scholarly journals Long-term effects of the proline-rich antimicrobial peptide Oncocin112 on the Escherichia coli translation machinery

2020 ◽  
Vol 295 (38) ◽  
pp. 13314-13325
Author(s):  
Yanyu Zhu ◽  
James C. Weisshaar ◽  
Mainak Mustafi
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Peptides ◽  
Binding Site ◽  
Elongation Factor ◽  
Microscopy Study ◽  
Single Step ◽  
Long Term Effects ◽  
Bacterial Membranes

Proline-rich antimicrobial peptides (PrAMPs) are cationic antimicrobial peptides unusual for their ability to penetrate bacterial membranes and kill cells without causing membrane permeabilization. Structural studies show that many such PrAMPs bind deep in the peptide exit channel of the ribosome, near the peptidyl transfer center. Biochemical studies of the particular synthetic PrAMP oncocin112 (Onc112) suggest that on reaching the cytoplasm, the peptide occupies its binding site prior to the transition from initiation to the elongation phase of translation, thus blocking further initiation events. We present a superresolution fluorescence microscopy study of the long-term effects of Onc112 on ribosome, elongation factor-Tu (EF-Tu), and DNA spatial distributions and diffusive properties in intact Escherichia coli cells. The new data corroborate earlier mechanistic inferences from studies in vitro. Comparisons with the diffusive behavior induced by the ribosome-binding antibiotics chloramphenicol and kasugamycin show how the specific location of each agent's ribosomal binding site affects the long-term distribution of ribosomal species between 30S and 50S subunits versus 70S polysomes. Analysis of the single-step displacements from ribosome and EF-Tu diffusive trajectories before and after Onc112 treatment suggests that the act of codon testing of noncognate ternary complexes (TCs) at the ribosomal A-site enhances the dissociation rate of such TCs from their L7/L12 tethers. Testing and rejection of noncognate TCs on a sub-ms timescale is essential to enable incorporation of the rare cognate amino acids into the growing peptide chain at a rate of ∼20 aa/s.

scholarly journals Differential interleukin-1β induction by uropathogenic Escherichia coli correlates with its phylotype and serum C-reactive protein levels in Korean infants

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jong-Hyeok Jung ◽  
Hyun Jung Hong ◽  
Aziz Gharderpour ◽  
Jae Young Cho ◽  
Bum-Seo Baek ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Renal Scarring ◽  
Long Term Effects ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Serum Crp

Abstract Urinary tract infection (UTI) is one of the most common bacterial infections in infants less than age 1 year. UTIs frequently recur and result in long-term effects include sepsis and renal scarring. Uropathogenic Escherichia coli (UPEC), the most prevalent organism found in UTIs, can cause host inflammation via various virulence factors including hemolysin and cytotoxic necrotizing factors by inducing inflammatory cytokines such as interleukin (IL)-1β. However, the ability of each UPEC organism to induce IL-1β production may differ by strain. Furthermore, the correlation between differential IL-1β induction and its relevance in pathology has not been well studied. In this study, we isolated UPEC from children under age 24 months and infected bone-marrow derived macrophages with the isolates to investigate secretion of IL-1β. We found that children with higher concentrations of C-reactive protein (CRP) were more likely to harbor phylotype B2 UPEC strains that induced more IL-1β production than phylotype D. We also observed a significant correlation between serum CRP level and in vitro IL-1β induction by phylotype B2 UPEC bacteria. Our results highlight the diversity of UPEC in terms of IL-1β induction capacity in macrophages and suggest a potential pathogenic role in UTIs by inducing inflammation in infants.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

Long-Term Treatment with Pivmecillinam in Patients with Recurrent Bacteriuria

1982 ◽  
Vol 10 (3) ◽  
pp. 179-182
Author(s):  
B Bresky ◽  
K Lincoln
Keyword(s):  
Escherichia Coli ◽  
Adverse Effect ◽  
Renal Function ◽  
Term Treatment ◽  
The Body ◽  
End Of Treatment ◽  
Long Term Treatment ◽  
Tract Infections

Thirty out-patients with chronic recurrent urinary tract infections, who had failed to respond to 10 days treatment with either pivmecillinam and/or amoxycillin, received a 3-month course of pivmecillinam at a dose of 200 mg, three times daily. Twenty-seven patients had bacteriuria due to Enterobacteriaceae, mainly Escherichia coli, sensitive to mecillinam in vitro. Pivmecillinam eradicated all the initial urinary pathogens. Reinfections occurred during treatment in three patients, who remained asymptomatic. Four subjects complained of gastro-intestinal side-effects, and therapy was withdrawn in three instances. Another three patients described unusual adverse events towards the end of the course of treatment, described as an odd sensation in the body and a desire for salt. The sensation disappeared a few days after the end of treatment. Treatment with pivmecillinam had no adverse effect on haematopoietic, hepatic or renal function.

scholarly journals Phenotypical antimicrobial resistance data of clinical and non-clinical Escherichia coli from poultry in Germany between 2014 and 2017

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243772
Author(s):  
Octavio Mesa-Varona ◽  
Heike Kaspar ◽  
Mirjam Grobbel ◽  
Bernd-Alois Tenhagen
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Clinical Isolates ◽  
Long Term Effects ◽  
Time Intervals ◽  
Explanatory Factors ◽  
Global Threat ◽  
Changes Over Time ◽  
Resistance Data

Antimicrobial resistance (AMR) is a global threat in humans and animals, and antimicrobial usage (AMU) has been identified as a main trigger of AMR. The purpose of this work was to compare data on AMR in clinical and non-clinical isolates of Escherichia coli in German broilers and turkeys between 2014 and 2017. Furthermore, we investigated AMR changes over time and the association of changes in AMU with changes in AMR. Data on clinical and non-clinical isolates together with data on therapy frequency of broilers and turkeys were collected from German monitoring systems. Logistic regression analyses were performed to assess the association between the explanatory factors (AMU, year and isolate type) and the dependent variable (AMR). In broilers, the analysis showed lower resistance proportions of clinical isolates of E. coli to ampicillin and colistin (ampicillin: Odds ratio (OR) and 95% confidence interval (CI) = 0.44 (0.3–0.64), p<0.001; colistin: OR and 95% CI = 0.75 (0.73–0.76), p<0.001) but higher proportions for cefotaxime (OR and 95% CI = 4.58 (1.56–15.1), p = 0.007). Resistance to ampicillin, gentamicin and tetracycline was less frequent in clinical isolates in turkeys (ampicillin: OR and 95% CI = 0.4 (0.29–0.53), p<0.001; gentamicin: OR and 95% CI = 0.5 (0.26–0.94), p = 0.035; tetracycline: OR and 95% CI = 0.4 (0.29–0.55), p<0.001). The analysis found decreasing associations of AMU with resistance to tetracycline in turkeys and to colistin in broilers. Year was associated with a decrease in resistance to colistin in broilers and to tetracycline in turkeys. Differences in resistance found in this study between clinical and non-clinical isolates might play an important role in resistance prevalence. This study indicated that further data analyses over longer time intervals are required to clarify the differences found between clinical and non-clinical isolates and to assess the long-term effects of changes in AMU on the prevalence of AMR.

Reproductive fluids, added to the culture media, contribute to minimizing phenotypical differences between in vitro-derived and artificial insemination-derived piglets

2022 ◽  
pp. 1-13
Author(s):  
Evelyne París-Oller ◽  
Cristina Soriano-Úbeda ◽  
Ramsés Belda-Pérez ◽  
Lucía Sarriás-Gil ◽  
Jordana S. Lopes ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Culture Media ◽  
Growth Parameters ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Long Term Effects ◽  
Hematological Indices ◽  
Reproductive Techniques

Abstract The addition of reproductive fluids (RF) to the culture media has shown benefits in different embryonic traits but its long-term effects on the offspring phenotype are still unknown. We aimed to describe such effects in pigs. Blood samples and growth parameters were collected from piglets derived from in vitro-produced embryos (IVP) with or without RF added in the culture media versus those artificially inseminated (AI), from day 0 to month 6 of life. An oral glucose tolerance test was performed on day 45 of life. We show here the first comparative data of the growth of animals produced through different assisted reproductive techniques, demonstrating differences between groups. Overall, there was a tendency to have a larger size at birth and faster growth in animals derived from in vitro fertilization and embryo culture versus AI, although this trend was diminished by the addition of RFs to the culture media. Similarly, small differences in hematological indices and glucose tolerance between animals derived from AI and those derived from IVP, with a sex-dependent effect, tended to fade in the presence of RF. The addition of RF to the culture media could contribute to minimizing the phenotypical differences between the in vitro-derived and AI offspring, particularly in males.

scholarly journals Metformin decreases hyaluronan synthesis by vascular smooth muscle cells

2019 ◽  
Vol 68 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Annele Sainio ◽  
Piia Takabe ◽  
Sanna Oikari ◽  
Henriikka Salomäki-Myftari ◽  
Markku Koulu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Response To Treatment ◽  
Long Term Effects

Metformin is the first-line drug in the treatment of type 2 diabetes worldwide based on its effectiveness and cardiovascular safety. Currently metformin is increasingly used during pregnancy in women with gestational diabetes mellitus, even if the long-term effects of metformin on offspring are not exactly known. We have previously shown that high glucose concentration increases hyaluronan (HA) production of cultured human vascular smooth muscle cells (VSMC) via stimulating the expression of hyaluronan synthase 2 (HAS2). This offers a potential mechanism whereby hyperglycemia leads to vascular macroangiopathy. In this study, we examined whether gestational metformin use affects HA content in the aortic wall of mouse offspring in vivo. We also examined the effect of metformin on HA synthesis by cultured human VSMCs in vitro. We found that gestational metformin use significantly decreased HA content in the intima-media of mouse offspring aortas. In accordance with this, the synthesis of HA by VSMCs was also significantly decreased in response to treatment with metformin. This decrease in HA synthesis was shown to be due to the reduction of both the expression of HAS2 and the amount of HAS substrates, particularly UDP-N-acetylglucosamine. As shown here, gestational metformin use is capable to program reduced HA content in the vascular wall of the offspring strongly supporting the idea, that metformin possesses long-term vasculoprotective effects.

scholarly journals Prolonged Amphetamine Treatments Cause Long-Term Decrease of Dopamine Uptake in Cultured Cells

2019 ◽  
Vol 45 (6) ◽  
pp. 1399-1409
Author(s):  
Nafisa Ferdous ◽  
Sirisha Kudumala ◽  
Serena Sossi ◽  
Lucia Carvelli
Keyword(s):  
Cultured Cells ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Long Term Effects ◽  
Human Neuroblastoma ◽  
Daughter Cells ◽  
Cell Divisions

AbstractAmphetamine (AMPH) is a systemic stimulant used to treat a variety of diseases including Attention Deficit Hyperactive Disorder, narcolepsy and obesity. Previous data showed that by binding to catecholamine transporters, AMPH prevents the reuptake of the neurotransmitters dopamine (DA) and norepinephrine (NE). Because AMPH, either used therapeutically at final concentrations of 1–10 µM or abused as recreational drug (50–200 µM), is taken over long periods of time, we investigated the prolonged effects of this drug on the uptake of DA. We found that, in LLC-PK1 cells stably expressing the human DA transporter (hDAT), pretreatments with 1 or 50 µM AMPH caused significant reduction in DA uptake right after the 15-h pretreatment. Remarkably, after 50 but not 1 µM AMPH pretreatment, we observed a significant reduction in DA uptake also after one, two or three cell divisions. To test whether these long-term effects induced by AMPH where conserved in a model comparable to primordial neuronal cells and native neurons, we used the human neuroblastoma cell line SH-SY5Y cells, which were reported to endogenously express both hDAT and the NE transporter. Pretreatments with 50 µM AMPH caused a significant reduction of DA uptake both right after 15 h and 3 cell divisions followed by neuro-differentiation with retinoic acid (RA) for 5 days. Under these same conditions, AMPH did not change the intracellular concentrations of ATP, ROS and cell viability suggesting, therefore, that the reduction in DA uptake was not cause by AMPH-induced toxicity. Interestingly, while 1 µM AMPH did not cause long-term effects in the LLC-PK1 cells, in the SH-SY5Y cells, it decreased the DA uptake after one, two, but not three, cell divisions and 5-day RA differentiation. These data show that besides the well-known acute effects, AMPH can also produce long-term effects in vitro that are maintained during cell division and transmitted to the daughter cells.

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