Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Case Report: Bilateral Intra-Parenchymal Hematomas Caused by Ventricular Flood Complicating Neonatal Salmonella typhi Meningitis

Salmonella meningitis is an uncommon condition in neonates, and when it does occur, it is often linked to serious complications, such as subdural collections and abscesses. We present a case involving a 23-day-old neonate diagnosed with Salmonella meningitis, who developed complications including bilateral intra-parenchymal hematomas with ventricular involvement. The infant showed significant improvement following an extended course of systemic antibiotics and supportive care.

Salmonella typhimurium myopericarditis: A case report and review of literature

BACKGROUND Non-typhoidal salmonella(NTS)is a rare,but well-established cause of myopericarditis.Presenting symptoms may be varied,however often revolve around the dual presentation of both myopericarditis and infectious diarrhoea.Given the rarity of NTS related myopericarditis,we conducted a systematic review of the literature,identifying 41 previously reported cases.CASE SUMMARY We present the case of an otherwise healthy 39-year old male,presenting with chest pain in the setting of documented Salmonella typhimurium infection.After further investigation with echocardiogram and laboratory blood tests,a diagnosis of NTS associated myopericarditis was made,and the patient received antibiotic treatment with an excellent clinical outcome.Overall,myopericarditis is rare in NTS.Although treatment for myopericarditis has not been well established,there are guidelines for the treatment of NTS infection.In our review,we found that the majority of NTS cases has been pericarditis(27/42,64.3%),with an average age of 48.3 years,and 71.4%being male.The average mortality across all cases was 31%.CONCLUSION Myopericarditis is a rare,but potentially serious complication of NTS infection,associated with an increased morbidity and mortality.

Deletions in the pyruvate pathway of Salmonella Typhimurium alter SPI1-mediated gene expression and infectivity

Background： Salmonella enter/ca serovar Typhimurium is a major foodborne pathogen worldwide. S. Typhimurium encodes type III secretion systems via Salmonella pathogenicity islands （SPI）, producing the major effector proteins of virulence. Previously, we identified two genes of Salmonella pyruvate metabolism that were up-regulated during chicken cell infection： pyruvate formate lyase I （pf/B） and b/functional acetaldehyde-CoA/alcohol dehydrogenase （adhE）. We were therefore interested in examining the role these genes may play in the transmission of Salmonella to humans. Methods： Mutant strains of Salmonella with single gene deletions for pflB and adhE were created. Invasion and growth in human HCT-8 intestinal epithelial cells and THP-1 macrophages was examined. Quantitative PCR was performed on 19 SPI-1 genes. Results： In HCT-8 cells, both mutant strains had significantly higher intracellular counts than the wild-type from 4 to 48 h post-infection. Various SPI-1 genes in the mutants were up-regulated over the wild-type as early as 1 h and lasting until 24 h post-infection. In THP-1 cells, no significant difference in internal Salmonella counts was observed; however, SPI-1 genes were largely down-regulated in the mutants during the time-course of infection. We also found five SPI-1 genes - hilA, hiIC hill）, sicP and rtsA - which were up-regulated in at least one of the mutant strains in log-phase broth cultures alone. We have therefore identified a set of SPI-1 virulence genes whose regulation is effected by the central metabolism of Salmonella.

Antisalmonellal and antioxidant potential of hydroethanolic extract of Canarium schweinfurthii Engl.(Burseraceae) in Salmonella enterica serovar Typhimurium-infected chicks

Objective:To evaluate the anti-infectious and antioxidant activities of hydroethanolic extract of Canarium schweinfurthii on broiler chickens infected by Salmonella enterica serovar Typhimurium,known to be threatening public health.Methods:Animals were divided into six groups of eight animals per group:the normal control group,negative control group,positive control group and three test groups receiving the plant extract at 5,19 and 75 mg/kg bw,respecively.The evolution of the disease as well as the effectiveness of the treatment were monitored by stool culture from the second day post infection until the end of the treatment.In addition,the effects of treatment on growth performances and feed conversion efficiency of broilers were evaluated.For the assessment of antioxidant status,enzymatic and non-enzymatic biomarkers such as catalase,glutathione peroxidase,malondialdehyde and nitric oxide were evaluated in the serum and tissues of animals.Results:The infected chickens treated with oxytetracycline recovered on day 7 after treatment,while animals treated with 19 and 75 mg/kg of Canarium schweinfurthii extract recovered on day 9 and those with 5 mg/kg of the extract on day 10.Salmonella infection caused a decrease on catalase and glutathione peroxidase activities;the administration of various doses of Canarium schweinfurthii extract increased these enzymatic activities.Animals receiving the extract at 5 mg/kg showed a significant increase in catalase activity in serum,heart and lungs while all concentrations of the extract significantly increased glutathione peroxidase activity in the serum,liver and spleen.Concerning non-enzymatic biomarkers,Salmonella infection caused a significant increase of nitric oxide and malondialdehyde concentration in the liver and lungs.Treatment with 75 mg/kg of the extract significantly reduced nitric oxide concentration in the heart and lungs while each dose of the extract reduced and normalized the malondialdehyde level in the serum.Additionally,malondialdehyde production was significantly decreased in the liver,heart and lungs after administration of Canarium schweinfurthii extract at all doses.Conclusions:The hydroethanolic extract of Canarium schweinfurthii attenuates oxidative stress,and is effective in the treatment of avian salmonellosis.

Salmonella typhi and gallbladder cancer:report from an endemic region

BACKGROUND:Evidence exists of a link between chronic infection by Salmonella typhi(S.typhi) and the development of gallbladder cancer(GBC),but several studies from endemic regions contradict its role in the etiopathogenesis of GBC.This study used various tools to assess the prevalence of S.typhi in patients with GBC and gallstone disease(GSD) in this region with a high incidence of GBC.METHODS:S.typhi was detected in tissue and bile by PCR and culture and in serum by the Widal test and indirect hemagglutination assay(IHA).PCR with two pairs of S.typhi specific primers(flagellin gene H1d and SOP E gene) could detect 0.6 ng of S.typhi DNA.Fifty-four patients with GBC(cases) were matched with 54 patients with GSD(controls).RESULTS:Of the 54 cases,24(44.44%) were positive on the Widal test and 12(22.22%) on IHA,compared to 13(24.07%) and 5(9.26%) respectively in the controls.Eighteen(33.33%) cases showed a positive result on PCR(tissue) and 2 on PCR(bile) vs.none in the controls.Bile culture revealed no Salmonella colonies in either cases or controls.Only 3 cases were positive for Salmonella on tissue culture compared to none in the controls.The sensitivity of PCR(tissue) relative to the Widal test,IHA,culture(bile and tissue) and PCR(bile) was 100% vs.66.67%,11.11%,and 11.11%,and the specificity was 83.33% vs.100%,100%,and 100%,respectively.CONCLUSIONS:S.typhi is significantly associated with GBC compared to GSD(33% vs.0%).PCR appears to be the most specific diagnostic tool,the gold standard for S.typhi in tissue samples.

Induction of deletion mutation on ompR gene of Salmonella enterica serovar Typhi isolates from asymptomatic typhoid carriers to evolve attenuated strains for vaccine development

Objective:To develop allenualed slrains of Salmonella enterica serorar Typhi(S.typhi) for the candidate vaccine by osmolar stress.Mothods:S.typhi SS3 and SS5 strains were isolated from asymptomatic typhoid carriers in Mamakkal,Tamil Nadu.India.Both strains were grown in LB(Luria Bertani) medium supplemented with various concentration of NaCl(0.1- 0.7M) respectively.The effecl of osmolar stress was determined at molecular level by PCR using MCR 06 and MCR07 primers corresponding to ompR with chromosomal DNA of S.typhi SS3 and SS5 strains.Attenuation by osmolar stress results in deletion mutation of the.S.typhi slrains was determined by agglutination assays,precipitation method.SDS PAGE analysis and by animal models.Results:The 799 bp amplified ompR gene product from wild type S.typhi SS3 and SS5 illustrate the presence of virulent gene.Interestingly,there was only a 282 bp amplified product from S.typhi SS3 and SS5 grown in the presence of 0.5.0.6 and 0.7 M NaCl.This illustrates the occurrence of deletion mutation in ompR gene al high concentration of NaCl.Furthermore,both the wildtype and mutant S.typhi outer membrane SDS-PAGF.profile reveals the differences in the expression of ompF.ompC and ompA proteins.In mice,wild type and mutant strains lethal dose(LD_(50)) were determined.The mice died within 72 h when both the wild type strains were injected intraperitoneally with 3 log CFU-mL^(-1).When the mice were injected with the mutants in same dosage,no clinical symptoms were observed;whereas the serum antibodv litre was elicited within two weeks indicated that the mutants have the ability to induce protective humoral immune response.These results suggest that S.typhi SS3 and SS5 may bo used as good candidate strains for the development of live attenuated vaccine against salmonellosis.Conclusions:This study demonstrates that the S.typhi strains were allenualed and could be good vaccine candidates in future.

Using a Surface Plasmon Resonance Biosensor for Rapid Detection of Salmonella Typhimurium in Chicken Carcass

Chicken is one of the most popular meat products in the world. Salmonella Typhimurium is a common foodbome pathogens associated with the processing of poultry. An optical Surface Plasmon Resonance （SPR） biosensor was sensitive to the presence of Salmonella Typhimurium in chicken carcass. The Spreeta biosensor kits were used to detect Salmonella Typhimurium on chicken carcass successfully. A taste sensor like electronic tongue or biosensors was used to basically ＂taste＂ the object and differentiated one object from the other with different taste sensor signatures. The surface plasmon resonance biosensor has potential for use in rapid, real-time detection and identification of bacteria, and to study the interaction of organisms with dif- ferent antisera or other molecular species. The selectivity of the SPR biosensor was assayed using a series of antibody con- centrations and dilution series of the organism. The SPR biosensor showed promising to detect the existence of Salmonella Typhimurium at 1 x 106 CFU/ml. Initial results show that the SPR biosensor has the potential for its application in pathogenic bacteria monitoring. However, more tests need to be done to confirm the detection limitation.

Oral Immunization of Mice With Vaccine of Attenuated Salmonella typhimurium Expressing Helicobacter pylori Urease B Subunit

Objective To prepare the live recombinant vaccine of attenuated Salmonella typhimurium SL3261 expressing Helicobacterpylori （H. pylori） B subunit （UreB） and to determine whether it could be used as an oral vaccine against H. pylori infection. Methods Using genomic DNA of H. pylori Sydney strain （SS1） as template, the H. pylori UreB gene fragment was amplified by PCR and subcloned into the expression vector pTC01. The recombinant plasmid pTC01-UreB was then transferred into LBS000 to obtain modified forms, and further conversed into the attenuated Salmonella typhimurium SL3261 to obtain recombinant SL3261/pCT01-UreB as an oral immunization reagent, which was then used to orally immunize Balb/c mice twice at a three-week interval. Twelve weeks later, anti-UreB IgA antibodies in intestinal fluid and IgG antibodies in sera were determined by ELISA. The relating data in control groups （including body weight, gastric inflammation, etc.） were also collected. Results The sequencing analysis showed that the UreB gene fragment amplified by PCR was consistent with the sequence of the H. pylori UreB gene. The restriction enzyme digestion revealed that the correct pTC01-UreB was obtained. SDS-PAGE and Western blot showed that a 61KD protein was expressed in SL3261/pTC01-UreB, which could be recognized by anti-H, pylori UreB antiserum and was absent in the control containing only Salmonella typhimurium SL3261 strain. The multiple oral immunization with SL3261/pTC01-UreB could significantly induce H. pylori specific mucosal IgA response as well as serum IgG responses. IFN-T and IL-10 levels were significantly increased in SL3261/pTC01-UreB group, and no obvious side effect and change in gastric inflammation were observed. Conclusion The attenuated vaccine of Salmonella typhimurium expressing H. pylori UreB can be used as an oral vaccine against H. pylori infection.

Detection of Salmonella typhimurium in retail chicken meat and chicken giblets

Objective:To detect Salmonella typhimurium(S.typhimurium),one of the most frequently isolated serovars from food borne outbreaks throughout the world,in retail raw chicken meat and giblets.Methods:One hundred samples of retail raw chicken meat and giblets(Liver,heart and gizzard)which were collected from Assiut city markets for detection of the organism and by using Duplex PCR amplification of DNA using rfbj andfliC genes.Results:S.typhimurium was detected at rate of 44%,40%and 48%in chicken meat,liver and heart,respectively,but not detected in gizzard.Conclusions:The results showed high incidence of 5.typhimurium in the examined samples and greater emphasis should be applied on prevention and control of contamination during processing for reducing food-borne risks to consumers.

Construction of recombinant attenuated Salmonella typhimurium DNA vaccine expressing H pylori ureB and IL-2

AIM： To construct a recombinant live attenuated Salmonella typhimurium DNA vaccine encoding H pylori ureB gene and mouse IL-2 gene and to detect its immunogenicity in vitro and in vivo. METHODS： Hpylori ureB and mouse IL-2 gene fragments were amplified by polymerase chain reaction （PCR） and cloned into pUCmT vector. DNA sequence of the amplified ureB and IL-2 genes was assayed, then cloned into the eukaryotic expression vector pIRES through enzyme digestion and ligation reactions resulting in pIRES-ureB and pIRES-ureB-IL-2. The recombinant plasmids were used to transform competent E. co/i DH5α, and the positive clones were screened by PCR and restriction enzyme digestion. Then, the recombinant pIRES-ureB and pIRES-ureB-IL-2 were used to transform LB5000 and the recombinant plasmids extracted from LB5000 were finally introduced into the final host SL7207. After that, recombinant strains were grown in vitro repeatedly. In order to detect the immunogenicib/of the vaccine in vitro, pIRES-ureB and pIRES-ureB-IL-2 were transfected to COS-7 cells using LipofectamineTM2000, the immunogenicity of expressed UreB and IL-2 proteins was assayed with SDS-PAGE and Western blot. C57BL/6 mice were orally immunized with 1 × 10^8 recombinant attenuated Salmonella typhimurium DNA vaccine. Four weeks after vaccination, mice were challenged with 1 × 10^7 CFU of live Hpylori SS1. Mice were sacrificed and the stomach was isolated for examination of H pylon 4 wk post-challenge. RESULTS： The 1700 base pair ureB gene fragment amplified from the genomic DNA was consistent with the sequence of H pylori ureB by sequence analysis. The amplified 510 base pair fragment was consistent with the sequence of mouse IL-2 in gene bank. It was confirmed by PCR and restriction enzyme digestion that H pylori ureB and mouse IL-2 genes were inserted into the eukaryotic expression vector pIRES. The experiments in vitro showed that stable recombinant live attenuated Salmonella typhimurium DNA vaccine carrying ureB and IL-2 genes was successfully constructed and the specific strips of UreB and IL-2 expressed by recombinant plasmids were detected through Western blot. Study in vivo showed that the positive rate of rapid urease test of the immunized group including ureB and ureB-IL-2 was 37.5% and 12.5% respectively, and was significantly lower than that （100%） in the control group （P 〈 0.01）. CONCLUSION： Recombinant attenuated Salmonella typhimurium DNA vaccine expressing UreB protein and IL-2 protein with immunogenicity can be constructed. It can protect mice against H pylori infection, which may help the development of a human-use H pylori DNA vaccine.

Effect of Ocimum sanctum on the development of protective immunity against Salmonella typhimurium infection through cytokines

Objective:To investigate the protective role of Ocimum sanctum（O.sanctum） leaves against Salmonella typhim.urium（S.typhimurium） infection in rats by inducing TNF-α,IFN-γ& IL-2 cytokines.Methods:Wistar albino rats were fed with aqueous extract of 0.sanctum leaves using 250 mg/kg body weight dose once a day for 20 consecutive days.Control rats were fed with placebo.Rats were infected with LD50 dose of 5.typhimurium infection and monitored for their survival.Bacterial blood burden in both the groups was compared and numbers of activated peritoneal macrophages were counted.Concentration of TNF-α,IFN-γand IL-2 cytokines in serum during different time intervals was assayed by sandwich ELISA.Results:Rats of control group showed a high mortality rate and had higher bacterial blood burden when compared with O.sanctum extract fed rats.There was a significant increase in the number of S.typhimurium engulfed peritoneal macrophages in the peritoneal fluid of O.sanctum fed animals.The protective control against bacterial infection in O,sanctum fed rats was associated with elevated level of TNF-α,IFN-γand IL-2 cytokines in serum.Conclusions:These findings suggest that orally administered O.sanctum leaves extract effectively enhanced activation in macrophage and lymphocytes,depicted by the elevated serum concentration of TNF-α,IFN-γand IL-2 cytokines,leading to induce a protective resistance against Salmonella typhimurium infection.

Comparative Study on Bactericidal Effect of Silver Nanoparticles, Synthesized Using Green Technology, in Combination with Antibiotics on Salmonella Typhi

In this work bactericidal study of silver nanoparticles was taken up in combination with two standard antibiotics, ampicillin and gentamycin, for Salmonella Typhi. The antibacterial activities of antibiotics were increased in the presence of AgNPs against test strains. The higher enhancing effect was observed for ampicillin in comparison to gentamicin against test strains. Silver nanoparticles were synthesized elctrolytically using silver wire of 99% purity as anode and carbon rod wrapped with LDPE as cathode. Silver nitrate [of Merck] of 0.01N is used as an electrolyte. Here tea extract is added as capping and mild reducing agent. The polyphenols theaflavins and thearubigins, present in tea perform the role of stabilizing or capping agents due to their bulky and steric nature. A brown coloured colloidal solution of silver nanoparticles is obtained. The as-synthesized silver nanoparticles were characterized using XRD, TEM and UV-Vis spectroscopy.

Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer

AIM: To develop an oral attenuated Salmonella typhimurium vaccine against gastric cancer and to evaluate its efficacy in mice. METHODS: A complementary sequence of Nco Ⅰ site and a sequence coding for MG7-Ag mimotope were designed at the 5'terminus of forward primer. Using p1.2 Ⅱ-HBCAg plasmid as template, PCR was performed to get a fusion gene of the mimotope and a HBcAg gene. The fusion gene was then subcloned into the plasmid pYA3341 complementary to Salmonella typhimurium X4550, and the recombinant plasmid was then transformed into attenuated Salmonella typhimurium X4550. Balb/c mice were orally immunized with the recombinant Salmonella typhimurium X4550. The mice were immunized every 2 wk to reinforce the immunity. At the 6th wk, serum titer of antibody was detected by ELISA, and at the 8th wk, cellular immunity was detected by 51Cr release test. Ehrlich ascites carcinoma cells expressing MG7-Ag were used in tumor challenge assay as a model to evaluate the protective effect of the vaccine. RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than in control groups (0.9538±0.043 vs 0.6531±0.018, P<0.01; 0.9538±0.043 vs 0.6915±0.012, P<0.01), while in vitro 51Cr release assay of the splenocytes showed no statistical difference in the three groups. Two weeks after tumor challenge, 1 in 5 immunized mice was tumor free, while all the mice in the control group presented tumor. CONCLUSION: Oral attenuated Salmonella typhimurium vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumors in mice, and has some protective effects.

Immunogenicity of recombinant attenuated Salmonella typhimurium expressing a 45-peptide hybrid antigen gene of Plasmodium falciparum

A synthetic hybrid 45-peptide gene of Plasmodium falciparum (Pf), which encoded two CSP repeated peptides NANP and three merozoite peptides SPf83. 1, SPf55. 1 and SPf35. 1, was cloned in an expression vector pWR450-1, then the recombinant plasmid pWRA was introduced into the attenuated Salmonella typhimurium SL3261. When used as a live vaccine and administered orally (po), intravenously (iv) or intraperitoneally (ip),the recombinant strain was able to live in vivo and elicit specific humoral and cellular immunity in BALB/c mice and rabbits. As oral immunization is safe and effective, it is thought that the live recombinant Salmonella tyPhimurium vaccine may bring the Pf oral live vaccine a step nearer.

Systemic immune responses to oral administration of recombinant attenuated Salmonella typhimurium expressing Helicobacter pylori urease in mice

AIM:To evaluate whether attenuated Salmonella typhimurium producing Helicobacter pylori(H pylori) urease subunit B (UreB) could induce systemic immune responses against Hpylori infection. METHODS: Attenuated 5. typhimurium SL3261 was used as a live carrier of plasmid pTC01-UreB, which encodes recombinant H pylori UreB protein. Balb/c mice were given oral immunization with two doses of SL3261/pTC01-UreB at a 3-wk interval. Twelve weeks after oral immunization of mice, serum IgG antibodies were evaluated by ELISA assay. Gamma interferon (IFN-γ) and interleukin 10 (IL-10) in the supernatant of spleen cell culture were also assessed by ELISA. RESULTS: After oral immunization of mice, serum specific IgG antibodies against UreB in vaccine group were much higher than that in PBS and native Salmonella SL3261 control groups (A450, 0.373±0.100 vs 0.053±0.022, 0.142±0.039, respectively, P<0.01). Moreover, IFN-γ in vaccine group was on average 167.53±29.93 pg/mL, which showed a significant increase vs that of PBS control group (35.68±3.55 pg/mL, P<0.01). There was also a tremendous increase of IL-10 in vaccine group compared to PBS and SL3261 control groups (275.13±27.65 pg/mL vs 56.00±7.15 pg/mL, 68.02±15.03 pg/mL, respectively, P<0.01). In addition, no obvious side effects in mice and no change in gastric inflammation were observed. CONCLUSION: The multiple oral immunizations with the attenuated 5. typhimurium expressing Hpylori UreB could induce significant systemic immune responses, suggesting it may be used as oral vaccine against H pylori infection.

Genomic Epidemiology of ST34 Monophasic Salmonella enterica Serovar Typhimurium from Clinical Patients from 2008 to 2017 in Henan,China

Salmonella enterica serovar 4,[5],12:i:-(S.4,[5],12:i:-)is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern.To date,the epidemiology and genomic characterization of this pathogen in China have not been well described.We investigated the prevalence,antimicrobial resistance(AMR)phenotypes,and population genomics of sequence type 34(ST34)S.4,[5],12:i:-among cases of human salmonellosis in Henan Province,China.A total of 100 ST34 S.4,[5],12:i:-isolates were studied from 2008 to 2017 and found mostly resistant to ampicillin(AMP),streptomycin(STR),sulfonamides(SUL),and tetracycline(TET)(ASSu T).Bayesian phylogenetic analysis demonstrated that isolates identified in China were mostly related to the European lineage and evolved into two major clades with different resistance genes and plasmid profiles.Notably,clade 1 showed a significantly higher rate of mutations in gyr A and plasmid-mediated quinolone resistance genes.The carrying of the resistance-containing region(encoding R-type ASSu T),including bla(conferring resistance to AMP),str AB(STR),sul2(SUL),and tet(B)(TET)inserted into the flj BA operon,was responsible for most of the monophasic variants in clade 2.Inc HI2 plasmids were the dominant multi-drug resistance mobile genetic elements accounting for the transmission of acquired resistance genes in this serovar,and these were more prevalent in clade 1.Our findings highlighted the increasing prevalence of multi-drug resistant S.4,[5],12:i:-in China,along with the differential characteristics of resistance gene acquisition among various lineages.Based on our data,control measures are required to address the spread of this zoonotic pathogen.Further owing to its potential origin in food-producing animals,a"One Health"approach,should be implemented to support surveillance whilst informing interventional strategies.

Pretreatment with probiotics Enterococcus faecium NCIMB 11181 attenuated Salmonella Typhimurium-induced gut injury through modulating intestinal microbiome and immune responses with barrier function in broiler chickens

Background:Preventing Salmonella infection and colonization in young birds is key to improving poultry gut health and reducing Salmonella contamination of poultry products and decreasing salmonellosis for human consumption(poultry meat and eggs).Probiotics can improve poultry health.The present study was conducted to investigate the impact of a probiotics,Enterococcus faecium NCIMB 11181(E.faecium NCIMB 11181)on the intestinal mucosal immune responses,microbiome and barrier function in the presence or absence of Salmonella Typhimurium(S.Typh-imurium,ST)infection.Methods:Two hundred and forty 1-day-old Salmonella-free male broiler chickens(Arbor Acres AA+)were randomly allocated to four groups with 6 replicate cages of 10 birds each.The four experimental groups were follows:(1)nega-tive control(NC),(2)S.Typhimurium,challenged positive control(PC),(3)the E.faecium NCIMB 11181-treated group(EF),(4)the E.faecium NCIMB 11181-treated and S.Typhimurium-challenged group(PEF).Results:Results indicated that,although continuous feeding E.faecium NCIMB 11181 did not obviously alleviate growth depression caused by S.Typhimurium challenge(P>0.05),E.faecium NCIMB 11181 addition significantly blocked Salmonella intestinal colonization and translocation(P<0.05).Moreover,supplemental E.faecium NCIMB 11181 to the infected chickens remarkably attenuated gut morphological structure damage and intestinal cell apoptosis induced by S.Typhimurium infection,as evidenced by increasing gut villous height and reducing intes-tinal TUNEL-positive cell numbers(P<0.05).Also,E.faecium NCIMB 11181 administration notably promoting the production of anti-Salmonella antibodies in intestinal mucosa and serum of the infected birds(P<0.05).Addition-ally,16S rRNA sequencing analysis revealed that E.faecium NCIMB 11181 supplementation ameliorated S.Typhimu-rium infection-induced gut microbial dysbiosis by enriching Lachnospiracease and Alistipes levels,and suppressing Barnesiella abundance.Predicted function analysis indicated that the functional genes of cecal microbiome involved in C5-branched dibasic acid metabolism;valine,leucine and isoleucine biosynthesis;glycerolipid metabolism and lysine biosynthesis were enriched in the infected chickens given E.faecium NCIMB 11181.While alanine,asparate and glutamate metabolism;MAPK signal pathway-yeast;ubiquine and other terpenoid-quinore biosynthesis,protein processing in endoplasmic reticulum;as well as glutathione metabolism were suppressed by E.faecium NCIMB 11181 addition.Conclusion:Collectively,our data suggested that dietary E.faecium NCIBM 11181 supplementation could ameliorate S.Typhimurium infection-induced gut injury in broiler chickens.Our findings also suggest that E.faecium NCIMB 11181 may serve as an effective non-antibiotic feed additive for improving gut health and controlling Salmonella infection in broiler chickens.

Fulminant hepatic failure caused by Salmonella paratyphi A infection

We report a case of fulminant hepatic failure associated with Salmonella paratyphi A infection, in a 29-yearold patient who was admitted to the intensive care unit （ICU） with fever of two days, headache and vomiting followed by behavioural changes and disorientation. On examination, the patient appeared acutely ill, agitated, confused, and deeply jaundiced. Temperature 38.5℃, pulse 92/min, blood pressure 130/89 mmHg. Both samples of blood grew S. paratyphi A, which was sensitive to ceftriaxone and ciprofloxacin. Ceftriaxon was administered with high-dose dexamethasone. Two weeks after treatment with ceftriaxon, the patient was discharged in satisfactory condition.

Immunogenicity and protective efficacy of DHBV DNA vaccines expressing envelope and capsid fusion proteins in ducks delivered by attenuated Salmonella typhimurium

Duck hepatitis B virus(DHBV) shares many basic characteristics with hepatitis B virus(HBV) and is an attractive model for vaccine development. In this study, DHBV DNA vaccines were designed to express envelope and capsid fusion proteins to enhance the breadth of immune response in ducks. Attenuated Salmonella typhimurium(SL7207) was used as a carrier and adjuvant to boost the magnitude of immune response. Based on this strategy, novel DNA vaccines(SL7207-p VAX1-LC and SL7207-p VAX1-SC) were generated. Growth kinetics, genetic stabilities and relative transcription levels of the L, S and C genes introduced by these vaccine strains were measured before inoculation to guarantee safety and efficacy. The relative transcript levels of the CD4 and CD8 T genes and the antibody levels(Ig Y) in ducks receiving the vaccines were higher than those in single gene delivered groups. Additionally, the copy number of covalently closed circular DNA in hepatocytes after DHBV challenge also provided evidence that our fusion vaccines could enhance the protective efficiency against DHBV infection in ducks.