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Two bacteriophages specifically active against to pathogenic strains of the Salmonella genus were isolated. The morphology of phage colonies (size, transparency, and shape of the plaque edge, and halo) and the spectrum of their lytic activity and interaction with microbial cells (adsorption rate, duration of the latency, and reproductive efficiency) were examined. Using genome-wide sequencing, we determined the taxonomic position of bacteriophages and verified the absence of unwanted genes encoding toxins, adhesins, and invasins, as well as pathogenicity islands responsible for antibiotic resistance. In addition, phage stability under different physical conditions and their productivity were studied., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The ability of virulent bacteriophages to lyse bacteria influences bacterial evolution, fitness, and population structure. Knowledge of both host susceptibility and resistance factors is crucial for the successful application of bacteriophages as biological control agents in clinical therapy, food processing, and agriculture. In this study, we isolated 12 bacteriophages termed SPLA phage which infect the foodborne pathogen Salmonella enterica . To determine phage host range, a diverse collection of Enterobacteriaceae and Salmonella enterica was used and genes involved in infection by six SPLA phages were identified using Salmonella Typhimurium strain ST4/74. Candidate host receptors included lipopolysaccharide (LPS), cellulose, and BtuB. Lipopolysaccharide was identified as a susceptibility factor for phage SPLA1a and mutations in LPS biosynthesis genes spontaneously emerged during culture with S . Typhimurium. Conversely, LPS was a resistance factor for phage SPLA5b which suggested that emergence of LPS mutations in culture with SPLA1a represented collateral sensitivity to SPLA5b. We show that bacteria-phage co-culture with SPLA1a and SPLA5b was more successful in limiting the emergence of phage resistance compared to single phage co-culture. Identification of host susceptibility and resistance genes and understanding infection dynamics are critical steps in the rationale design of phage cocktails against specific bacterial pathogens.IMPORTANCEAs antibiotic resistance continues to emerge in bacterial pathogens, bacterial viruses (phage) represent a potential alternative or adjunct to antibiotics. One challenge for their implementation is the predisposition of bacteria to rapidly acquire resistance to phages. We describe a functional genomics approach to identify mechanisms of susceptibility and resistance for newly isolated phages that infect and lyse Salmonella enterica and use this information to identify phage combinations that exploit collateral sensitivity, thus increasing efficacy. Collateral sensitivity is a phenomenon where resistance to one class of antibiotics increases sensitivity to a second class of antibiotics. We report a functional genomics approach to rationally design a phage combination with a collateral sensitivity dynamic which resulted in increased efficacy. Considering such evolutionary trade-offs has the potential to manipulate the outcome of phage therapy in favor of resolving infection without selecting for escape mutants and is applicable to other virus-host interactions., Competing Interests: Quadram Institute Bioscience has filed a provisional patent application no: 2310148.8 related to this work.

Background: Salmonella enterica serotype Typhi is one of the major pathogens causing typhoid fever and a public health burden worldwide. Recently, the increasing number of multidrug-resistant strains of Salmonella spp. has made this utmost necessary to consider bacteriophages as a potential alternative to antibiotics for S. Typhi infection treatment. Salmonella phage STWB21, isolated from environmental water, has earlier been reported to be effective as a safe biocontrol agent by our group. In this study, we evaluated the efficacy of phage STWB21 in reducing the burden of salmonellosis in a mammalian host by inhibiting Salmonella Typhi invasion into the liver and spleen tissue., Results: Phage treatment significantly improved the survival percentage of infected mice. This study also demonstrated that oral administration of phage treatment could be beneficial in both preventive and therapeutic treatment of salmonellosis caused by S. Typhi. Altogether the result showed that the phage treatment could control tissue inflammation in mice before and after Salmonella infection., Conclusions: To the best of our knowledge, this is the first report of phage therapy in a mouse model against a clinically isolated Salmonella Typhi strain that includes direct visualization of histopathology and ultrathin section microscopy images from the liver and spleen sections., (© 2023. The Author(s).)

Salmonella, is one of the bacterial genera having more than 2500 serogroups is one of the most prominent food borne pathogen that is capable of causing disease out breaks among humans and animals. Recent reports clearly shows that this pathogen is evolved and it developed drug resistant towards most of the commercially available antibiotics. In order to overcome this emerging resistance, Bacteriophage therapy is one of the alternative solutions. It is more pathogen specific, high potency, and thereby highly safe for consumption. This chapter discuss about Rapid screening and Detection Methods Associated with Bacteriophage for Salmonella, commercially available phage products and regulatory status, Salmonella endolysins and future prospects of phage therapy., (Copyright © 2023. Published by Elsevier Inc.)

Salmonella infection is a major public health concern. Several strategies for Salmonella infection prevention and control are currently available including vaccines and antibiotics. However, vaccines are expensive and inefficient, and the use of antibiotics can lead to antibiotic resistance. Thus, alternative strategies for the treatment of Salmonella remain warrant. In this study, recombinant holin HolST-3 and lysin LysST-3 from Salmonella phage ST-3 were expressed and purified, and their bactericidal properties were analyzed. HolST-3 and LysST-3 possessed a wider lysis spectrum and more efficient bactericidal effect than phage ST-3, and a synergistic bactericidal effect was observed when combined in vitro. In addition, we explored the bactericidal properties of HolST-3 and LysST-3 in vivo using zebrafish as a model organism, and found that the bactericidal effects of both HolST-3 and LysST-3 in vivo were comparable to those of cefotaxime, an antibiotic. This study provides a basis for the development of HolST-3 and LysST-3 as novel bactericidal agents for the prevention and treatment of infectious diseases caused by Salmonella spp., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

BACKGROUND Rhabdomyolysis is a clinical syndrome characterized by elevated serum creatine kinase (CK) and myoglobin levels due to the breakdown of muscle fibers and is associated with symptoms such as myalgia, muscle swelling, and erythruria. Rhabdomyolysis has an array of potential causes, including Salmonella infection, although rare. We report 2 cases in which nontyphoidal salmonellae caused acute gastroenteritis complicated by rhabdomyolysis and myoglobinuric acute kidney injury (AKI). CASE REPORT Two male patients, aged 69 years and 62 years, presented to our hospital with sudden-onset fever, abdominal pain, and watery diarrhea. At the time of admission, the patients had elevated serum CK levels (32 225 U/L and 10 590 U/L, respectively) and serum creatinine levels (4.8 mg/dL and 8.8 mg/dL, respectively). Both patients also had elevated serum myoglobin concentrations with significant myoglobinuria. They were administered fluid therapy and intravenous empirical antibiotics (cefotaxime and metronidazole for Case 1, ciprofloxacin for Case 2). The patient in Case 2 underwent 3 sessions of hemodialysis due to persistent oliguria and exacerbation of metabolic acidosis. Salmonella B (Case 1) and Salmonella C (Case 2) were isolated from blood cultures. After about 2 weeks of inpatient care, both patients showed improvement of clinical symptoms and were discharged. CONCLUSIONS Patients with acute gastroenteritis induced by Salmonella infection can develop rhabdomyolysis and myoglobinuric AKI in rare cases. Timely administration of appropriate antibiotics and fluids is expected to produce a favorable prognosis. Furthermore, early initiation of hemodialysis after onset of oliguric AKI can improve clinical outcomes.

Salmonella is a gram-negative, motile, nonsporulating, facultative anaerobic bacillus, belongs to the family Enterobacteriaceae. The bacteria were first identified in 1884. It is transmitted through direct contact with an infected person or indirect contact by the consumption of contaminated food and water. More than 2500 serotypes of Salmonella enterica have been identified but less than 100 serotypes are known to cause infections in humans. S. enterica serovar typhi (S. typhi) and S. enterica serovar paratyphi (S. paratyphi A B C) cause enteric fever, whereas nontyphoidal Salmonella serotypes (NTS) cause diarrhea. NTS commonly presents with gastroenteritis and is a self-limiting disease. Enteric fever is a potentially life-threatening acute febrile systemic infection and is diagnosed by isolating a pathogen on culture. With the emergence of the extensive drug-resistant (XDR) S. typhi clone, limited treatment options are available. Vaccination of persons at risk, improvement of sanitation, promotion of food hygiene, and detection and control of chronic carriers are essential preventive control measures of enteric fever., Competing Interests: Disclosure The authors have no conflict of interest, nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Salmonella Typhimurium, a foodborne pathogen, is a major concern for food safety. Its MDR serovars of animal origin pose a serious threat to the human population. Phage therapy can be an alternative for the treatment of such MDR Salmonella serovars. In this study, we report on detailed genome analyses of a novel Salmonella phage ( Salmonella -Phage-SSBI34) and evaluate its therapeutic potential. The phage was evaluated for latent time, burst size, host range, and bacterial growth reduction in liquid cultures. The phage stability was examined at various pH levels and temperatures. The genome analysis (141.095 Kb) indicated that its nucleotide sequence is novel, as it exhibited only 1-7% DNA coverage. The phage genome features 44% GC content, and 234 putative open reading frames were predicted. The genome was predicted to encode for 28 structural proteins and 40 enzymes related to nucleotide metabolism, DNA modification, and protein synthesis. Further, the genome features 11 tRNA genes for 10 different amino acids, indicating alternate codon usage, and hosts a unique hydrolase for bacterial lysis. This study provides new insights into the subfamily Vequintavirinae , of which SSBI34 may represent a new genus.

Aims: The composition, overtly abundance, and diversity of gut microbiota, play a significant role in maintaining physiological homeostasis with age. Reports revealed that the gut microbial profile might be correlated with immunity and metabolism. It is, therefore, tantamount to know if an older individual can achieve the immunity and metabolic profile of a younger individual by receiving the gut microbiome of a younger individual. In the current report, we have studied the effects of cecal microbiota transplantation (CMT) from younger to older mice., Materials and Methods: In this study, older BALB/c mice (23 weeks) received CMT from younger BALB/c mice (3 weeks)., Key Findings: CMT recipient mice showed altered expressions of immune and tight junction protein genes in the colon of mice, while the non-CMT recipient mice did not. Older mice were treated with AVNM to make them compatible with CMT. Further data from metabolite studies revealed that AVNM treatment mainly affected the aromatic amino acid biosynthesis pathway while CMT mostly affected the metabolism of different carbohydrates. We repeated the analysis in C57BL/6 mice without any significant effects of CMT., Significance: Results revealed that mice who received CMT showed more efficient restoration of gut microbiota than non-CMT recipient mice. CMT caused the alleviation of Salmonella infection and efficient recovery of the cecal index in the mice following antibiotics treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nontyphoidal Salmonella (NTS) gastroenteritis in children remains a significant burden on health care and constitutes a majority of all admissions for Salmonella infections in public hospitals in Hong Kong. In this prospective study, 41% of 241 children hospitalized with gastroenteritis from three public hospitals during 2019 were culture confirmed to have NTS infection. These Salmonella isolates were whole-genome sequenced and in silico predicted for their serovars/serotypes using the Salmonella In Silico Typing Resource (SISTR) and SeqSero1, and the antimicrobial resistance (AMR) genes were determined. Phylogenetic analysis revealed three major clades belonging to Salmonella enterica serovar Enteritidis sequence type 11 (ST11) (43%), multidrug-resistant (MDR) S. Typhimurium ST19 (12%) and its monophasic variant ST34 (25%), and mostly singletons of 15 other serovars. MDR S. Typhimurium and its variant were more common in infants <24 months of age and possessed genotypic resistance to five antimicrobial agents, including ampicillin (A), chloramphenicol (C), aminoglycosides (Am), sulfonamides (Su), and tetracyclines (T). Older children were more often infected with S. Enteritidis, which possessed distinct genotypic resistance to AAmSu and fluoroquinolones. In addition, 3% of the isolates possessed extended-spectrum beta-lactamase (ESBL) CTX-M genes, while one isolate (1%) harboring the carbapenemase gene bla NDM-1 was identified. Our findings provide a more complete genomic epidemiological insight into NTS causing gastroenteritis and identify a wider spectrum of determinants of resistance to third-generation beta-lactams and carbapenems, which are often not readily recognized. With high rates of multidrug-resistant NTS from studies in the Asia-Pacific region, the rapid and reliable determination of serovars and resistance determinants using whole-genome sequencing (WGS) is invaluable for enhancing public health interventions for infection prevention and control. IMPORTANCE Nontyphoidal Salmonella (NTS) gastroenteritis is a foodborne disease with a large global burden. Antimicrobial resistance (AMR) among foodborne pathogens is an important public health concern, and multidrug-resistant (MDR) Salmonella is prevalent in Southeast Asia and China. Using whole-genome sequencing, this study highlights the relationship of the MDR Salmonella serotypes and the diverse range of Salmonella genotypes that contaminate our food sources and contribute to disease in this locality. The findings update our understanding of Salmonella epidemiology and associated MDR determinants to enhance the tracking of foodborne pathogens for public health and food safety.

Bacteriophages that lyse Salmonella enterica are potential tools to target and control Salmonella infections. Investigating the host range of Salmonella phages is a key to understand their impact on bacterial ecology, coevolution and inform their use in intervention strategies. Virus-host infection networks have been used to characterize the "predator-prey" interactions between phages and bacteria and provide insights into host range and specificity. Here, we characterize the target-range and infection profiles of 13 Salmonella phage clones against a diverse set of 141 Salmonella strains. The environmental source and taxonomy contributed to the observed infection profiles, and genetically proximal phages shared similar infection profiles. Using in vitro infection data, we analyzed the structure of the Salmonella phage-bacteria infection network. The network has a non-random nested organization and weak modularity suggesting a gradient of target-range from generalist to specialist species with nested subsets, which are also observed within and across the different phage infection profile groups. Our results have implications for our understanding of the coevolutionary mechanisms shaping the ecological interactions between Salmonella phages and their bacterial hosts and can inform strategies for targeting Salmonella enterica with specific phage preparations.

The aim of this systematic review was to characterize the clinical features of adults with Salmonella osteomyelitis and summarize diagnosis and treatment methods to provide guidance for clinicians. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a literature search in the PubMed, EMBASE, and Cochrane Library databases. Article screening and data extraction were performed by two reviewers individually. All the included studies were independently evaluated by two reviewers using the Methodological Index for Non-Randomized Studies (MINORS) criteria. A total of 67 articles published between 1970 and 2019 were selected, which include 69 patients with an average age of 47.5 years (range, 18-79).The majority of cases (47.76%) occurred in immunocompetent adults without common risk factors. Aspiration and biopsy cultures were all positive in Salmonella osteomyelitis patients who underwent aspiration or biopsy. All infections were monomicrobial, and a total of 12 different serotypes were identified. The three most commonly reported Salmonella serotypes were Salmonella typhi (19 cases), Salmonella typhimurium (12 cases), and Salmonella enteritidis (11 cases). Only 12 of the 67 cases in our data (17.91%) had diarrhea symptoms, and 44 of the 67 cases (65.67%) had fever symptoms. Fifty-nine of the 67 cases (88.06%) had local inflammatory manifestations, such as erythema, swelling, and tenderness in the affected area. The commonly reported involved sites were the vertebrae, femur, and tibia. Antibiotic therapy alone was utilized in 30 cases, and 24 patients (80.00%) were eventually cured. In total, 75.68% of patients achieved satisfactory results after treatment with surgery and antibiotics. Third-generation cephalosporins were most commonly utilized, and antibiotic treatment was administered for an average of 11.3 weeks (95% CI, 8.31-14.37 weeks). Salmonella osteomyelitis should be considered in patients without any common risk factors. Aspiration or biopsy can facilitate the identification of pathogens to guide antibiotic choice. Empirical therapy with a third-generation cephalosporin is recommended until the susceptibility of the strain is determined., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in Sub-Saharan Africa. Here, we isolated and characterised 32 phages capable of infecting S . Typhimurium and S . Enteritidis, from water sources in Malawi and the UK. The phages were classified in three major phylogenetic clusters that were geographically distributed. In terms of host range, Cluster 1 phages were able to infect all bacterial hosts tested, whereas Clusters 2 and 3 had a more restricted profile. Cluster 3 contained two sub-clusters, and 3.b contained the most novel isolates. This study represents the first exploration of the potential for phages to target the lineages of Salmonella that are responsible for bloodstream infections in Sub-Saharan Africa.

Adoptive transfer therapy has great potential to treat diseases such as cancer as well as autoimmune and infectious diseases. Identification of chain-centric T cell receptors (TCRs) with the dominant-active antigen-specific α-chains (TCRα) can significantly improve the efficacy of adoptive cell therapy while reducing time, labor, and costs of generation of TCR-modified antigen-specific T cells. This protocol describes how to generate salmonella-specific TCRα-modified mouse T cells by retroviral transduction and evaluate their functional activity in vivo in the mouse model of salmonellosis. For complete details on the use and execution of this protocol, please refer to Kalinina et al. (2020)., Competing Interests: The authors have a patent of the Russian Federation related to this work (Kazansky, D.B., Khromykh, L.M., Kalinina, A.A., Silaeva, Y.Y., Zamkova, M.A., Bruter, A.V., Persiyantseva, N.A., Chikileva, I.O., Jolokhava, L.Kh., Nesterenko, L.N. et al. (2018). A method of creating anti-infectious immunologic defense against Salmonella typhimurium and Listeria monocytogenes by transgenesis of T lymphocytes. Patent #2706554)., (© 2021 The Authors.)

S. Enteritidis continues to be the most common pathogen of farm animals and a major public health burden worldwide. Using bacteriophages is a potential alternative to antibiotics against S. Enteritidis infection. In this study, the genome analysis of the lytic phage vB&#95;SenM-PA13076 (PA13076) infecting S. Enteritidis revealed a linear, double-stranded DNA genome, which comprised of 52,474 bp and contained 69 ORFs. It belongs to the order Caudovirales; family Myoviridae, genus unclassified. The genes coded for DNA packaging, phage structural proteins, lysis components, DNA recombination, regulation, modification, and replication. No bacterial virulence or drug-resistance genes were detected. The phage PA13076 protected mice from a lethal dose of S. Enteritidis 13076 Amp (5 × 10 8 CFU) by reducing the concentration of bacterial cells in blood, intestine, liver, spleen, and kidney. The phage PA13076 achieved at least 2.5 log reductions of S. Enteritidis cells in infected mice within 24 h (P < 0.05) when compared to the organs of control mice. The data also indicated that phage PA13076 could rapidly enter the blood and four organs of infected mice, remaining therein at concentrations of>10 4 PFU/g for at least 72 h. These results show that phage PA13076 has definite potential as an antibacterial therapeutic agent for attenuating S. Enteritidis infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Developing novel antimicrobials capable of controlling multidrug-resistant bacterial pathogens is essential to restrict the use of antibiotics. Bacteriophages (phages) constitute a major resource that can be harnessed as an alternative to traditional antimicrobial therapies. Phage ZCSE2 was isolated among several others from raw sewage but was distinguished by broad-spectrum activity against Salmonella serovars considered pathogenic to humans and animals. Lytic profiles of ZCSE2 against a panel of Salmonella were determined together with low temperature activity and pH stability. The morphological features of the phage and host infection processes were characterized using a combination of transmission electron and atomic force microscopies. Whole genome sequencing of ZCSE2 produced a complete DNA sequence of 53,965 bp. No known virulence genes were identified in the sequence data, making ZCSE2 a good candidate for phage-mediated biological control purposes. ZCSE2 was further tested against S. Enteritidis in liquid culture and was observed to reduce the target bacterium to below the limits of detection from initial concentrations of 10 7 -10 8 Colony Forming Units (CFU)/mL. With a broad host-range against pathogenic Salmonella serovars, phage ZCSE2 constitutes a potential tool against a major cause of human and animal disease.

Introduction: Salmonella enterica serotype Enteritidis (S. Enteritidis) is a cause of food-borne human illness. Given the prevalence of antibiotic resistance of Salmonella Enteritidis and the lack of antibiotic efficacy in future years, its replacement with other agents is necessary. One of the most useful agents is bacteriophages., Methods: S. Enteritidis was identified using a multiplex polymerase chain reaction assay. The effective bacteriophages were isolated from hospital wastewater samples. The effects of the bacteriophages were evaluated both in vitro and in vivo., Results: The phage SE20 belonged to the Podoviridae family, and the genome size was 40 kb. The evaluation of phage SE20 at variable pH ranges showed its susceptibility to pH < 3 and pH > 12. The animal model showed that mice infected with S. Enteritidis developed hepatomegaly and splenomegaly, but did not experience gastrointestinal complications after receiving the bacteriophages., Conclusions: The results of this study suggest that phage SE20 is a promising candidate for controlling salmonellosis caused by Salmonella Enteritidis.

For effective use of phages as antimicrobial agents for controlling multidrug resistant S. Pullorum, it is important to understand phage biology. A lytic S. Pullorum phage was isolated and characterized from chicken feces, and its whole genome was sequenced and analyzed. A new lytic phage-vB&#95;SPuM&#95;SP116 (in brief SP116)- isolated and characterized using S. Pullorum SPu-116 as its host belongs to Myoviridae A1 group. Phage SP116 had a lytic effect on 27 of 37 (72.9%) different serotypes of clinical Salmonella strains. It showed a high bactericidal activity in killing all pathogens in cultures containing 5 × 10 5  cfu/mL and achieved more than 6.58 and 5.97 log unit reductions in cultures containing 5 × 10 6  cfu/mL and 5 × 10 7  cfu/mL, respectively. The one-step growth curve showed that the burst size was up to 118 pfu/bacterial cell. Complete genome sequence analysis revealed a linear, double-stranded DNA genome of 87,510 bp with an average G + C content of 38.84%, including 128 predicted open reading frames (ORFs) and 22 tRNA genes. SP116 was classified as a Felix O1 virus based upon the general phage characterization and the genomic information. Regarding its high efficacy in preventing especially S. Pullorum infection and its lack of any bacterial virulence, antimicrobial resistance, and lysogenesis genes, it could be a potential alternative candidate for the treatment of S. Pullorum infections., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Salmonella typhimurium (S. t.) is one of the main pathogens that causes acute gastroenteritis. To evaluate the anti-inflammatory mechanism of Astragalus polysaccharide (APS) in vivo and its influence on the intestinal flora, BALB/c mice were infected with S. t. to establish a model of diarrhea. The disease activity index (DAI) scores showed that APS attenuated S. t.-induced weight loss and diarrhea in mice. APS significantly reduced the index of the liver and spleen as well as the ALT and AST levels in serum (P < 0.05). Hematoxylin and eosin (H&E) results indicated that APS significantly increased jejunum villus height and crypt depth and reduced the infiltration of inflammatory cells (P < 0.05). Additionally, APS increased the tight junction (TJ) proteins expression levels of ZO-1, Occludin and Claudin-1 in the jejunum. The results of 16S rDNA showed that APS significantly increased the number of Lactobacillus and Bifidobacterium spp. to normal levels (compared with the control group). In addition, APS significantly decreased the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17 in the jejunum (P < 0.01) as well as the proteins expression levels of COX-2 and iNOS (P < 0.05). Western blot confirmed that prefeeding with APS inhibited S. t.-induced expression of TLR4 and MyD88 in the jejunum and further inhibited nuclear factor-κB (NF-κB) activation, including the nuclear translocation of the p65 NF-κB subunit and the phosphorylation and degradation of IκB-α. This was the key to APS inhibition of the production of inflammatory factors and inflammatory mediators in the jejunum., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Salmonella in a breast abscess is uncommon, and Salmonella paratyphi A causing breast abscess is a rare entity. It has been reported post immunosuppression. We report here a 35-year-old woman with breast abscess caused by S. paratyphi A without obvious enteric fever-like symptoms. The case was managed with combined surgical and medical approach to treat the aetiology and focal infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives : Salmonellosis is a major foodborne bacterial infection throughout the world. Epidemiological surveillance is one of the key factors to reduce the number of infections caused by this pathogen in both humans and animals. The first outcome measure was the prevalence of non-typhoid Salmonella (NTS) infections between 2000 and 2017 among the population of the predominantly agricultural and touristic Polish region of Warmia and Masuria (WaM). The second outcome measure was the comparison of the NTS hospitalization rate of all registered NTS cases, an investigation of the monthly reports of infections, and the exploration of the annual minimal and maximal NTS infection number in WaM in the above-mentioned time period. The last outcome was a comparison of the prevalence of NTS infections in the region and in its administrative districts by considering both rural and urban municipalities three years before and three years after the accession of Poland into the European Union (EU) in 2004. Materials and Methods: The total number of infections and hospitalizations in the 19 districts of the WaM voivodship in Poland was registered monthly between 2000⁻2017 by the Provincial Sanitary-Epidemiological Station in Olsztyn, Poland. Results: Between 2000 and 2017, the number of diagnosed salmonellosis cases decreased significantly in WaM; the decrease was higher in urban districts than in rural ones, and the ratio of hospitalizations and the total number of NTS cases increased significantly across all districts. The lowest number of cases was reported in the winter months and was stable from 2007, whereas the highest number was reported in the summer months with a higher tendency of outbreaks. Conclusion : The falling number of salmonellosis cases in 2000⁻2017 in WaM reflects the general trend in Poland and Europe. The decrease of NTS infections in WaM is related to the accession of Poland into the EU., Competing Interests: The authors declare no conflict of interest.

Little is known about the prevalence of persistent human infections by nontyphoidal Salmonella (NTS). Recently published study results indicate that a small fraction (at least 2.2%) of NTS-infected patients continue to shed Salmonella for an extended period of time (up to years). Despite the recommendation not to use antibiotics for the treatment of uncomplicated NTS-Salmonella infection, little treatment guidance is available. Clinical findings from a NTS-patient indicate that administration of synbiotics (probiotic bacteria plus prebiotic) might be considered as a treatment option. We report data of a patient who was treated with a synbiotic preparation containing nine different probiotic bacteria and the prebiotic fructooligosaccharides (FOS). Starting from day one of the treatment, the patient experienced an improvement of symptoms and was symptom-free at the end of a 10 days treatment course. After finishing the treatment, the stool proved to be Salmonella enterica serovar Typhimurium negative. In vitro pathogenic inhibition studies showed the inhibitory effects of the multistrain synbiotic mixture against S. Typhimurium. Growth of S. Typhimurium was also inhibited by individual bacterial strains making part of the composition of the mixture. However, he inhibitory effects of individual strains varied significantly, with those of Streptococcus thermophilus St-21 and Lactobacillus helveticus SP-27 exhibiting the strongest inhibitory effect. Persistent infections by S. Typhimurium are a severe concern for the affected patients. Besides the symptomatic burden, infected persons are banned from work in certain areas (e.g. food related service). In addition, patients with persistent S. Typhimurium infections are a threat for the public health in general, as they serve as a reservoir for NTS transmission. The findings indicate that treatment with a synbiotic preparation might provide a treatment option for persistent S. Typhimurium infections. More clinical data have to be gathered to confirm the relevance of this potential treatment approach.

Salmonella are causes of livestock, poultry, and other animal diseases but they also have the potential to infect people. Currently, antibiotics are the first choice for treatment of Salmonella infections. Thus, the utility of phage has become the research focus for scientists for several reasons. There are efficient, non-toxic, ubiquitous, easy to prepare and can result in the lysis of host bacteria. In this study, a broad spectrum bacteriophage of Salmonella was isolated from the fecal samples of a poultryfarm and we studied the morphological aspects, thermal stability, pH stability, optimal multiplicity of infection (MOI), and one-step growth curve of this phage. This phage was named Salmonella phage SaFB14 and lysed 54.12%(105/194)Salmonella spp. SaFB14 belongs to the Siphoviridae and has a polyhedron head with a diameter approximating 60 × 60 nm and a tail approximating 140 nm. The optimum growth temperature was 37 °C and maintained high activity over a widepH range(pH3-10) with an optimum of pH 7.0. The optimal MOI was 0.1. A one-step growth curve showed that its latency time was 10 min, burst time was 70 min, and burst was 23 particles. In order to study the therapeutic effect of phage SaFB14 in infected mice, mice were challenged with 2 × 10 9  CFU/mouse Salmonella (cs20130523-001-1). Each mouse was injected to 2 × 10 10  PFU SaFB14 1 h later. SaFB14 protected 40% of mice from infection. Then, the same dose of phage was given to mice for 3 days continuously. After 3 days treatment, the survival rate increased to 60%.In conclusion, phage SaFB14 showed wide host range and good activity in vivo, it is promising against diseases caused by Salmonella., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Secretory immunoglobulins have a critical role in defense of the gastrointestinal tract and are known to act by preventing bacterial acquisition. A stringent murine model of bacterial infection with Salmonella enterica Typhimurium was used to examine protection mediated by oral passive immunization with human plasma-derived polyreactive IgA and IgM antibodies (Abs) reconstituted as secretory-like immunoglobulins (SCIgA/M). This reagent has been shown to trigger Salmonella agglutination and to limit the entry of bacterium into intestinal Peyer's patches via immune exclusion. We now demonstrate that upon administration into ligated intestinal loops, SCIgA/M properly anchors in the mucus and is protected from degradation to a better extent that IgA/M or IgG. Moreover, prophylactic oral administration of SCIgA/M before intragastric infection of mice with a virulent strain of S. enterica Typhimurium allows to protect infected animals, as reflected by reduced colonization of both mucosal and systemic compartments, and conserved integrity of intestinal tissues. In comparison with IgA/M or IgG administration, SCIgA/M provided the highest degree of protection. Moreover, such protective efficacy is also observed after therapeutic oral delivery of SCIgA/M. Either prophylactic or therapeutic treatment with passively delivered SCIgA/M ensured survival of up to 50% of infected mice, while untreated animals all died. Our findings unravel the potential of oral passive immunization with plasma-derived polyreactive SCIgA/M Abs to fight gastrointestinal infections.

A Salmonella specific bacteriophage Felix O1 (Myoviridae) was microencapsulated in a pH responsive polymer formulation. The formulation incorporated a pH responsive methacrylic acid copolymer Eudragit® S100 (10% (w/v)) with the addition of the biopolymer sodium alginate, the composition of which was varied in the range (0.5% (w/v)-2% (w/v)). The microencapsulation process employed commercially available microfluidic droplet generation devices. We have used readily available low cost microfluidic chips instead of bespoke in-house fabricated glass capillary devices which are accessible only in specialist research facilities. We show that these co-flow microfluidic devices can easily be used to prepare phage encapsulated microparticles making them suitable for use by both the phage research community and industry in order to evaluate and optimise phage compatible formulations for microencapsulation. A novelty of the work reported here is that the size of the generated monodispersed droplets could be precisely controlled in the range 50 μm-200 μm by varying the flow rates of the dispersed and continuous phases. Consequently, alginate concentration and microparticle size were shown to influence the phage release profile and the degree of acid protection afforded to phages upon exposure to simulated gastric fluid (SGF). Bigger microparticles (∼100 μm) showed better acid protection compared with smaller beads (∼50 μm) made from the same formulation. Increasing the alginate composition resulted in improved acid protection of phages for similar particle sizes. The high viscosity formulations containing higher amounts of alginate (e.g. 2% (w/v)) negatively affected ease of droplet generation in the microfluidic device thereby posing a limitation in terms of process scale-up. Felix O1 encapsulated in the formulation containing 10% (w/v) ES100 and 1% (w/v) alginate showed excellent protection upon exposure of the gelled microparticles to SGF (pH 1 for 2 h) without the use of any antacids in the encapsulation matrix. Encapsulated phages previously exposed to SGF (pH 1 for 2 h) were released at elevated pH in simulated intestinal fluid (SIF) and were shown to arrest bacterial growth in the log growth phase. We have therefore demonstrated the microencapsulation of phages using readily available microfluidic chips to produce solid dosage microcapsule forms with a rapid pH triggered release profile suitable for targeted delivery and controlled release in the gastrointestinal tract., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Brain abscess is a potentially life-threatening condition requiring rapid diagnosis and prompt medical and surgical intervention. Various etiological agents associated with different epidemiological backgrounds are implicated, including Gram-positive and Gram- negative bacterial agents as well as anaerobes. Salmonella is rarely reported to be the cause of this medical condition despite being known to cause invasive infections at extremes of age and the fact that this organism is a common cause of other clinical infectious diseases encountered in immunocompromised and immunocompetent individuals. A case of Salmonella brain abscess involving the right posterior parietal region of the brain is described in a 6-month-old infant. The clinical, microbiological, and radiological features, as well as the clinical management and outcome, are presented. This case highlights the slow-progression nature of brain abscess caused by Salmonella species and the challenge in achieving optimal resolution despite initial surgical intervention.

Prosthetic joint infection due to Salmonella spp is rare. Here we report an acute case of Salmonella enteritidis infection of a total hip arthroplasty in a man taking immunosuppressant medication. He was managed with antibiotics and two-stage revision surgery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Infectious diseases are a common problem in people who travel to countries with poor hygiene standards. Pregnant travellers are subjected to increased risk because of the higher probability of complications in case of certain infectious diseases and the variability of prenatal care quality in these countries., Case Description: A pregnant patient presented herself at the emergency department with recurring fever and chills, a month after she had been to Indonesia. This was associated with a Salmonella infection; the placenta was the infection reservoir., Conclusion: Travelling while pregnant is not without risk. Quick diagnosis and treatment of infections, which may sometimes have an atypical presentation during pregnancy, can be of crucial importance. It is extra important for pregnant people to get travel advice before the trip, so that risks, alarming symptoms and additional hygiene measures can be discussed.

The broad-spectrum lytic capability of Salmonella bacteriophages against various Salmonella species was evaluated to determine their potential as an alternative for antibiotics, and the safety and preventive effects of the bacteriophages were assessed on mice and pigs. Four bacteriophage cocktails were prepared using 13 bacteriophages, and the lytic capability of the four bacteriophage cocktails was tested using Salmonella reference strains and field isolates. Bacteriophage cocktail C (SEP-1, SGP-1, STP-1, SS3eP-1, STP-2, SChP-1, SAP-1, SAP-2; ≥10 9 pfu/ml) showed the best lytic activity against the Salmonella reference strains (100% of 34) and field isolates (92.5% of 107). Fifty mice were then orally inoculated with bacteriophage cocktail C to determine the distribution of bacteriophages in various organs, blood and feces. The effects of bacteriophages on Salmonella infection in weaned pigs (n=15) were also evaluated through an experimental challenge with Salmonella Typhimurium after treatment with bacteriophage cocktail C. All mice exhibited distribution of the bacteriophages in all organs, blood and feces until 15 days post infection (dpi). After 35 dpi, bacteriophages were not detected in any of these specimens. As demonstrated in a pig challenge study, treatment with bacteriophage cocktail C reduced the level of Salmonella shedding in feces. The metagenomic analyses of these pig feces also revealed that bacteriophage treatment decreased the number of species of the Enterobacteriaceae family without significant disturbance to the normal fecal flora. This study showed that bacteriophages effectively controlled Salmonella in a pig challenge model and could be a good alternative for antibiotics to control Salmonella infection.

Multidrug-resistant Salmonella causing Salmonellosis is a food-borne pathogen and hence a public health hazard. Alternatives to antibiotics, such as phages, are possible solutions to this increasing drug resistance. In this context, several Salmonella phages were isolated and characterized. This paper describes the physiochemical and whole genome characterization of one such bacteriophage, ΦStp1, which efficiently infects serovars Salmonella Enteritidis and Salmonella Typhimurium. Morphological observations by transmission electron microscopy and phylogenetic analysis using terminase gene classified ΦStp1 to family Siphoviridae, closely resembling 'T5 like phage' morpho-types. With a maximum adsorption time of 50 min, ΦStp1 latent period was 30 min with 37 phages/cell burst size. ΦStp1 draft genome sequenced by shotgun method comprised 112,149 bp in 3 contigs with 37.99% GC content, 168 predicted ORFs, and 15 tRNAs. Genes involved in host shut down, DNA replication, regulation, nucleotide metabolism, lysis, and morphogenesis were also noted. The study not only provided an insight into the characteristics of phage genome, but also information about proteins encoded by bacteriophages, therefore contributing to understanding phage diversity. Sequence analysis also proved the absence of virulence and lysogeny-related genes, which only went to confirm ΦStp1 as a promising therapeutic agent against Salmonella infections.

Infected or mycotic aneurysms (MAs) of the aorta and adjacent arteries are rare and difficult to treat. We report a unique case of a Salmonella serotype enteritidis-induced rapidly expanding aortic and iliac pseudoaneurysm during preoperative workup. Based on the presented case, we postulate that the agressive nature of Salmonella enteritidis MAs should not be underestimated. If postponed intervention is chosen and the patient is managed conservatively with antibiotic therapy to create a window of definitive diagnosis, one should consider close follow-up imaging to observe progression of the pseudoaneurysm. This may prevent the need of acute intervention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Although purified and synthesized Cecropin A-magainin 2 (CAMA-syn) shows potent antibacterial activity in vitro, its ability to inhibit bacteria within mammal cells mediated by virus vector has not yet been investigated. To enhance its antimicrobial potential and reduce systemic side effects, it would be desirable to deliver CAMA-syn in macrophages by adenovirus vector. In this study,recombinant adenovirus Ad-MSP-CAMA/GFP were used to infect macrophages RAW264.7 cells in vitro and macrophages cells of lungs in vivo and the expression of CAMA-syn was detected by RT-PCR and observation of co-expression of GFP. Antimicrobial activity in cells was evaluated by colony enumeration. The results showed that expression of CAMA-syn in macrophages conferred antimicrobial activity against a series of bacteria, including E. coli and BCG(Bacillus Calmette-Guérin). To establish BCG infection animal model, 40 Kunming mice were randomly divided into the following four groups: adenoviral delivery of Ad-MSP-CAMA/GFP, Ad-CMV-CAMA/GFP, empty-virus Ad-GFP, and control PBS, respectively. The expression of CAMA-syn in mouse was confirmed by real-time PCR and GFP co-expression. In brief, 3 days after injection of adenoviral vector, mice were scarified, different tissues were sectioned and homogenized and colony-forming efficiency by these treated tissues was determined. The colony-forming efficiency of Ad-MSP-CAMA/GFP (78.31%) and Ad-CMV-CAMA/GFP (61.68%) showed significant reduction compared to control groups. No inhibition of bacterial colony was observed from tissues treated by the PBS or empty-virus control. In conclusion, our results demonstrated that macrophages-specific expression of antimicrobial peptide CAMA-syn in macrophages inhibited the growth of intracellular bacteria, providing a promise approach for the control of refractory intracellular infection., (Copyright © 2017. Published by Elsevier B.V.)

This case describes a rare salmonella infection suspected to be an osseous lymphoma. A 27-year-old female presented herself with painful swelling of her knee, with prednisolone-treated Crohn's disease as her only pre-existing condition. Salmonella species group C were detected in the osseous material derived from an extraction. The disease was treated with intravenous ceftriaxone, oral cotrimoxazole as well as multiple debridements. The working diagnosis should thus always be questioned and bone pain in patients who are immunosuppressed should be further investigated.

The indigenous microbiota is the population of microorganisms normally present on the surface and mucosa of an individual, where it performs essential health functions, including the colonisation resistance (CR) against pathogens. To identify the bacteria responsible and the mechanisms involved in the CR, the germ-free (GF) animal model has been used, because in vitro studies cannot always be extrapolated to what occurs in vivo. In this study, ex vivo antagonism assays against seven enteropathogenic bacteria using stools from 15 healthy human donors confirmed that the CR showed individual variation. Using in vitro antagonism assays, 14 strains isolated from dominant faecal microbiota of donors with elevated CR were selected for mono-association in GF mice to test the in vivo antagonism against Salmonella enterica ser. Typhimurium. Mice mono-associated with Enterococcus hirae strain 8.2, Bacteroides thetaiotaomicron strain 16.2 and Lactobacillus ruminis strain 18.1 had significant reductions in faecal counts of the pathogen during the challenge. After five days of infection, the group associated with E. hirae 8.2 showed a reduction in the translocation of S. Typhimurium to the spleen, while the group associated with L. ruminis 18.1 presented an increased translocation to the liver. The histological data confirmed these results and revealed that the mice associated with E. hirae 8.2 showed fewer lesions on ileum and liver, compared to the damage caused by S. Typhimurium alone, while in mice associated with L. ruminis 18.1 there was significantly worse lesions. Concluding, from the dominant faecal microbiota from healthy human with high CR, through ex vivo, in vitro and in vivo assays, a bacterium was characterised for its high CR potential, being a candidate for probiotic use.

The present study was aimed at determining the activity of aqueous and methanolic extracts of Tinospora cordifolia (AETC and METC) against Salmonella typhimurium . In vitro anti- Salmonella activity of T. cordifolia was determined through the broth dilution and agar well diffusion assays. The immune-stimulating potential of AETC or METC was determined by measuring the cytokine levels in the culture supernatants of treated murine J774 macrophages. Antibacterial activity of AETC or METC was determined by treating S. typhimurium- infected macrophages and BALB/C mice. The toxicity of AETC or METC was determined by measuring the levels of liver inflammation markers aspartate transaminase (AST) and alanine transaminase (ALT) and antioxidant enzymes. Macrophages treated with AETC or METC secreted greater levels of IFN- γ , TNF- α , and IL-1 β . METC showed greater activity against S. typhimurium infection in macrophages and mice as well. Treatment with METC resulted in increased survival and reduced bacterial load in S. typhimurium -infected mice. Moreover, METC or AETC treatment reduced the liver inflammation and rescued the levels of antioxidant enzymes in S. typhimurium -infected mice. The results of the present study suggest that the use of T. cordifolia may act as a double-edged sword in combating salmonellosis.

BACKGROUND Acute transverse myelitis (ATM) is an uncommon and often overlooked complication of certain bacterial and viral infections that can have a rapid onset and result in severe neurological deficits.  CASE REPORT This case report describes a previously healthy 28-year-old woman who presented to the trauma center after developing acute paralysis and paresthesias of all four extremities within the span of hours. The initial presumptive diagnosis was spinal cord contusion due to a fall versus an unknown mechanism of trauma, but eventual laboratory studies revealed Salmonella bacteremia, indicating a probable diagnosis of parainfectious ATM. CONCLUSIONS This case illustrates the importance of considering the diagnosis of parainfectious ATM in patients presenting with acute paralysis with incomplete or unobtainable medical histories., Competing Interests: Conflicts of Interest: None declared

The isolation of potentially probiotic strains and the subsequent study of their properties are very important steps to gain insight in the health benefits ascribed to sugary and milk kefir. The aim of the present study was to characterise fifteen Lactobacillus strains isolated from these beverages by determining some surface properties and their ability to antagonise enterocyte cell damage after Salmonella infection in vitro. Lactobacillus surface properties were determined by hydrophobicity, autoaggregation, and coaggregation assays with Salmonella. In addition, lactobacilli adhesion to Caco-2/TC-7 cells and the effect on Salmonella invasion were evaluated. Finally, the disassembly of F-actin cytoskeleton on intestinal epithelial cells was assayed in vitro when Salmonella infection was performed in the presence of selected Lactobacillus strains. Ten out of the 15 strains showed a high adhesion capacity to Caco-2/TC-7 cells. Most of the strains were hydrophilic and non-autoaggregating. Strains isolated from sugary kefir were non-coaggregating with Salmonella, while strains Lactobacillus paracasei CIDCA 83120, 83121, 83123, 83124, 8339, 83102 isolated from milk kefir were able to coaggregate after 1 h. L. paracasei CIDCA 8339 and Lactobacillus kefiri CIDCA 83102 were able to diminish Salmonella invasion to the enterocytes. An antagonistic effect on cytoskeleton disruption elicited by the pathogen was also demonstrated. Our results suggest that both strains isolated from milk kefir could be considered as appropriate probiotic candidates.

Purpose: To review the records of 24 paediatric patients treated for acute bacterial osteomyelitis., Methods: Records of 14 male and 10 female paediatric patients (mean age, 9.4 years) who underwent medical treatment alone (n=3) or combined with surgery (n=21) for acute bacterial osteomyelitis were reviewed. Medical treatment included use of antibiotics and supportive care. Surgery was indicated when the largest dimension of fluid collection was >1 cm., Results: Of the 24 patients, Staphylococcus aureus was isolated in 18, group-D salmonella in 3, and no organism in 3. The mean time from admission to diagnosis was 1.87 days. For those treated surgically, the mean time from diagnosis to surgery was 1.19 days and the mean time from admission to surgery was 2.86 days. Four patients underwent multiple surgeries, 2 of whom developed chronic osteomyelitis and also had negative culture and delayed surgery by >10 days previously. No other patient had any complications., Conclusion: Early surgical intervention for acute bacterial osteomyelitis in children increased diagnostic yield with cultures. For patients with fluid collection <1 cm in the largest dimension, medical treatment alone was effective. Patients with complications were characterised by negative culture, multiple surgeries, and delayed surgery.

This study determined the effects of chicken egg yolk antibodies (IgY) on immune responses in the intestinal mucosal of mice infected with Salmonella typhimurium. Sixty, 28-day-old mice were divided into 4 groups and treated with streptomycin or sterile water for 2days followed by 1day without treatment. The control group was unchallenged whereas the mice in the other three groups were treated twice with 10(9)CFUmL(-1)S. typhimurium. For the next 3days, control mice continued to receive no treatment whereas the mice in the remaining three groups were orally administered with 20mgmL(-1) of specific IgY, 20mgmL(-1) of nonspecific IgY or PBS. S. typhimurium activated gut-associated lymphoid tissue, increasing the release of IFN-γ and TNF-α in the mucosa and increased the number of activated T-lymphocytes and cytotoxic T-γδ. Specific IgY attenuated the increase in IFN-γ and TNF-α and the decrease in IL-10. S. typhimurium induced mobilization of CD8(+) and CD8(+) TCRγδ T cells in the epithelium and CD4(+) and CD8(+) T cells in the lamina propria reflecting an inflammatory process that was attenuated by IgY. These results suggest that specific IgY modulates intestinal mucosal immune responses during a S. typhimurium infection., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Salmonella enterica is among the most burdensome of foodborne disease agents. There are over 2,600 serovars that cause a range of disease manifestations ranging from enterocolitis to typhoid fever. While there are two vaccines in use in humans to protect against typhoid fever, there are none that prevent enterocolitis. If vaccines preventing enterocolitis were to be developed, they would likely protect against only one or a few serovars. In this report, we tested the hypothesis that probiotic organisms could compete for the preferred nutrient sources of Salmonella and thus prevent or treat infection. To this end, we added the fra locus, which encodes a utilization pathway for the Salmonella-specific nutrient source fructose-asparagine (F-Asn), to the probiotic bacterium Escherichia coli Nissle 1917 (Nissle) to increase its ability to compete with Salmonella in mouse models. We also tested a metabolically competent, but avirulent, Salmonella enterica serovar Typhimurium mutant for its ability to compete with wild-type Salmonella The modified Nissle strain became more virulent and less able to protect against Salmonella in some instances. On the other hand, the modified Salmonella strain was safe and effective in preventing infection with wild-type Salmonella While we tested for efficacy only against Salmonella Typhimurium, the modified Salmonella strain may be able to compete metabolically with most, if not all, Salmonella serovars, representing a novel approach to control of this pathogen., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)