scholarly journals Investigation of Salmonella Phage–Bacteria Infection Profiles: Network Structure Reveals a Gradient of Target-Range from Generalist to Specialist Phage Clones in Nested Subsets

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1261
Author(s):  
Khatuna Makalatia ◽  
Elene Kakabadze ◽  
Nata Bakuradze ◽  
Nino Grdzelishvili ◽  
Ben Stamp ◽  
...  
Keyword(s):  
Host Range ◽  
Salmonella Enterica ◽  
Target Range ◽  
Nested Subsets ◽  
Specific Phage ◽  
Salmonella Infections ◽  
Specialist Species ◽  
Host Infection ◽  
Salmonella Phage

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.

scholarly journals Cytokine-Mediated Regulation of ARG1 in Macrophages and Its Impact on the Control of Salmonella enterica Serovar Typhimurium Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1823
Author(s):  
Natascha Brigo ◽  
Christa Pfeifhofer-Obermair ◽  
Piotr Tymoszuk ◽  
Egon Demetz ◽  
Sabine Engl ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Natural Resistance ◽  
Bacterial Survival ◽  
Wild Type ◽  
Salmonella Infections ◽  
Arginase 1 ◽  
Serovar Typhimurium ◽  
The Impact

Arginase 1 (ARG1) is a cytosolic enzyme that cleaves L-arginine, the substrate of inducible nitric oxide synthase (iNOS), and thereby impairs the control of various intracellular pathogens. Herein, we investigated the role of ARG1 during infection with Salmonella enterica serovar Typhimurium (S.tm). To study the impact of ARG1 on Salmonella infections in vitro, bone marrow-derived macrophages (BMDM) from C57BL/6N wild-type, ARG1-deficient Tie2Cre+/−ARG1fl/fl and NRAMPG169 C57BL/6N mice were infected with S.tm. In wild-type BMDM, ARG1 was induced by S.tm and further upregulated by the addition of interleukin (IL)-4, whereas interferon-γ had an inhibitory effect. Deletion of ARG1 did not result in a reduction in bacterial numbers. In vivo, Arg1 mRNA was upregulated in the spleen, but not in the liver of C57BL/6N mice following intraperitoneal S.tm infection. The genetic deletion of ARG1 (Tie2Cre+/−ARG1fl/fl) or its pharmacological inhibition with CB-1158 neither affected the numbers of S.tm in spleen, liver and blood nor the expression of host response genes such as iNOS, IL-6 or tumour necrosis factor (TNF). Furthermore, ARG1 was dispensable for pathogen control irrespective of the presence or absence of the phagolysosomal natural resistance-associated macrophage protein 1 (NRAMP1). Thus, unlike the detrimental function of ARG1 seen during infections with other intraphagosomal microorganisms, ARG1 did not support bacterial survival in systemic salmonellosis, indicating differential roles of arginine metabolism for host immune response and microbe persistence depending on the type of pathogen.

scholarly journals Phage Therapy To Reduce Preprocessing Salmonella Infections in Market-Weight Swine

2009 ◽  
Vol 76 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Samantha K. Wall ◽  
Jiayi Zhang ◽  
Marcos H. Rostagno ◽  
Paul D. Ebner
Keyword(s):  
Salmonella Enterica ◽  
Phage Therapy ◽  
Meat Products ◽  
Log Reduction ◽  
Salmonella Infections ◽  
Food Borne ◽  
Phage Cocktail ◽  
Serovar Typhimurium ◽  
Mock Treatment

ABSTRACT Contamination of meat products with food-borne pathogens usually results from the carcass coming in contact with the feces of an infected animal during processing. In the case of Salmonella, pigs can become colonized with the organism during transport and lairage from contaminated trailers and holding pens, resulting in increased pathogen shedding just prior to processing. Increased shedding, in turn, amplifies the likelihood of carcass contamination by magnifying the amount of bacteria that enters the processing facility. We conducted a series of experiments to test whether phage therapy could limit Salmonella infections at this crucial period. In a preliminary experiment done with small pigs (3 to 4 weeks old; 30 to 40 lb), administration of an anti-Salmonella phage cocktail at the time of inoculation with Salmonella enterica serovar Typhimurium reduced Salmonella colonization by 99.0 to 99.9% (2- to 3-log reduction) in the tonsils, ileum, and cecum. To test the efficacy of phage therapy in a production-like setting, we inoculated four market-weight pigs (in three replicates) with Salmonella enterica serovar Typhimurium and allowed the challenged pigs to contaminate a holding pen for 48 h. Sixteen naïve pigs were randomly split into two groups which received either the anti-Salmonella phage cocktail or a mock treatment. Both groups of pigs were comingled with the challenged pigs in the contaminated pen. Treatment with the anti-Salmonella phage cocktail significantly reduced cecal Salmonella concentrations (95%; P < 0.05) while also reducing (numerically) ileal Salmonella concentrations (90%; P = 0.06). Additional in vitro studies showed that the phage cocktail was also lytic against several non-Typhimurium serovars.

scholarly journals Efficiency of Single Phage Suspensions and Phage Cocktail in the Inactivation of Escherichia coli and Salmonella Typhimurium: An In Vitro Preliminary Study

2019 ◽  
Vol 7 (4) ◽  
pp. 94 ◽  
Author(s):  
Pedro Costa ◽  
Carla Pereira ◽  
Ana Gomes ◽  
Adelaide Almeida
Keyword(s):  
Escherichia Coli ◽  
Action Spectrum ◽  
E Coli ◽  
Specific Phage ◽  
Salmonella Infections ◽  
Serovar Typhimurium ◽  
Resistant Mutants ◽  
Community Environments ◽  
Enterobacteriaceae Infections

Enterobacteriaceae Escherichia coli and Salmonella enterica serovar Typhimurium strains are among the main pathogens responsible for moderate and serious infections at hospital and community environments, in part because they frequently present resistance to antibiotics. As the treatment of Enterobacteriaceae infections is empiric, using the same antibiotics to treat E. coli and Salmonella infections, the same concept can be applied with phages. The use of different phages combined in cocktails, frequently used to circumvent the development of phage-resistant mutants, also allows for the treatment of multiple pathogens, broadening the phages’ action spectrum. As such, the aim of this study was to evaluate the efficiency of a cocktail of two phages (ELY-1, produced on E. coli and phSE-5, produced on S. Typhimurium) to control E. coli and S. Typhimurium. Phages ELY-1 and phSE-5 were effective against E. coli (maximum reductions of 4.5 and 3.8 log CFU/mL, respectively), S. Typhimurium (maximum reductions of 2.2 and 2.6 log CFU/mL, respectively), and the mixture of both bacteria (maximum reductions of 2.2 and 2.0 log CFU/mL, respectively). The cocktail ELY-1/phSE-5 was more effective against S. Typhimurium and the mixture of both bacteria (maximum reduction of 3.2 log CFU/mL for both) than the single phage suspensions and as effective against E. coli as its specific phage ELY-1 (maximum reductions of 4.5 log CFU/mL). The use of both the phage cocktails, as well as the single-phage suspensions, however, did not prevent the occurrence of phage-resistant mutants. Overall, the results indicate that the application of the phages in the form of a cocktail show their potential to be used presumptively, that is, prior to the identification of the pathogens, paving its use to control E. coli or S. Typhimurium.

scholarly journals Morphology of Salmonella Typhimurium typing phages of the Lilleengen set

2009 ◽  
Vol 55 (12) ◽  
pp. 1403-1405 ◽  
Author(s):  
Abraham Eisenstark ◽  
Wolfgang Rabsch ◽  
Hans-W. Ackermann
Keyword(s):  
Salmonella Typhimurium ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Specific Phage ◽  
Serovar Typhimurium ◽  
Phage P22 ◽  
Salmonella Phage

The Lilleengen scheme for typing Salmonella enterica serovar Typhimurium consists of 12 tailed phages. Ten phages are podoviruses and morphologically identical to Salmonella phage P22. Two phages are siphoviruses and identical to flagella-specific phage χ.

scholarly journals Revealing biophysical properties of KfrA-type proteins as a novel class of cytoskeletal, coiled-coil plasmid-encoded proteins

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Adamczyk ◽  
E. Lewicka ◽  
R. Szatkowska ◽  
H. Nieznanska ◽  
J. Ludwiczak ◽  
...  
Keyword(s):  
Dna Binding ◽  
Host Range ◽  
Coiled Coil ◽  
Amino Acid Sequences ◽  
Broad Host Range ◽  
Biophysical Properties ◽  
Dna Binding Sites ◽  
In Silico Studies ◽  
Wide Range

Abstract Background DNA binding KfrA-type proteins of broad-host-range bacterial plasmids belonging to IncP-1 and IncU incompatibility groups are characterized by globular N-terminal head domains and long alpha-helical coiled-coil tails. They have been shown to act as transcriptional auto-regulators. Results This study was focused on two members of the growing family of KfrA-type proteins encoded by the broad-host-range plasmids, R751 of IncP-1β and RA3 of IncU groups. Comparative in vitro and in silico studies on KfrAR751 and KfrARA3 confirmed their similar biophysical properties despite low conservation of the amino acid sequences. They form a wide range of oligomeric forms in vitro and, in the presence of their cognate DNA binding sites, they polymerize into the higher order filaments visualized as “threads” by negative staining electron microscopy. The studies revealed also temperature-dependent changes in the coiled-coil segment of KfrA proteins that is involved in the stabilization of dimers required for DNA interactions. Conclusion KfrAR751 and KfrARA3 are structural homologues. We postulate that KfrA type proteins have moonlighting activity. They not only act as transcriptional auto-regulators but form cytoskeletal structures, which might facilitate plasmid DNA delivery and positioning in the cells before cell division, involving thermal energy.

scholarly journals In Vitro Activity of Azithromycin against Nontyphoidal Salmonella enterica

2010 ◽  
Vol 54 (8) ◽  
pp. 3498-3501 ◽  
Author(s):  
Marianne Gunell ◽  
Pirkko Kotilainen ◽  
Jari Jalava ◽  
Pentti Huovinen ◽  
Anja Siitonen ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Clinical Treatment ◽  
Vitro Activity ◽  
In Vitro Activity

ABSTRACT The in vitro activity of azithromycin against 1,237 nontyphoidal Salmonella enterica isolates collected from Finnish patients between 2003 and 2008 was investigated. Only 24 (1.9%) of the isolates tested and 15 (5.1%) of the 294 isolates with reduced fluoroquinolone susceptibility had azithromycin MICs of ≥32 μg/ml. These data show that azithromycin has good in vitro activity against nontyphoidal S. enterica, and thus, it may be a good candidate for clinical treatment studies of salmonellosis.

Integration host factor alleviates H-NS silencing of the Salmonella enterica serovar Typhimurium master regulator of SPI1, hilA

Microbiology ◽  
2011 ◽  
Vol 157 (9) ◽  
pp. 2504-2514 ◽  
Author(s):  
Mário H. Queiroz ◽  
Cristina Madrid ◽  
Sònia Paytubi ◽  
Carlos Balsalobre ◽  
Antonio Juárez
Keyword(s):  
Stationary Phase ◽  
Salmonella Enterica ◽  
Growth Conditions ◽  
Integration Host Factor ◽  
Band Shift ◽  
Global Regulators ◽  
Serovar Typhimurium ◽  
Associated Proteins ◽  
Transcription Data

Coordination of the expression of Salmonella enterica invasion genes on Salmonella pathogenicity island 1 (SPI1) depends on a complex circuit involving several regulators that converge on expression of the hilA gene, which encodes a transcriptional activator (HilA) that modulates expression of the SPI1 virulence genes. Two of the global regulators that influence hilA expression are the nucleoid-associated proteins Hha and H-NS. They interact and form a complex that modulates gene expression. A chromosomal transcriptional fusion was constructed to assess the effects of these modulators on hilA transcription under several environmental conditions as well as at different stages of growth. The results obtained showed that these proteins play a role in silencing hilA expression at both low temperature and low osmolarity, irrespective of the growth phase. H-NS accounts for the main repressor activity. At high temperature and osmolarity, H-NS-mediated silencing completely ceases when cells enter the stationary phase, and hilA expression is induced. Mutants lacking IHF did not induce hilA in cells entering the stationary phase, and this lack of induction was dependent on the presence of H-NS. Band-shift assays and in vitro transcription data showed that for hilA induction under certain growth conditions, IHF is required to alleviate H-NS-mediated silencing.

scholarly journals Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1141
Author(s):  
Richard M. Beteck ◽  
Audrey Jordaan ◽  
Ronnett Seldon ◽  
Dustin Laming ◽  
Heinrich C. Hoppe ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protozoan Parasites ◽  
Trypanosoma Brucei Brucei ◽  
New Class ◽  
High Lipid ◽  
Host Infection ◽  
Eskape Pathogens ◽  
Quinolone Derivatives ◽  
Lipophilic Character

The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24–31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4–20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.

Biocontrol of seed-borne Alternaria raphani and A. brassicicola

1987 ◽  
Vol 33 (10) ◽  
pp. 850-856 ◽  
Author(s):  
G. Vannacci ◽  
G. E. Harman
Keyword(s):  
Biological Control ◽  
Host Range ◽  
Trichoderma Harzianum ◽  
Pythium Species ◽  
Biological Control Agents ◽  
Fusarium Sp ◽  
Chamber Studies ◽  
Growth Chamber Studies ◽  
Radish Seedlings

Forty-two microorganisms were tested as biological control agents against Alternaria raphani and A. brassicicola. Tests were conducted for in vitro antagonistic ability, for ability to control the pathogens on naturally infected seeds germinated on moistened blotters, and in planting mix in growth chamber studies, and for their ability to reduce pod infection. The organisms tested were obtained from cruciferous seeds or were strains already identified as being effective against soil-borne Pythium species. The blotter test indicated that six organisms increased both the number of healthy seedlings and the number of seedlings produced from A. raphani infected radish seeds. An additional seven strains improved either germination or increased the number of healthy seedlings. Twenty-nine organisms increased the number of healthy cabbage seedlings from A. brassicicola infected seeds, but total germination was not modified by any treatment. Experiments in planting mix showed that five antagonists (Chaetomium globosum, two strains of Trichoderma harzianum, T. koningii, and Fusarium sp.) increased the number of healthy plants in both radish samples tested, while four additional antagonists provided a significant increase in only one of the samples tested. The five antagonists that consistently increased numbers of healthy radish seedlings also decreased pod infection by A. raphani. None were as effective as iprodrone, however. Several effective antagonists were found to be mycoparasitic against Alternaria spp. Some strains of Trichoderma previously found to be effective against Pythium spp. were also effective against Alternaria spp., indicating that these strains have a wide host range.

scholarly journals A Salmonella Virulence Factor Activates the NOD1/NOD2 Signaling Pathway

mBio ◽  
2011 ◽  
Vol 2 (6) ◽  
Author(s):  
A. Marijke Keestra ◽  
Maria G. Winter ◽  
Daisy Klein-Douwel ◽  
Mariana N. Xavier ◽  
Sebastian E. Winter ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Type Iii

ABSTRACTThe invasion-associated type III secretion system (T3SS-1) ofSalmonella entericaserotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expression of SipA, a T3SS-1-translocated protein, led to the activation of the NOD1/NOD2 signaling pathway and consequent RIP2-mediated induction of NF-κB-dependent inflammatory responses. SipA-mediated activation of NOD1/NOD2 signaling was independent of bacterial invasionin vitrobut required an intact T3SS-1. In the mouse colitis model, SipA triggered mucosal inflammation in wild-type mice but not in NOD1/NOD2-deficient mice. These findings implicate SipA-driven activation of the NOD1/NOD2 signaling pathway as a mechanism by which the T3SS-1 induces inflammatory responsesin vitroandin vivo.IMPORTANCESalmonella entericaserotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol.

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