scholarly journals Understanding and exploiting the response of EHEC O157:H7 to human gastrointestinal chemical signals

2021 ◽  
Author(s):  
Tracy Linda Brittney Lackraj
Keyword(s):  
Antimicrobial Peptide ◽  
Large Intestine ◽  
Foodborne Pathogen ◽  
Acid Stress ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Susceptibility ◽  
Gi Tract ◽  
Cationic Antimicrobial Peptide ◽  
Susceptibility To Infection ◽  
Commensal Flora

Enterohemorrhagic Escherichia coli (EHEC) is a clinically relevant foodborne pathogen, resulting in over 95,000 cases of EHEC-associated illness and 60 deaths each year in the US alone. Since EHEC is a continuous global issue with new outbreaks constantly occurring, the development of new therapeutic strategies is vital to minimizing the cases of infection seen each year. A key aspect in new drug development is the identification of vulnerabilities in EHEC’s pathogenicity, in particular, during its transit through the human gastrointestinal (GI) tract. As EHEC passes through the human GI tract to its site of colonization in the large intestine, it faces a multitude of host assaults including acute acid stress in the stomach, bile salt stress and cationic antimicrobial peptide exposure in the small intestine, and short chain fatty acid (SCFA) stress in the large intestine. The research carried out in this doctoral dissertation focuses on understanding how EHEC senses chemical cues from the host’s innate immune responses and how this knowledge can be exploited to develop effective antimicrobial strategies. Our findings successfully demonstrate that a novel antimicrobial peptide ameliorates infection in a mouse model of infection by enhancing acid-induced pathogen killing during gastric passage, and that the DNAbinding protein, Dps, plays a significant role in protecting EHEC against peptide killing. Moreover, this research successfully shows that varying concentrations of SCFAs result in differential modulation of EHEC virulence – a finding that contributes to our understanding of the role of diet and commensal flora in host susceptibility to infection. Together the findings of this research demonstrate how the selected innate host defences throughout the human GI tract can be exploited and/or manipulated to effectively prevent infection by the human pathogen EHEC.

scholarly journals Understanding and exploiting the response of EHEC O157:H7 to human gastrointestinal chemical signals

2021 ◽  
Author(s):  
Tracy Linda Brittney Lackraj
Keyword(s):  
Antimicrobial Peptide ◽  
Large Intestine ◽  
Foodborne Pathogen ◽  
Acid Stress ◽  
Enterohemorrhagic Escherichia Coli ◽  
Host Susceptibility ◽  
Gi Tract ◽  
Cationic Antimicrobial Peptide ◽  
Susceptibility To Infection ◽  
Commensal Flora

Enterohemorrhagic Escherichia coli (EHEC) is a clinically relevant foodborne pathogen, resulting in over 95,000 cases of EHEC-associated illness and 60 deaths each year in the US alone. Since EHEC is a continuous global issue with new outbreaks constantly occurring, the development of new therapeutic strategies is vital to minimizing the cases of infection seen each year. A key aspect in new drug development is the identification of vulnerabilities in EHEC’s pathogenicity, in particular, during its transit through the human gastrointestinal (GI) tract. As EHEC passes through the human GI tract to its site of colonization in the large intestine, it faces a multitude of host assaults including acute acid stress in the stomach, bile salt stress and cationic antimicrobial peptide exposure in the small intestine, and short chain fatty acid (SCFA) stress in the large intestine. The research carried out in this doctoral dissertation focuses on understanding how EHEC senses chemical cues from the host’s innate immune responses and how this knowledge can be exploited to develop effective antimicrobial strategies. Our findings successfully demonstrate that a novel antimicrobial peptide ameliorates infection in a mouse model of infection by enhancing acid-induced pathogen killing during gastric passage, and that the DNAbinding protein, Dps, plays a significant role in protecting EHEC against peptide killing. Moreover, this research successfully shows that varying concentrations of SCFAs result in differential modulation of EHEC virulence – a finding that contributes to our understanding of the role of diet and commensal flora in host susceptibility to infection. Together the findings of this research demonstrate how the selected innate host defences throughout the human GI tract can be exploited and/or manipulated to effectively prevent infection by the human pathogen EHEC.

Intestinal microbiota balance modulates host susceptibility to infection with enteric pathogenss

2007 ◽  
Vol 30 (4) ◽  
pp. 93
Author(s):  
I Sekirov ◽  
N Tam ◽  
M Robertson ◽  
C Lupp ◽  
B Finlay
Keyword(s):  
Intestinal Microbiota ◽  
Small Animal ◽  
Host Susceptibility ◽  
Morphological Development ◽  
Future Design ◽  
Susceptibility To Infection ◽  
Colonic Microbiota ◽  
Food Borne ◽  
Serovar Typhimurium ◽  
Intestinal Pathogens

Background: During our lifetimes we develop a very complex set of interactions with the multitude of microorganisms colonizing our bodies. In the gastrointestinal system, the microbiota is highly important for morphological development, nutrition, and protection against infectious diseases. The gastrointestinal pathogens, enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) and Salmonella enterica serovar Typhimurium (ST) are food-borne pathogens that cause much morbidity and mortality worldwide. Citrobacter rodentium (Cr) is a mouse pathogen that is used in small animal models to mimic EHEC and EPEC infections. Methods: We began to characterize the contribution of intestinal microbiota to the progression of these infections. Two main phyla comprise the majority of mouse intestinal microbiota: Bacteroidetes and Firmicutes. Bacteria from a number of additional phyla are also present in smaller numbers; among them γ-Proteobacteria class, belonging to Proteobacteria phylum, is note-worthy as this class harbours many intestinal pathogens, such as ST and Cr. The mouse intestinal microbiota was perturbed using tetracycline (Tet) and streptomycin (Sm) to increase the proportion of Bacteroidetes in the colonic microbiota, and using vancomycin (Vanc) to create a predominance of Firmicutes. The mice with this perturbed microbiota were infected with ST to investigate the resultant pathology and virulence characteristics, and any additional shifts in microbiota as a result of infection. Results: Treatment of mice with Sm and Vanc was found to decrease the resistance of mice to colonization with ST, while Tet-treated mice exhibited unchanged colonization resistance. Treatment of mice with gradually increasing doses of Sm, which gradually augmented the proportion of CFB bacteria in the microbiota, resulted in progressively increasing colonization of mice by ST, as well as a step-wise increase in the ST-induced typhlitis, associated with higher levels of inflammatory markers IL-6 and KC. The increasing levels of ST colonization following both Sm and Vanc treatment were associated with an increase in the proportion of γ-Proteobacteria in the cecal and colonic microbiota, as well as a decrease in the total bacterial numbers in both organs. Conclusions: It is evident that the intestinal microbiota plays a significant role in the host’s response to infection with enteric pathogens, and its composition and numbers are also affected by the offending bacteria. Elucidation of the details regarding the contribution of the microbiota to infectious disease progression will offer novel targets for the future design of superior prevention and treatment methods.

Highly efficient nanomedicine from cationic antimicrobial peptide-protected Ag nanoclusters

2021 ◽  
Author(s):  
Zhikai Ye ◽  
Haishuang Zhu ◽  
Shan Zhang ◽  
Jing Li ◽  
Jin Wang ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Biological Systems ◽  
Cationic Antimicrobial Peptide ◽  
Highly Efficient ◽  
Antimicrobial Efficiency ◽  
Ag Nanoclusters ◽  
Fine Tune

Designing the homogeneous assembly of the bio–nano interface to fine-tune the interactions between the nanoprobes and biological systems is of prime importance to improve the antimicrobial efficiency of nanomedicines.

scholarly journals Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

2021 ◽  
Vol 22 (6) ◽  
pp. 2857
Author(s):  
Filomena Battista ◽  
Rosario Oliva ◽  
Pompea Del Vecchio ◽  
Roland Winter ◽  
Luigi Petraccone
Keyword(s):  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Lipid Domains ◽  
Action Mechanism ◽  
Cationic Antimicrobial Peptide ◽  
Intracellular Targeting ◽  
Gel Retardation Assay ◽  
Charged Membrane ◽  
Intracellular Target ◽  
Anionic Lipids

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.

scholarly journals Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties

2022 ◽  
Vol 1249 ◽  
pp. 131482
Author(s):  
Mina Răileanu ◽  
Barbara Lonetti ◽  
Charles-Louis Serpentini ◽  
Dominique Goudounèche ◽  
Laure Gibot ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Cationic Antimicrobial Peptide ◽  
Polyion Complex ◽  
Antitumor Properties ◽  
Self Assembled

Spermicidal efficacy of VRP, a synthetic cationic antimicrobial peptide, inducing apoptosis and membrane disruption

2017 ◽  
Vol 233 (2) ◽  
pp. 1041-1050 ◽  
Author(s):  
Prasanta Ghosh ◽  
Arpita Bhoumik ◽  
Sudipta Saha ◽  
Sandipan Mukherjee ◽  
Sarfuddin Azmi ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Membrane Disruption ◽  
Cationic Antimicrobial Peptide

Explaining variability in parasite aggregation levels among host samples

Parasitology ◽  
2013 ◽  
Vol 140 (4) ◽  
pp. 541-546 ◽  
Author(s):  
ROBERT POULIN
Keyword(s):  
Body Size ◽  
Strong Relationship ◽  
Host Susceptibility ◽  
Helminth Parasites ◽  
Susceptibility To Infection ◽  
Host Body ◽  
Parasite Aggregation ◽  
Using Data ◽  
Species Specific ◽  
Host Body Size

SUMMARYAggregated distributions among individual hosts are a defining feature of metazoan parasite populations. Heterogeneity among host individuals in exposure to parasites or in susceptibility to infection is thought to be the main factor generating aggregation, with properties of parasites themselves explaining some of the variability in aggregation levels observed among species. Here, using data from 410 samples of helminth parasites on fish hosts, I tested the contribution of (i) within-sample variation in host body size, taken as a proxy for variability in host susceptibility, and (ii) parasite taxon and developmental stage, to the aggregated distribution of parasites. Log-transformed variance in numbers of parasites per host was regressed against log mean number across all samples; the strong relationship (r2 = 0·88) indicated that aggregation levels are tightly constrained by mean infection levels, and that only a small proportion of the observed variability in parasite aggregation levels remains to be accounted for by other factors. Using the residuals of this regression as measures of ‘unexplained’ aggregation, a mixed effects model revealed no significant effect of within-sample variation in host body size or of parasite taxon or stage (i.e. juvenile versus adult) on parasite aggregation level within a sample. However, much of the remaining variability in parasite aggregation levels among samples was accounted for by the number of individual hosts examined per sample, and species-specific and study-specific effects reflecting idiosyncrasies of particular systems. This suggests that with most differences in aggregation among samples already explained, there may be little point in seeking universal causes for the remaining variation.

scholarly journals Interaction of Escherichia coli O157:H7 with Leafy Green Produce

2009 ◽  
Vol 72 (7) ◽  
pp. 1531-1537 ◽  
Author(s):  
JUAN XICOHTENCATL-CORTES ◽  
ETHEL SÁNCHEZ CHACÓN ◽  
ZEUS SALDAÑA ◽  
ENRIQUE FREER ◽  
JORGE A. GIRÓN
Keyword(s):  
Escherichia Coli ◽  
Diarrheal Disease ◽  
Foodborne Pathogen ◽  
Enterohemorrhagic Escherichia Coli ◽  
Animal Products ◽  
Atpase Gene ◽  
Type 3 Secretion System ◽  
Human Infections ◽  
Type 3

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen responsible for human diarrheal disease. EHEC lives in the intestinal tract of cattle and other farm and wild animals, which may be the source of environmental contamination particularly of agricultural fields. Human infections are associated with consumption of tainted animal products and fresh produce. How the bacteria interact with the plant phyllosphere and withstand industrial decontamination remain to be elucidated. The goals of the present study were to investigate the environmental conditions and surface structures that influence the interaction of EHEC O157:H7 with baby spinach and lettuce leaves in vitro. Independently of the production of Shiga toxin, EHEC O157:H7 colonizes the leaf surface via flagella and the type 3 secretion system (T3SS). Ultrastructural analysis of EHEC-infected leafy greens revealed the presence of flagellated bacteria, and mutation of the fliC flagellin gene in EHEC EDL933 rendered the bacteria significantly less adherent, suggesting the involvement of flagella in the bacteria-leaf interaction. EDL933 mutated in the escN (ATPase) gene associated with the function of the T3SS but not in the eae (intimin adhesin) gene required for adherence to host intestinal cells had significantly reduced adherence compared with that of the parental strain. The data suggest a compelling role of flagella and the T3SS in colonization of leafy green produce. Colonization of salad leaves by EHEC strains may be a strategy that ensures survival of these bacteria in the environment and allows transmission to the human host.

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