scholarly journals Insights into mucosal innate responses to Escherichia coli O157 : H7 colonization of cattle by mathematical modelling of excretion dynamics

2011 ◽  
Vol 9 (68) ◽  
pp. 518-527 ◽  
Author(s):  
Michael J. Tildesley ◽  
David L. Gally ◽  
Tom N. McNeilly ◽  
J. Chris Low ◽  
Arvind Mahajan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mathematical Model ◽  
Model Comparison ◽  
Innate Immune ◽  
Host Responses ◽  
Post Inoculation ◽  
Model Based ◽  
Complex Interactions ◽  
Bacterial Replication

Mathematical model-based statistical inference applied to within-host dynamics of infectious diseases can help dissect complex interactions between hosts and microbes. This work has applied advances in model-based inference to understand colonization of cattle by enterohaemorrhagic Escherichia coli O157 : H7 at the terminal rectum. A mathematical model was developed based on niche replication and transition rates at this site. A nested-model comparison, applied to excretion curves from 25 calves, was used to reduce complexity while maintaining integrity. We conclude that, 5–9 days post inoculation, the innate immune response negates bacterial replication on the epithelium and either reduces attachment to or increases detachment from the epithelium of the terminal rectum. Thus, we provide a broadly applicable model that gives novel insights into bacterial replication rates in vivo and the timing and impact of host responses.

scholarly journals Enterotoxigenic Escherichia coli Prevents Host NF-κB Activation by Targeting IκBα Polyubiquitination

2012 ◽  
Vol 80 (12) ◽  
pp. 4417-4425 ◽  
Author(s):  
Xiaogang Wang ◽  
Philip R. Hardwidge
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Diarrheal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Enterotoxigenic Escherichia Coli ◽  
Host Responses ◽  
Innate Immune Responses ◽  
Content Type ◽  
Heat Stable

ABSTRACTThe NF-κB pathway regulates innate immune responses to infection. NF-κB is activated after pathogen-associated molecular patterns are detected, leading to the induction of proinflammatory host responses. As a countermeasure, bacterial pathogens have evolved mechanisms to subvert NF-κB signaling. EnterotoxigenicEscherichia coli(ETEC) causes diarrheal disease and significant morbidity and mortality for humans in developing nations. The extent to which this important pathogen subverts innate immune responses by directly targeting the NF-κB pathway is an understudied topic. Here we report that ETEC secretes a heat-stable, proteinaceous factor that blocks NF-κB signaling normally induced by tumor necrosis factor (TNF), interleukin-1β, and flagellin. Pretreating intestinal epithelial cells with ETEC supernatant significantly blocked the degradation of the NF-κB inhibitor IκBα without affecting IκBα phosphorylation. Data from immunoprecipitation experiments suggest that the ETEC factor functions by preventing IκBα polyubiquitination. Inhibiting clathrin function blocked the activity of the secreted ETEC factor, suggesting that this yet-uncharacterized activity may utilize clathrin-dependent endocytosis to enter host cells. These data suggest that ETEC evades the host innate immune response by directly modulating NF-κB signaling.

scholarly journals Dual Protective Functions of Helicobacter pylori Peptidoglycan Modifications Impact Early and Late Survival in the Host

2013 ◽  
Vol 1 (1) ◽  
pp. 1-7
Author(s):  
Ge Wang
Keyword(s):  
Helicobacter Pylori ◽  
Double Mutant ◽  
Host Responses ◽  
Host Recognition ◽  
Post Inoculation ◽  
Wild Type ◽  
Naturally Occurring ◽  
Double Mutant Strain ◽  
H Pylori

Structural motifs inherent in bacterial peptidoglycan (PG) are important recognition domains for some efficient host responses to pathogenic bacterial infection, so PG modifications by the infecting bacterium can neutralize host responses. Helicobacter pylori contain two PG modification enzymes, an N-deacetylase (PgdA) and an O-acetyltransferase (PatAB), but some naturally occurring strains lack the latter. Here the lysozyme resistance and the survival in both macrophages and in lysozyme deficient mice were studied for various H. pylori strains. Resistance to lysozyme killing of H. pylori was conferred by PgdA in naturally-occurring strains that lacked PatA (e.g. B128); the lysozyme sensitivity for B128 pgdA mutant was at the same level as that of a double mutant (pgdA patA) version within parent strain X47. Both PgdA- and PatAmediated PG modifications are important to H. pylori survival within macrophages. Mouse studies connected the lysozyme and macrophage results to the in vivo condition, in which lysozyme effects are expected early and cytokine production later, pertaining to specific host recognition events. An increased host lysozyme killing effect associated with the double mutant strain (pgdA patA) was indicated from a reduced colonization phenotype (compared to wild type) after a week post-inoculation of lysozyme-positive mice; at this time point some important anti- H. pylori mouse cytokines were shown to be minimal. At 3 weeks post-inoculation, the levels of 3 cytokines (IL-10, TNF-a, and MIP-2) were significantly higher in sera of mice inoculated with the pgdApatA strain, and the pgdApatA strain showed a greatly attenuated ability of mouse colonization, in contrast to the wild type strain, indicating a significant role of PG modifications in persistent infection through mitigating host immune response. However, the double mutant survived better in lysozyme deficient (LysM-/-) mice, supporting the notion that PgdA- and PatA- mediated PG modifications in H. pylori protect bacteria from killing by host lysozyme.

scholarly journals The effect of enrofloxacin on enteric Escherichia coli: Fitting a mathematical model to in vivo data

PLoS ONE ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. e0228138
Author(s):  
Samantha Erwin ◽  
Derek M. Foster ◽  
Megan E. Jacob ◽  
Mark G. Papich ◽  
Cristina Lanzas
Keyword(s):  
Escherichia Coli ◽  
Mathematical Model

scholarly journals Waging War against Uropathogenic Escherichia coli: Winning Back the Urinary Tract

2009 ◽  
Vol 78 (2) ◽  
pp. 568-585 ◽  
Author(s):  
Kelsey E. Sivick ◽  
Harry L. T. Mobley
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
The United States ◽  
Innate Immune ◽  
Host Responses ◽  
Public Health Issue ◽  
Innate Immune Responses ◽  
Phagocytic Cells ◽  
Successful Vaccine ◽  
Lost Productivity

ABSTRACT Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden—a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses—from pattern receptor recognition to recruitment of phagocytic cells—that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity.

Zinc oxide inhibits enterotoxigenic Escherichia coli K88 growth in culture and reduces the inflammatory response of porcine intestinal epithelial cells to infection

2009 ◽  
Vol 2009 ◽  
pp. 32-32
Author(s):  
H Sargeant ◽  
M-A Shaw ◽  
H M Miller
Keyword(s):  
Escherichia Coli ◽  
Zinc Oxide ◽  
Intestinal Epithelial Cells ◽  
Innate Immune ◽  
Enterotoxigenic Escherichia Coli ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Genomic Study ◽  
Etec Infection

Pharmacological levels of zinc oxide in the post-weaning piglet diet reduce the incidence and severity of diarrhoea, in particular that caused by enterotoxigenic Escherichia coli (ETEC) K88 (Owusu-Asiedu et al. 2003). A previous in vivo genomic study (Sargeant et al, 2008) identified several genes differentially expressed in the small intestine of ETEC-challenged piglets when fed a zinc oxide-supplemented diet. This included decreased expression of several genes involved in the inflammatory and innate immune response. It has been reported that ZnO reduces adhesion and internalisation of K88 to cultured human enterocytes, counteracting the up-regulation of inflammatory cytokines caused by ETEC infection. However, this effect was not due to growth inhibition of ETEC K88 in ZnO (Roselli et al, 2003). The objective of this study was to determine whether zinc oxide shows the same mode of action in protecting porcine intestinal cells against ETEC K88 as has been demonstrated in human cells, providing an explanation for in vivo findings.

Безопасность соединений из группы терпенов ментанового ряда in vitro и in vivo

2020 ◽  
Vol 83 (4) ◽  
pp. 24-30
Author(s):  
Ирина Владимировна Акулина ◽  
Светлана Ивановна Павлова ◽  
Ирина Семеновна Степаненко ◽  
Назира Сунагатовна Карамова ◽  
Александр Владиславович Сергеев ◽  
...  
Keyword(s):  
Escherichia Coli

Проведено токсикологическое исследование соединений с антибактериальными свойствами из группы терпенов ментанового ряда в условиях in vitro и in vivo: лимонена (B34), его производного (+)-1,2-оксида лимонена (B60) и серосодержащего монотерпенового соединения 2-(1’-гидрокси-4’-изопренил-1’-метилциклогексил-2’-тио)метилэтаноата (B65). В условиях in vitro (культура опухолевых клеток HeLa) изучаемые монотерпены в диапазоне концентраций 2 – 200 мкг/мл обладали цитотоксичностью. Ингибирующая концентрация (ИК50) для B34 составила 231 (167 – 295) мкг/мл, для B60 – 181 (105 – 257) мкг/мл, ИК50 B65 – 229 (150 – 308) мкг/мл. Исследование генотоксичности показало, что B34 и B65 в диапазоне концентраций 50 – 1000 мкг/мл не индуцируют SOS мутагенез в клетках Escherichia coli PQ37, тогда как B60 в концентрациях 500 и 1000 мкг/мл проявляет генотоксичность. In vivo в остром эксперименте на беспородных мышах установлена низкая токсичность B34 и его производных при различных путях введения. Наименьший показатель острой токсичности имеет B65, в связи с чем дополнительно на крысах проведено изучение его хронической токсичности. Ежедневное внутрижелудочное введение B65 в разовых дозах, составляющих 1/10 и 1/20 ЛД50 (1000 мг/кг и 500 мг/кг), в течение 1 мес не вызывало гибели животных, значимых нарушений общего состояния, изменения динамики массы тела, морфопатологических изменений. Внутрижелудочное введение B65 крысам в высокой токсической дозе 2000 мг/кг (1/5 ЛД50) в течение месяца вызывает патоморфологические изменения структуры печени.

Garlic Extract (Allium sativum L.) Effectively Inhibits Staphylococcus aureus and Escherichia coli by Invitro Test

2020 ◽  
Vol 2 (2) ◽  
pp. 61-68
Author(s):  
Agnina Listya Anggraini ◽  
Ratih Dewi Dwiyanti ◽  
Anny Thuraidah
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Allium Sativum ◽  
Antibacterial Properties ◽  
Herbal Medicines ◽  
Garlic Extract ◽  
Dilution Method ◽  
Initial Stage

Infection is a disease caused by the presence of pathogenic microbes, including Staphylococcus aureus and Escherichia coli. Garlic (Allium sativum L.) has chemical contents such as allicin, alkaloids, flavonoids, saponins, tannins, and steroids, which can function as an antibacterial against Staphylococcus aureus and Escherichia coli. This study aims to determine the antibacterial properties of garlic extract powder against Staphylococcus aureus and Escherichia coli. This research is the initial stage of the development of herbal medicines to treat Staphylococcus aureus and Escherichia coli infections. The antibacterial activity test was carried out by the liquid dilution method. The concentrations used were 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL and 70 mg/mL. The results showed that the Minimum Inhibitory Concentration (MIC) against Staphylococcus aureus and Escherichia coli was 40 mg/mL and 50 mg / mL. Minimum Bactericidal Concentration (MBC) results for Staphylococcus aureus and Escherichia coli are 50 mg/mL and 70 mg/mL. Based on the Simple Linear Regression test, the R2 value of Staphylococcus aureus and Escherichia coli is 0.545 and 0.785, so it can be concluded that there is an effect of garlic extract powder on the growth of Staphylococcus aureus and Escherichia coli by 54.5% and 78.5%. Garlic (Allium sativum L.) extract powder has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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