examine the rectal mucosal abnormalities seen in this condition. One hundred two patients were investigated using sigmoidoscopy, rectal biopsy, and rectal swab for culture. Pure culture of Shigella was obtained in 37 cases, and the rectal biopsy specimens from these patients were assessed in detail. The mean (+/- SD) duration of illness was 47.8 +/- 27.4 h (range 8-120 h), and most patients (31 of 37, 84%) had diarrhea with blood and mucus in the stools. Significant findings at histology were as follows. (a) Cellular infiltrate was predominantly round cell or mixed round cell and neutrophilic in the majority of patients (27, 73%). (b) Disorganization of crypts was seen in as many as 31 patients (84%); in most subjects the distorted architecture was mild, but in a few the defect was severe with crypt branching and dilatation. (c) In the majority of patients the inflammatory process extended to the muscularis mucosae and submucosa; edema with or without increased cellular infiltrate was seen in the muscularis mucosae in 92% and in the submucosa in 80%. (d) There was no difference in the rectal histology of patients with a short history of disease (less than 48 h) compared with those with a longer history, except for goblet cell depletion which was more in those with diarrhea for more than 48 h. (e) The mucosal abnormalities in patients with watery diarrhea were, in general, milder than in those with dysentery, although the difference was statistically not significant; 2 of 6 patients with watery diarrhea had severe colitis. (f) The mucosal abnormalities were more severe in patients with Shigella dysenteriae infection compared with Shigella flexneri.

Shigella infections in the United States, 1974-1980.

During the seven-year period 1974-1980, 93,516 Shigella isolates from humans were reported to the Centers for Disease Control, Atlanta, through a nationwide surveillance system. Over the past 30 years, the reported incidence of shigellosis has been declining in contrast to that reported for salmonellosis. Shigella sonnei (group D) now accounts for approximately 70% of the Shigella isolates reported, since most of the decline has been due to the increasingly less frequent infections caused by Shigella flexneri (group B); Shigella dysenteriae infections are now uncommon. The highest reported rates of shigellosis are from the western states and among children from one to five years of age. Among the total population of the United States, the ratio of S. flexneri to S. sonnei isolates was 0.28 among persons from one to 19 years of age and 0.45 among persons greater than or equal to 20 years of age; among American Indians the proportion of S. flexneri was much greater, the corresponding ratios being 2.1 and 2.9, respectively; in both groups the ratios for children younger than one year of age resembled those obtaining for adults. Age-related acquisition of immunity to S. sonnei may explain these observations.

Studies with Shigella dysenteriae (Shiga) infection and intoxication in Macacus mulatta monkeys.

Infections with Shigella paradysenteriae (Flexner) occur spontaneously in monkeys, and epidemics within a colony are not uncommon. Infections with Shigella dysenteriae (Shiga) have not been described in these animals. Whether or not it is possible to produce S. dysenteriae infection in monkeys is a question of more than academic interest. The study of the clinical and pathological picture produced in monkeys by S. dysenteriae (Shiga) and its toxins might give useful information about this relatively rare type of dysentery and afford an opportunity to study its treatment and prevention as well. The possibility of producing infection or intoxication of monkeys with S. dysenteriae (Shiga) or toxins prepared from this organism was investigated in this study, and the results are herein reported.