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Abstract. Urinary tract infections (UTIs) are among the most common causes of infections in women. Via the fecal-perineal-urethral route, uropathogenic Escherichia coli (UPEC) can cause ascending urinary tract infections, including cystitis and pyelonephritis. These infections re-occur within six months or they account for, at least, three episodes within a year of recurrent UTIs (rUTIs). Long term and continuous antibiotic treatment or prophylaxis should be considered as the last options in rUTIs. Conversely, updated European Association of Urology guidelines recommend non-antimicrobial approaches to prevent rUTIs. Accordingly, several studies reported the efficacy of number of natural molecules in inhibiting UPEC adhesion to bladder cells, restraining bacterial growth, as well as stimulating the host innate immune defenses, and protecting the bladder and the kidney mucosa. Therefore, we propose an “anti-UPEC” diet enriched of foods containing natural compounds that were proven effective against UPEC, such as D-mannose, cranberry extracts and medicinal plants. Being a valuable and safe clinical approach to reduce UTI recurrence and limiting the detrimental effects of long and continuous antibiotic prophylaxis, dietary interventions should be evaluated in future clinical trials.

Escherichia coli infections can result in lung injury, which may be closely linked to the induction of interferon secretion. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is one of most important pathways that regulate interferon production. Thus, the present study aimed to dissect whether E. coli infections can regulate interferon production and the underlying mechanisms. For this aim, two lung cell lines, a human bronchial epithelial cell line transformed with Ad12-SV40 2B (BEAS-2b) and a human fetal lung fibroblast (HFL1) cell line, were used. The effects of E. coli infections on interferon production were studied using qRT-PCR, Western blot, and siRNA knockdown assays. E. coli infections remarkably promoted the expression levels of IFN-α, IFN-β, and ISGs. Major components of the JAK/STAT pathway, including JAK1, STAT1, and STAT2, were demonstrated to be regulated by E. coli infections. Importantly, knockdown of JAK1, STAT1, and STAT2 abolished the induction of IFN-α, IFN-β, and ISGs by E. coli. Therefore, experiments in the present study demonstrated that E. coli infections remarkably promoted interferon production in lung cells, which was closely regulated by the JAK/STAT signaling pathway. The findings in the present study are useful for further understanding the pathogenesis of E. coli infections in the lung and finding novel therapies to treat E. coli-induced lung injury.

Background Escherichia coli is the most common Gram-negative bacterium causing meningitis, and E. coli meningitis is associated with high mortality and morbidity throughout the world. Our previous study showed that E. coli can colonize the brain and cause neuroinflammation. Increasing evidence supports the involvement of miRNAs as key regulators of neuroinflammation. However, it is not clear whether these molecules participate in the regulation of meningitic E. coli-mediated neuroinflammation. Methods The levels of miR-155 and miR-146a, as well as their precursors, in E. coli-infected astrocytes were measured using quantitative real-time PCR (qPCR). Overexpression and knockdown studies of miR-155 and miR-146a were performed to observe the effects on bacterial loads, cytokines, chemokines, and NF-κB signaling pathways. Bioinformatics methods were utilized to predict the target genes, and these target genes were validated using qPCR, Western blotting, and luciferase reporter system. In vivo knockdown of miR-155 and miR-146a was carried out to observe the effects on bacterial loads, inflammatory genes, astrocyte activation, microglia activation, and survival in a mouse model. Results The levels of miR-155, miR-146a, and their precursors were significantly increased in astrocytes during E. coli infection. miR-155 and miR-146a were induced by the NF-κB-p65 signaling pathway upon infection. Overexpressing and inhibiting miR-155 and miR-146a in astrocytes did not affect the bacterial loads. Further, the in vitro overexpression of miR-155 and miR-146a suppressed the E. coli-induced inflammatory response, whereas the inhibition of miR-155 and miR-146a enhanced it. Mechanistically, miR-155 inhibited TAB2, and miR-146a targeted IRAK1 and TRAF6; therefore, they functioned collaboratively to modulate TLR-mediated NF-κB signaling. In addition, both miR-155 and miR-146a could regulate the EGFR–NF-κB signaling pathway. Finally, the in vivo suppression of E. coli-induced miR-155 and miR-146a further promoted the production of inflammatory cytokines, aggravated astrocyte and microglia activation, and decreased mouse survival time, without affecting the bacterial loads in the blood and brain. Conclusions E. coli infection induced miR-155 and miR-146a, which collectively regulated bacteria-triggered neuroinflammatory responses through negative feedback regulation involving the TLR-mediated NF-κB and EGFR–NF-κB signaling pathways, thus protecting the central nervous system from further neuroinflammatory damage.

Objective: In this case report, we have investigated the infectious bronchitis (IB) virus (IBV) out¬break with the co-infection of Escherichia coli in 2833-day-old broiler chickens in Malaysia. Materials and Methods: A farmer complained that Cobb 500 chickens, raised in the open house, were having bloody diarrhea, open mouth breathing, non-uniform growth, and ruffled feathers. The mortality was about 100 birds (from about 7000 birds) per day. The sick birds were isolated and subjected to physical examination, postmortem, and histopathological analyses. Gross lesions were observed and recorded. The lung samples have proceeded with histopathological evalua¬tions. The lungs, kidneys, trachea, air sac, and heart samples were collected to isolate bacteria and fungi through a series of conventional cultural methods, followed by molecular confirmation of the IBV. Results: Postmortem examination revealed air sacculitis, hemorrhagic tracheitis, pulmonary con¬gestion, fibrin deposition in the liver and air sac, hemorrhagic enteritis, and renomegaly. The bacterial culture and biochemical tests revealed E. coli in the lungs, trachea, liver, intestine, and kidney samples. However, no fungus could be isolated from those samples. Histological evalua¬tion of lung samples demonstrated infiltration of inflammatory cells in the pulmonary tissues. Apart from this, reverse transcription-polymerase chain reaction confirmed the presence of avian coronavirus responsible for infectious bronchitis (IB). Conclusion: The chickens were diagnosed with IB concurrent with E.coli. The chickens exhibited typical nephropathogenic strain of IBV infection, causing high mortality. [J Adv Vet Anim Res 2021; 8(1.000): 101-104]

We characterized the antimicrobial resistance of 70 Escherichia coli isolates obtained from patients with a urinary tract infection (UTI) from 8 public hospitals in Peru. Resistance profiles were identified using the automated MicroScan® system. A standard polymerase chain reaction was used for the detection of the bla TEM, bla CTX-M, bla SHV and bla PER genes. The 65.7% (46/70) of the isolates presented a multidrug-resistant phenotype and 55.7% (39/70) were extended-spectrum beta-lactamases producers. High levels of resistance were detected for ampicillin (77,1%), ciprofloxacin (74,3%), trimethoprim/sulfamethoxazole (62,9%), cefepime (57,1%), and cefuroxime (57,1%). The bla TEM gene was the most frequent (31,4%), followed by bla CTX-M (18,6%) and bla SHV (2,9%) genes. These results show high resistance levels to antimicrobials of clinical use in E. coli isolates from hospital UTI patients in Peru.Se caracterizó la resistencia antimicrobiana de 70 aislados de Escherichia coli obtenidos de pacientes con infección del tracto urinario (ITU) provenientes de ocho hospitales públicos en el Perú. Los perfiles de resistencia fueron identificados mediante el uso del sistema automatizado MicroScan®. Se utilizó una reacción en cadena de la polimerasa convencional para la detección de los genes bla TEM, bla CTX-M, bla SHV y bla PER. El 65,7% (46/70) de los aislados presentó un fenotipo multidrogorresistente y el 55,7% (39/70) fue identificado como productores de betalactamasas de espectro extendido. Se detectaron altos niveles de resistencia para ampicilina (77,1%), ciprofloxacina (74,3%), trimetoprim/sulfametoxazol (62,9%), cefepime (57,1%) y cefuroxima (57,1%). El gen bla TEM fue el más frecuente con un 31,4%, seguido por bla CTX-M (18,6%) y bla SHV (2,9%). Los resultados evidencian altos niveles de resistencia a antimicrobianos de importancia clínica en aislados de E. coli de pacientes con ITU en el Perú.

Antivirulence therapy by cell membrane coated nanoparticles has shown promise against bacterial infections. However, current approaches remain unsatisfactory when facing Escherichia coli (E. coli) infections, since the E. coli secretes multiple bacterial toxins including endotoxins and exotoxins that are challenging to eliminate simultaneously. What is worse, the absorptive scavengers normally rely on random contact of the diffuse toxins, which is not efficient. For the current cell membrane coated platform, the single type of cell membrane cannot fully meet the detoxing requirement facing multiple toxins. To address these problems, a polymyxin B (PMB)-modified, red blood cell (RBC)-mimetic hybrid liposome (P-RL) was developed. The P-RL was fabricated succinctly through fusion of PMB-modified lipids and the RBC membranes. By the strong interaction between PMB and the E. coli membrane, P-RL could attach and anchor to the E. coli; attributed to the fused RBC membrane and modified PMB, the P-RL could then efficiently neutralize both endotoxins and exotoxins from the toxin fountainhead. In vitro and in vivo results demonstrated the P-RL had a significant anchoring effect to E. coli. Moreover, compared with the existing RBC vesicles or PMB-modified liposomes, P-RL exhibited a superior therapeutic effect against RBC hemolysis, macrophage activation, and a mixed-toxin infection in mice. Potently, P-RL could inhibit E. coli O157:H7-induced skin damage, intestinal infection, and mouse death. Overall, the P-RL could potentially improve the detoxing efficiency and markedly expand the detoxification spectrum of current antivirulence systems, which provides different insights into drug-resistant E. coli treatment.

Aim: To investigate the mRNAs and noncoding RNAs (ncRNAs) expression in astrocytes upon meningitic- Escherichia coli infection. Materials & methods: The transcription of mRNAs and ncRNAs were fully investigated and profiled by whole transcriptome sequencing and bioinformatic approaches. Whole transcriptome differences between the infected astrocytes and brain microvascular endothelial cells were further compared and characterized. Results: A total of 2045 mRNAs, 74 long noncoding RNAs, 27 miRNAs and 418 circular RNAs were differentially transcribed in astrocytes upon infection. Competing endogenous RNAs regulatory networks were constructed and preliminary validated. Transcriptomic differences between astrocyte and brain microvascular endothelial cells revealed the cell-specific responses against the infection. Conclusion: Our study comprehensively characterized the ncRNAs and mRNAs profiles in astrocytes upon meningitic- E. coli infection, which will facilitate future functional studies.

Formyl peptide receptors (FPRs, mouse Fprs) belong to the G protein–coupled receptor superfamily and mediate phagocyte migration in response to bacteria- and host-derived chemoattractants; however, knowledge about their in vivo roles in bacterial pathogenesis is limited. In this study, we investigated the role of Fpr1 and Fpr2 in host defense against Escherichia coli infection. In vitro, we found that supernatants from E. coli cultures induced chemotaxis of wild-type (WT) mouse bone marrow–derived neutrophils and that the activity was significantly reduced in cells genetically deficient in either Fpr1 or Fpr2 and was almost absent in cells lacking both receptors. Consistent with this, E. coli supernatants induced chemotaxis and MAPK phosphorylation in HEK293 cells expressing either recombinant Fpr1 or Fpr2 but not untransfected parental cells. WT bone marrow –derived neutrophils could actively phagocytose and kill E. coli, whereas both activities were diminished in cells lacking Fpr1 or Fpr2; again, an additive effect was observed in cells lacking both receptors. In vivo, Fpr1 and Fpr2 deficiency resulted in reduced recruitment of neutrophils in the liver and peritoneal cavity of mice infected with inactivated E. coli. Moreover, Fpr1−/− and Fpr2−/− mice had significantly increased mortality compared with WT mice after i.p. challenge with a virulent E. coli clinical isolate. These results indicate a critical role of Fprs in host defense against E. coli infection.

Chorioamnionitis is an acute inflammation of the membranes and chorion of the placenta typically due to ascending polymicrobial infection in the setting of membrane rupture. It is a common complication of pregnancy associated with significant maternal, perinatal, and long‐term adverse outcomes. We present a case of placental infection leading to preterm delivery, severe neonatal sepsis, maternal wound infection, postnatal readmission, and prolonged hospital stay. This virulent infection was caused by multidrug–resistant extended‐spectrum beta‐lactamase (ESBL)‐producing Escherichia Coli (E. Coli), which represent a major worldwide threat according to the Centre for Disease Control and Prevention (CDC). It was managed with appropriate antibiotic therapy, patient‐centered approach, and multidisciplinary team involvement that led to favourable maternal and neonatal outcome., Chorioamnionitis is a fetomaternal condition that can be caused by ESBL‐producing E. coli which pose challenging infection control issues and are a serious global threat. Screening strategies to monitor them could be useful in women from endemic areas to prevent perinatal transmission and introduction of multiresistant strains to the maternity wards.

Infections of the thyroid gland are rare. Its innate resistance to infections can be attributed to its unique anatomical features and rich blood supply. High clinical suspicion is required as a delay in diagnosis can lead to significant morbidity and mortality. Major pathogens include the Gram-positive Staphylococcus aureus and Streptococcus species; however, Gram-negative organisms have been found especially in immunocompromised hosts. We present a rare case of acute suppurative thyroiditis (AST) secondary to Escherichia coli (E. coli) infection in a woman known to be infected with human immunodeficiency virus (HIV). LEARNING POINTS Thyroid abscesses are rare and can be confused with more common pathologies involving the neck such as a goitre, adenoma, intracystic haemorrhage, pharyngeal abscess and subacute thyroiditis. A high index of suspicion for a thyroid abscess is required for patients who present with an anterior neck swelling to avoid a late diagnosis, which is associated with significant morbidity and mortality. Acute suppurative thyroiditis is more commonly caused by Gram-positive organisms. Gram-negative organisms such as E. coli remain a rare cause. However, if a thyroid abscess is suspected clinically, broad-spectrum antibiotics can be lifesaving before definite culture and sensitivity results are available.

The exploration of multiplexed bacterial virulence factors is a major problem in the early stages of Escherichia coli infection therapy. Traditional methods for detecting Escherichia coli (E. coli), such as serological experiments, immunoassays, polymerase chain reaction, and isothermal microcalorimetry have some drawbacks. As a result, detecting E. coli in a timely, cost-effective, and sensitive manner is critical for various areas of human safety and health. Intelligent devices based on nanotechnology are paving the way for fast and early detection of E. coli at the point of care. Due to their specific optical, magnetic, and electrical capabilities, nanostructures can play an important role in bacterial sensors. Another one of the applications involved use of nanomaterials in fighting microbial infections, including E. coli mediated infections. Various types of nanomaterials, either used directly as an antibacterial agent such as metallic nanoparticles (NPs) (silver, gold, zinc, etc.), or as a nanocarrier to deliver and target the antibiotic to the E. coli and its infected area. Among different types, polymeric NPs, lipidic nanocarriers, metallic nanocarriers, nanomicelles, nanoemulsion/ nanosuspension, dendrimers, graphene, etc. proved to be effective vehicles to deliver the drug in a controlled fashion at the targeted site with lower off-site drug leakage and side effects.

Polymyxin B has been re‐applied to the clinic as the final choice for the treatment of multidrug‐resistant gram‐negative pathogenic infections, but the use of polymyxin B has been re‐assessed because of the emergence and spread of the plasmid‐mediated mcr‐1 gene. The purpose of this study was to search for an MCR inhibitor synergistically acting with polymyxin to treat the infection caused by this pathogen. In this study, we used the broth microdilution checkerboard method to evaluate the synergistic effect of isoalantolactone (IAL) and polymyxin B on mcr‐1‐positive Enterobacteriaceae. Growth curve analysis, time‐killing assays and a combined disc test were used to further verify the efficacy of the combined drug. Colonization of the thigh muscle in mice, survival experiments and lung tissue section observations was used to determine the effect of synergy in vivo after Klebsiella pneumoniae and Escherichia coli infection. We screened a natural compound, IAL, which can enhance the sensitivity of polymyxin B to mcr‐1‐positive Enterobacteriaceae. The results showed that the combined use of polymyxin B and IAL has a synergistic effect on mcr‐1‐positive Enterobacteriaceae, such as K pneumoniae and E coli, not only in vitro but also in vivo. Our results indicate that IAL is a natural compound with broad application prospects that can prolong the service life of polymyxin B and make outstanding contributions to the treatment of gram‐negative Enterobacteriaceae infections resistant to polymyxin B.

Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in children (< 3 years), is mainly related to Shiga toxins (Stx)-producing Escherichia coli (STEC) infections. STEC are confined to the gut resulting in hemorrhagic colitis, whereas Stx are delivered in blood to target kidney and brain, with unclear mechanisms, triggering HUS in 5 to 15% of infected children. Stx were found on circulating cells, free in sera (soluble Stx) or in blood cell-derived microvesicles (particulate Stx), whereby the relationship between these forms of circulating toxins is unclear. Here, we have examined 2,846 children with bloody diarrhea and found evidence of STEC infection in 5%. Twenty patients were enrolled to study the natural course of STEC infections before the onset of HUS. In patients, Stx were found to be associated to circulating cells and/or free and functionally active in sera. In most children, Stx were bound to neutrophils when high amounts of toxins were found in feces. Time-course analysis showed that Stx increased transiently in patients' sera while the decrease of toxin amount on leukocytes was observed. Notably, patients who recovered (85%) displayed different settings than those who developed HUS (15%). The distinctive feature of the latter group was the presence in blood of particulate Stx2 (Stx2 sedimented at g-forces corresponding to 1 μm microvesicles) the day before diagnosis of HUS, during the release phase of toxins from circulating cells. This observation strongly suggests the involvement of blood cell-derived particulate Stx2 in the transition from hemorrhagic colitis to HUS.

Urinary tract infections caused by the bacterium Escherichia coli are among the most frequently encountered infections and are a common reason for antimicrobial prescriptions. Resistance to fluoroquinolone antimicrobial agents, particularly ciprofloxacin, has increased in recent decades. It is intuitive that variation in fluoroquinolone resistance is driven by changes in antimicrobial use, but careful study of this association requires the use of time-series methods. Between April 2010 and December 2014, we studied seasonal variation in resistance to ciprofloxacin, trimethoprim-sulfamethoxazole, and ampicillin in community-acquired urinary E. coli isolates in Montreal, Quebec, Canada. Using dynamic linear models, we investigated whether seasonal variation in resistance could be explained by seasonal variation in community antimicrobial use. We found a positive association between total fluoroquinolone use lagged by 1 and 2 months and the proportion of isolates resistant to ciprofloxacin. Our results suggest that resistance to ciprofloxacin is responsive to short-term variation in antimicrobial use. Thus, antimicrobial stewardship campaigns to reduce fluoroquinolone use, particularly in the winter when use is highest, are likely to be a valuable tool in the struggle against antimicrobial resistance.

The bovine endometrium is constantly challenged with pathogenic bacteria, especially with Escherichia coli. In previous studies, we showed that prostaglandin E2 (PGE2) synthesis was increased in E. coli-infected bovine endometrial tissue, which promoted the development of inflammatory damage. However, the molecular mechanism underlying this accumulation of PGE2 remained undefined. Lipoprotein (LP) is one of critical outer membrane protein in E. coli, which regulates inflammatory response. In this study, we determined the role of LP in PGE2 accumulation in bovine endometrial tissue by infecting the tissue with wild endometrial pathogenic E. coli and E. coli LP deletion mutant (JE5505) strains. We demonstrate that JE5505 was less effective than pathogenic E. coli in inducing the production of PGE2,IL-6, TNF-α, HMGB-1, and HABP1 and that the induction of cytokines was dependent on the activation of MAPKs, as revealed by rapid phosphorylation of ERK1/2/NF-κB in the endometrial tissues, furthermore, LP also induced PGE2 synthessis and cytokine secretion. Additionally, ERK and NF-κB inhibitors significantly inhibited PGE2 production and cytokine secretion and reduced or attenuated tissue damage in JE5505-infected and LP induced endometrial tissues. What is more important, we reported PGE2 introduction increased the expression of pro-inflammatory factors and DAMPs in E. coli-infected bovine endometrial tissue. Taken together, these results indicate that LP is involved in the accumulation of PGE2 through the activation of the ERK/NF-κB pathway that induces the production of pro-inflammatory factors and damage-associated molecular patterns (DAMPs) in E. coli-infected bovine endometrial tissue. These results should help in better understanding and management of postpartum inflammatory diseases in dairy cows.

Bacterial infection causes nutrient malabsorption in small intestine. KR-32, a kind of synthetic antimicrobial peptide, has the bacteriostatic effect. In the present study, 2 experiments were designed to analyze the effects of KR-32 on fat absorption of piglets with or without Escherichia coli infection. In Exp. 1, 12 weaning piglets (21 d old) were allocated to 2 groups: piglets with an intraperitoneal (i.p.) injection of antimicrobial peptide KR-32 (APK) and piglets with an i.p. injection of an equivalent volume (1 mL) of phosphate-buffered saline (PBS) (CON-1). Results showed that after 7 d of growth, KR-32 did not significantly change growth performance and apparent total tract digestibility (ATTD) of feed nutrients of normal pigs. To confirm whether KR-32 affects those of enterotoxigenic Escherichia coli (ETEC) K88-challenged pigs, we performed Exp. 2, in which 18 piglets (28 d old) were divided into the following 3 groups: 1) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of 0.6 mg/kg KR-32 (K88 + APK); 2) piglets orally challenged with 1 × 1010 cfu ETEC K88 on day 1 followed by an i.p. injection of an equivalent volume (1 mL) of PBS (K88); and 3) piglets with an oral administration of fresh Luria-Bertani broth (50 mL) followed by an i.p. injection of an equivalent volume of PBS (CON-2). Results showed that ETEC K88 challenge led to poor ADFI, ADG, and G:F in piglets; decreased ATTD of feed nutrients, especially CP and ether extract (EE); and intestinal morphology disorder. After i.p. injection of KR-32, ADG and ATTD of CP and EE were greatly increased, G:F was significantly reduced (P < 0.05), and, especially, ATTD of EE returned to a normal level compared with group CON-2. Fatty acid absorption also highly increased after KR-32 injection. Then we focused on fat digestion and fatty acid uptake. The pH in the intestine and pancreas lipase showed no difference among the 3 treatment groups, whereas fatty acid transporter protein 4 (FATP4) expression was remarkably improved (P < 0.05) and the epithelial barrier was recovered after i.p. injection of KR-32. In conclusion, KR-32, given to ETEC K88-challenged piglets, improved growth performance, ATTD of EE, fatty acid absorption, and intestinal morphology, which indicated that KR-32 was likely to improve the expression of FATP4 and by repairing the epithelial barrier, thereby alleviating fatty acid malabsorption.

Background Increased resistance to third-generation cephalosporin (3GC) is a serious concern for community-onset Escherichia coli infection because this resistance easily delays effective treatment. This study surveyed the current antimicrobial resistance pattern among E. coli isolates that cause community-onset bacteremia, with a special focus on the prevalence of and the risk factors for 3GC resistance, and determined factors for poor outcomes among patients with community-onset E. coli bacteremia. Methods This retrospective study was conducted at a tertiary-care teaching hospital in Taiwan. All adult patients with community-onset E. coli bacteremia between January 1, 2015, and December 31, 2015 were enrolled and were divided into two groups depending on whether the E. coli isolate was susceptible to 3GCs. Risk factors for 3GC resistance, 14-day all-cause mortality, and length of hospital stay were analyzed. Results The overall rate of 3GC resistance among E. coli isolates causing community-onset bacteremia was 19.7%, whereas it was 9.6% if only isolates causing community-acquired bacteremia were considered. Independent risk factors for 3GC-resistant community-onset E. coli bacteremia were hospitalization within the past 1 year (odds ratio: 2.4, 95% confidence interval: 1.6–3.7, P

The grey predictive mathematical model based on big data was used for analysis on the effect of Escherichia coli infection on patients with lupus nephritis (LN) in this study. Then, 156 patients diagnosed with LN infections by Wuzhong People’s Hospital’s information system (HIS) from October 30, 2017 to October 30, 2019 were selected as the experimental group, and 89 patients without LN infections were selected as the control group. Besides, the grey theory mathematical model was applied to process the integrated data, and feature analysis was employed to screen out disease-related bio-markers for the diagnosis of LN. The two groups were compared for affected organs, treatment, laboratory indicators, pathogenic bacteria, and recovery status. Multivariate logistic regression was used to analyze the related factors of patients with infections. The results showed that the specificity, sensitivity, and accuracy of the big data diagnosis based on the grey theory mathematical model were 78.9%, 87.6%, and 92.1, respectively; hormones, c-reactive protein, procalcitonin, and the daily antibiotic dose were positively correlated with concurrent infections (P

Escherichia coli constitutes an immense challenge to the poultry industry due to its devastating effect on productivity, mortality, and carcass condemnations. To aid future studies on disease mechanisms and interventions, an aerogenous infection model was established in adult broiler breeders. Hens (n = 120) were randomly allocated into six groups receiving either aerosolised E. coli or vehicle, or intratracheal E. coli or vehicle. Replication of aerosol inoculation was performed on distinct days. Alternating euthanasia time points were predetermined in order to evaluate the progression of the disease. All animals were thoroughly necropsied, and bacteriological samples were collected as well as tissues for histopathology. Birds inoculated with E. coli exhibited clinical signs and developed characteristic gross and histopathological lesions of colibacillosis, including splenic fibrinoid necrosis, folliculitis, polyserositis and impaction of parabronchi with fibrinoheterophilic exudate and necrotic debris, as well as positive in situ localisation of intralesional E. coli by immunohistochemistry. This study presents a successful development of a discriminative colibacillosis model through aerosol inoculation of adult broiler breeders. Gross and histopathological lesions characteristic of colibacillosis were established in two independent experiments.

Mastitis caused by Escherichia coli (E. coli) remains a threat to dairy animals and impacts animal welfare and causes great economic loss. Furthermore, antibiotic resistance and the lagged development of novel antibacterial drugs greatly challenge the livestock industry. Phage therapy has regained attention. In this study, three lytic phages, termed vB_EcoM_SYGD1 (SYGD1), vB_EcoP_SYGE1 (SYGE1), and vB_EcoM_SYGMH1 (SYGMH1), were isolated from sewage of dairy farm. The three phages showed a broad host range and high bacteriolytic efficiency against E. coli from different sources. Genome sequence and transmission electron microscope analysis revealed that SYGD1 and SYGMH1 belong to the Myoviridae, and SYGE1 belong to the Autographiviridae of the order Caudovirales. All three phages remained stable under a wide range of temperatures or pH and were almost unaffected in chloroform. Specially, a mastitis infected cow model, which challenged by a drug resistant E. coli, was used to evaluate the efficacy of phages. The results showed that the cocktails consists of three phages significantly reduced the number of bacteria, somatic cells, and inflammatory factors, alleviated the symptoms of mastitis in cattle, and achieved the same effect as antibiotic treatment. Overall, our study demonstrated that phage cocktail may be a promising alternative therapy against mastitis caused by drug resistant E. coli.

The novel virulent Siphoviridae bacteriophage swi2 was isolated from a pig farm, and its biological characteristics, genome architecture, and infection-related properties were characterized. Phage swi2 has a high titer of 1.01 × 1012 PFU/mL with good tolerance to UV rays and remains stable in the pH range of 6–10 and at temperatures less than 50°C. One-step growth analysis revealed that phage swi2 had a 25 min latent period with a large burst size (1,000 PFU/cell). The biological characteristics indicated that swi2 had good host infectivity and effective lytic activities. The genome of phage swi2 is composed of 47,611 bp with a G + C content of 46.50%. Eighty-nine orfs were predicted, and only 18 of them have known functions. No virulence genes or drug resistance genes were found in the genome. Genome sequence comparison of phage swi2 showed that there were a total of 10 homologous phages in the database with low similarity (less than 92.51% nucleotide identity and 66% query coverage). The predicted host lysis-related genes of phage swi2 consist of one holin, two endolysins, and Rz/Rz1 equivalents. Antibacterial activity assays showed that both endolysins could naturally reduce the host Escherichia coli 51 titers by -1 log unit both in vitro and in vivo, EDTA showed no obvious synergistic action, and holin had no lytic effects on the host cell. These results provide necessary information for the development of antibiotic alternatives for the treatment of multidrug-resistant Escherichia coli infection.

Escherichia coli infection is considered one of the most economically important multi-systemic diseases in poultry farms. Several nanoparticles such as silver, chitosan, and copper oxide are known to be highly toxic to several microbes. However, there are no data concerning their success against in vivo experimental E. coli infection in broilers. Therefore, the present study was designed to investigate the bactericidal effect of low doses of CuO-NPs (5 mg/kg bwt), Ag-NPs (0.5 mg/kg bwt), and Ch-Ag NPs (0.5 mg/kg bwt) against E. coli experimental infection in broilers. One hundred chicks were divided into five groups as follows: (1) control; (2) E. coli (4 × 108 CFU/ml) challenged; (3) E. coli +CuO-NPs; (4) E. coli +Ag-NPs; (5) E. coli +Ch-Ag NPs. The challenged untreated group, not NPs treated groups, recorded the lowest weight gain as well as the highest bacterial count and lesion score in all examined organs. The highest liver content of silver was observed in Ag-NPs treated group compared with the Ch-Ag NPs treated group. Our results concluded that Ch-Ag NPs not only had the best antibacterial effects but also acted as a growth promoter in broilers without leaving any residues in edible organs. We recommend using Ch-Ag NPs in broiler farms instead of antibiotics or probiotics.

IMPORTANCE: Escherichia coli is a leading cause of serious infection among term and preterm newborn infants. Surveillance of antibiotic susceptibility patterns of E coli among infants admitted to neonatal intensive care units should inform empirical antibiotic administration. OBJECTIVE: To assess the epidemiologic characteristics and antibiotic susceptibility patterns of E coli in infants admitted to neonatal intensive care units in the US over time. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Premier Health Database, a comprehensive administrative database of inpatient encounters from academic and community hospitals across the US. Participants included newborn infants admitted to centers contributing microbiology data from January 1, 2009, to December 31, 2017, with E coli isolated from blood, cerebrospinal fluid, or urine cultures. Data were collected and analyzed from December 1, 2018, to November 30, 2019. MAIN OUTCOMES AND MEASURES: Changes in annual antibiotic susceptibility of E coli during the study period. The proportion of infants with nonsusceptible organisms (resistant or intermediate susceptibility) in antibiotic categories by year, birth weight, infection source, and timing of infection and patient and center characteristics associated with neonatal E coli infection and antibiotic susceptibility were assessed. RESULTS: A total of 721 infants (434 male [60.2%]; median age at E coli infection, 14 days [interquartile range, 1-33 days]) from 69 centers had at least 1 episode of E coli infection and available susceptibility results. No significant changes were observed over time in the overall annual proportions of antibiotic nonsusceptibility to ampicillin (mean [SD], 66.8% [1.5%]; range, 63.3% to 68.6%; estimated yearly change, −0.28% [95% CI, −1.75% to 1.18%]), nonsusceptibility to aminoglycosides (mean [SD], 16.8% [4.5%]; range, 10.7% to 23.2%; estimated yearly change, −0.85% [95% CI, −1.93% to 0.23%]), or extended-spectrum β-lactamase phenotype (mean [SD], 5.0% [3.7%]; range, 0% to 11.1%; estimated yearly change, 0.46% [95% CI, −0.18% to 1.11%]). No isolates with nonsusceptibility to carbapenems were identified. Among 218 infants with early-onset infection, 22 (10.1%) had isolates with nonsusceptibility to both ampicillin and gentamicin, the antibiotics most commonly administered to newborns as empirical therapy. CONCLUSIONS AND RELEVANCE: In this cohort study, nonsusceptibility to commonly administered antibiotics was found in substantial proportions of neonatal E coli isolates, with no significant change from 2009 to 2017. These findings may inform empirical antibiotic choices for newborn infants.

The acute phase response, as a component of the innate immune system, is part of the first line of defense against invading pathogens. The Stimulator of Interferon Genes (STING) pathway initiates innate immune responses upon recognition of exogenous bacterial and viral DNA. However, whether STING signaling pathway plays any roles in regulating acute phase response during bacterial infection remains unknown. In this study, we used STING-deficient (Tmem173gt) and wildtype mice to investigate acute phase responses to bacterial infection (Escherichia coli, E. coli) and test the effect of exogenous cyclic GMP-AMP (cGAMP, a STING agonist) treatment. Bacterial infection of STING-deficient mice resulted in an increase in mortality and bacterial dissemination. Also, inflammation-induced acute phase response was drastically reduced in STING-deficient mice, showing significant reduction in expression of cytokine TNF-α and acute phase proteins. In contrast, exogenous cGAMP treatment enhanced inflammation-induced acute phase response by increasing the expression of TNF-α and acute phase proteins. Also, cGAMP accelerated bacterial clearance and improved survival rate of wildtype mice, but not STING-deficient mice. Interestingly, cGAMP treatment mitigated bacterial infection induced liver injury in both wildtype and STING-deficient mice. Further in vitro evidence showed that cGAMP treatment retarded TNF-α-mediated hepatocyte apoptosis, potentially accelerating autophagy. Taken together, our results indicated that cGAMP/STING signaling pathway is critical for organism to initiate blood-borne innate immune-responses to defend bacterial infection, and cGAMP is envisaged as a drug candidate for further clinical trial.

Background: The bacteria, Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), are the main reasons for urinary tract infections (UTIs). This research aimed to investigate the isolation of etiologic agents from patients with UTI; it also investigates the antibiotic resistance activities and incidence of ESBL genes between different clinical separates of uropathogenic E. coli, determining their association with ESBL genes. Methods: The study enrolled 1000 positive growth isolates. The predominant pathogen associated with urinary tract infection, Gram-negative, were the main isolates from UTI patients, including E. coli, K. pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus and Enterococcus faecalis. Results: Among suspicious cases of urinary tract infection, we showed that 15.2% of the patients had UTI, and female patients in the childbearing age group were more affected. 644 E. coli (64.4%) and 322 (32.2%) K. pneumoniae were more isolated. Among 936 (93.6%) ESBL producing bacteria, 614 (61.4 %) E. coli showedhigh resistance to the antibiotics, Cefotaxime (85.7 %), Cefepime (85.7 %), Ciprofloxacin (83.1 %) and Kanamycin (77.9 %). Most ESBL-producing K. pneumoniae were multidrug-resistant (MDR). Nitrofurantoin, gentamycin, and imipenem were the most effective antibiotics for ESBL-producing E. coli isolates. Conclusion: Research shows that high rates of MDR Escherichia coli infections in our hospital were the frequent causes of UTIs. Nitrofurantoin and aminoglycosides were the most beneficial first-line drugs to be prescribed in UTI cases. It is recommended that regular investigations should be carried out on drug resistance in all isolates to formulate helpful antibiotic treatment policies in Iraq. Thus, it is important to determine ESBL prevalence in urine E. coli and K. pneumoniae isolates as it has a great impact on the selection of suitable antibacterial agents. In short, more than half of ESBL producers have Multiple Drug Resistance (MDR).

UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase (LpxC), the zinc metalloenzyme catalyzing the first committed step of lipid A biosynthesis in Gram-negative bacteria, has been a target for antibacterial drug discovery for many years. All inhibitor chemotypes reaching an advanced preclinical stage and clinical phase 1 have contained terminal hydroxamic acid, and none have been successfully advanced due, in part, to safety concerns, including hemodynamic effects. We hypothesized that the safety of LpxC inhibitors could be improved by replacing the terminal hydroxamic acid with a different zinc-binding group. After choosing an N-hydroxyformamide zinc-binding group, we investigated the structure-activity relationship of each part of the inhibitor scaffold with respect to Pseudomonas aeruginosa and Escherichia coli LpxC binding affinity, in vitro antibacterial potency and pharmacological properties. We identified a novel, potency-enhancing hydrophobic binding interaction for an LpxC inhibitor. We demonstrated in vivo efficacy of one compound in a neutropenic mouse E. coli infection model. Another compound was tested in a rat hemodynamic assay and was found to have a hypotensive effect. This result demonstrated that replacing the terminal hydroxamic acid with a different zinc-binding group was insufficient to avoid this previously recognized safety issue with LpxC inhibitors.

Background Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications. Methods We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent. Results There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam. Conclusions All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.

Gut microbiota serves as a critical indicator for gut health during treatment of pathogenic bacterial infection. Both Pulsatilla Decoction (abbreviated to PD, a traditional Chinese medicine compound) and Levofloxacin Hydrochloride (LVX) were known to have therapeutic effects to intestinal infectious disease. However, the changes of gut microbiota after PD or LVX treatment remain unclear. Herein, this work aimed to investigate the changes of intestinal flora after PD or LVX therapy of Escherichia coli infection in rats. Results revealed that PD exhibited a valid therapeutic approach for E. coli infection via the intestinal protection, as well as the inhibited release of IL-8 and ICAM-1. Besides, PD was beneficial to rebuild the gut microbiota via restoring Bacteroidetes spp in the composition of the gut microbiota. Comparatively, LVX treatment promoted the infection and ravaged gut microbiota by significantly decreasing Bacteroidetes and increasing Firmicutes. These findings not only highlight the mechanism of Chinese herbal formula, but extend the application of PD as veterinary medicine, feed additive and pre-mixing agent for improving the production of animal derived foods.

Heat shock protein 27 (HSP27) plays an important role in protecting cells from various stress factors. This study aimed to investigate the function of HSP27 gene and its regulatory mechanism as infected by Escherichia coli (E. coli) at the tissue and cellular levels. Real-time PCR was used to detect the differential expression of HSP27 gene in F18 resistant and sensitive Sutai pigs and the differential expression upon E. coli F18ab, F18ac, K88ac bacterial supernatant, thallus infection and LPS induction in IPEC-J2. In addition, the HSP27 gene overexpression vector was constructed to detect the effect of the HSP27 gene overexpression on the adhesion of E. coli F18 to IPEC-J2, secretion of pro-inflammatory factors, and the expression of the upstream key genes in Mitogen-activated protein kinase (MAPK) pathway. Ribosomal S6 kinase (RSK2) is an important protein in the MAPK pathway. Therefore, the RSK2 gene overexpression vector was constructed and the number of colonies was counted after co-transfection of HSP27 and RSK2 gene. Results revealed that the expression level of HSP27 gene in resistant individuals in 11 tissues was higher than sensitive type. At the cellular level, the relative expression levels of HSP27 gene were increased after F18ab, F18ac bacterial supernatant, F18ab thallus infection, and LPS induction for 4 h (P 0.01). The adhesion ability of E. coli F18ab to IPEC-J2 was significantly reduced after HSP27 gene overexpression (P 0.01), and the concentration of pro-inflammatory factors in the HSP27 gene overexpression group was significantly reduced compared with the control group after F18ab infection (P 0.05). Furthermore, the expression of RSK2 was significantly increased in HSP27 overexpression group upon F18ab infection (P 0.01). The colonies quantitative results also showed that the number of colonies was significantly reduced after co-transfection of HSP27 and RSK2 gene. We indicated that the high expression of HSP27 gene may resist the inflammatory response caused by exogenous stress and enhance the ability of IPEC-J2 to resist E. coli F18 infection. RSK2 gene in the MAPK pathway may cooperate with HSP27 gene to participate in the immune response of the organism, which provides a theoretical basis for the study of the mechanism of anti-E. coli infection in piglets.

The German cockroach, Blatella germanica (L.), is a suspected vector of several enteric bacterial pathogens, including Escherichia coli, among livestock and humans. However, little is known about the factors that influence bacterial transmission by cockroaches. Here, we orally infected B. germanica with various laboratory and field strains of E. coli and examined bacterial titers over time to shed new light on the factors that influence the dynamics of infection. Our results reveal that a laboratory strain of E. coli is largely cleared within 48 h while one field isolate can persist in a majority of cockroaches (80–100%) for longer than 3 d with minimal impact on cockroach longevity. We also find that the ability to clear some strains of E. coli is greater in cockroach nymphs than adults. Notably, no differential expression of the antimicrobial gene lysozyme was observed between nymphs and adults or in infected groups. However, clearance of E. coli was significantly reduced in gnotobiotic cockroaches that were reared in the absence of environmental bacteria, suggesting a protective role for the microbiota against exogenous bacterial pathogens. Together, these results demonstrate that the interactions between cockroaches and enteric bacterial pathogens are highly dynamic and influenced by a combination of microbial, host, and environmental parameters. Such factors may affect the disease transmission capacity of cockroaches in nature and should be further considered in both lab and field studies.

Background: Shigatoxin (Stx)-producing Escherichia coli (STEC) are the most common causes of hemolytic uremic syndrome (STEC-HUS). The aim of our study is to compare the risk of developing STEC-HUS in relation to the type of Stx genes (Stx1, Stx2, or both). Methods: This is a prospective, observational, multicenter study involving 63 pediatric units in Northern Italy (ItalKid-HUS Network). STEC-infected children were identified within a screening program for bloody diarrhea during a 10-year period (2010–2019). Stx genes were detected by reverse dot blot or real-time PCR. After the identification of STEC infection, children were followed until diarrhea complete recovery for the possible development of STEC-HUS. Results: Of the 214 Stx-positive patients, 34 (15.9%) developed STEC-HUS. The risk of HUS in STEC-infected children with Stx1 (n: 62; 29.0%) and Stx2 (n: 97; 45.3%) was respectively 0% and 23.7%, while in patients carrying both Stx1 and Stx2 (n: 55; 25.7%), the risk was 12.7% (p: 0.001). Conclusions: Our data confirm that Stx1 is a very rare cause of STEC-HUS and demonstrate that the risk of STEC-HUS halves in the case of Stx1+2-producing Escherichia coli infection compared with infections where Stx2 is present alone. This observation is helpful in assessing the risk of individual STEC-infected patients for the development of HUS and suggests that Stx1, in the presence of Stx2, might exert a protective role possibly by receptor competition.

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a critical concern worldwide. In Italy, CPE isolates are very frequent, with the KPC enzyme types strongly predominant whereas the New Delhi metallo-β-lactamase (NDM) enzymes are extremely rare. Here we report the first detection of NDM-5-producing Escherichia coli sequence type 167 (ST167) isolates from two patients with urinary tract infection (Ec001 and Ec002 from urines), including one with colonisation (Ec003 from faeces) admitted to the same hospital 2 months apart in 2017. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. The carbapenemase type was identified both by phenotypic and genotypic methods. Isolate genotypes were investigated by phylogenetic typing, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Next-generation sequencing (NGS) was used to obtain complete sequences of plasmids. The three E. coli isolates carried the blaNDM-5 gene, shared the same resistance phenotype and belonged to ST167. By PFGE, isolates showed the same profile, suggesting that they were the same strain. NGS revealed that the blaNDM-5 gene was located on a 99-kb multireplicon plasmid (designed pNDM-5-IT) with a peculiar scaffold constituted by four replicons of the IncF type (FIA, FIB and two copies of the FII replicon). pNDM-5-IT plasmid harboured multiple resistance and virulence determinants, including the arginine deaminase (ADI) cluster never found associated with plasmids before. Since NDM-5-producing E. coli ST167 has been regarded as a successful epidemic clone in China, the emergence of such a clone carrying a plasmid associated both with multiresistance and virulence could be a public-health threat.

Intestinal perforation is an uncommon complication and presentation of verocytotoxigenic Escherichia coli (VTEC) infection in individuals with Prader-Willi syndrome (PWS). The common site of perforation from VTEC infection is in the colon (and almost exclusively in the pediatric population), whereas PWS is in the stomach. Terminal ileum perforation is uncommon and is not reported in either these 2 conditions. We report a death from terminal ileum perforations in an adult who had PWS and was infected with VTEC. Potential reasons why the perforation occurred at this rare location, rather than in other more common location, in an adult are discussed.

Shiga toxin-producing Escherichia coli (STEC) infects humans by colonizing the large intestine, and causes kidney damage by secreting Shiga toxins (Stxs). The increased secretion of Shiga toxin 2 (Stx2) by some antibiotics, such as ciprofloxacin (CIP), increases the risk of hemolytic–uremic syndrome (HUS), which can be life-threatening. However, previous studies evaluating this relationship have been conflicting, owing to the low frequency of EHEC infection, very small number of patients, and lack of an appropriate animal model. In this study, we developed gut–kidney axis (GKA) on chip for co-culturing gut (Caco-2) and kidney (HKC-8) cells, and observed both STEC O157:H7 (O157) infection and Stx intoxication in the gut and kidney cells on the chip, respectively. Without any antibiotic treatment, O157 killed both gut and kidney cells in GKA on the chip. CIP treatment reduced O157 infection in the gut cells, but increased Stx2-induced damage in the kidney cells, whereas the gentamycin treatment reduced both O157 infection in the gut cells and Stx2-induced damage in the kidney cells. This is the first report to recapitulate a clinically relevant situation, i.e., that CIP treatment causes more damage than gentamicin treatment. These results suggest that GKA on chip is very useful for simultaneous observation of O157 infections and Stx2 poisoning in gut and kidney cells, making it suitable for studying the effects of antibiotics on the risk of HUS.

Escherichia coli (E. coli), a major cause of male genital tract infections, is asymptomatic and may result in male infertility. We have succeeded in isolating and characterizing proteins of E. Pili coli isolates from semen of infertile men who function as adhesin with a molecular weight (MW) 32.2 kDa. This study aims to prove the ability of IgG results adhesion proteins induced pili of E. MW coli 32.2 kDa as opsonin to determine the value of the activity and phagocytic capacity and as an anti- adhesion by calculating the average number of E. coli that attached to human spermatozoa. E. coli infertile men's semen were cultured using standard bacteriology. Peritoneal macrophages were isolated from mice. Spermatozoa from donors were prepared using Sil with Select Plus. IgG was obtained from mice immunized with (1) PBS (control), (2) E. coli pili adhesion protein isolated from infertile men semen with MW of 32.2 kDa and (3) weakened E. coli isolated from infertile men's semen. Phagocytic activity value was determined by counting the number of cells activated macrophage phagocytosis process in 100 cells. Phagocytic capacity value was determined by counting the number of bacteria ingested by 25 macrophages. Anti-adhesion test was done by counting the number of bacteria attached to 100 spermatozoa. The results of this study showed difference (p=0.000) in phagocytic activity and phagocytic capacity (p=0.000) between treatment (1) and (2), and between treatment (1) to (3). However, treatment (2) and (3) did not differ neither in phagocytic activity (p=0.693) nor in phagocytosis capacity (p=0.125). Anti-adhesion test produces difference (p=0.000) in the number of E. coli that attached to human spermatozoa between treatments (1) and treatment (2), and between treatments (1) and (3). The number of E. coli that attached to human spermatozoa between treatment (2) and treatment (3) was not significantly different (p=0.371). In conclusion, IgG from the induction of E. coli pili adhesion protein of infertile men semen isolates with MW of 32.2 kDa can increase phagocytic activity and capacity as well as serve as an anti- adhesion. Thus, IgG from the induction of E. coli pili adhesion protein of infertile men semen isolates with MW of 32.2 kDa is protective against in vitro E. coli infection, so that it can be used as material to prevent male reproductive tract infections due to E. coli.

Although favorable immune responses to low-dose irradiation (LDI) have been observed in normal mice, i.e., a hormesis effect, little is known about the effects of LDI in infectious diseases. In this study, we examined the effects of LDI on mice with sepsis, a severe and often lethal hyperinflammatory response to bacteria. Female C57BL/6 mice were whole-body irradiated with 10cGy 48h before Escherichia coli infection, and survival, bacterial clearance, cytokines, and antioxidants were quantified. LDI pretreatment significantly increased survival from 46.7% in control mice to 75% in mice with sepsis. The bacterial burden was significantly lower in the blood, spleen, and kidney of LDI-treated mice than in those of control septic mice. The levels of pro-inflammatory cytokines, e.g., IL-1β and IL-6, as well as anti-inflammatory IL-10 were markedly reduced in pre-LDI septic mice. Nitric oxide production by peritoneal macrophages was also reduced in pre-LDI septic mice. Immune cells in the spleen increased and Nrf2 and HO-1 were induced in pre-LDI septic mice. LDI stimulates the immune response and minimizes lethality in septic mice via enhanced bacterial clearance and reduced initial proinflammatory responses.

Two studies were performed to assess the efficacy of Lactobacillus plantarum B1 in prevention of pathogenic Escherichia coli K88 gastrointestinal infection in broilers. In an in vitro study, L. plantarum B1 showed resistance to acid and bile and inhibited the growth of E. coli K88. Additionally, L. plantarum B1 exhibited high ability to adhere to broiler embryo ileal epithelium. In an animal trial, 240 broilers at 1 d of age were randomly assigned to one of 4 treatment arms: negative control (NC) broilers fed a basal diet and not challenged; positive control (PC) broilers fed a basal diet and challenged with E. coli K88; L. plantarum (LP) treatment broilers fed a basal diet containing 2 × 109 cfu/kg L. plantarum B1 and challenged with E. coli K88; and antibiotic treatment (Anti) broilers fed a basal diet supplemented with colistin sulfate (20 mg/kg) and challenged with E. coli K88. Broilers fed L. plantarum B1 had greater (P ≤ 0.05) BW than those in the PC treatment on d 14 and 28. Dietary L. plantarum B1 decreased (P < 0.05) E. coli counts in the cecal contents on d 10 and 14, and increased (P < 0.05) cecal lactic acid bacteria (LAB) on d 8, 10, 14, and 28 compared with the PC treatment. Dietary supplementation of L. plantarum B1 increased (P < 0.05) the ileal mucosal secretory IgA concentration and reduced (P < 0.05) IL-2, IL-4, IFN-γ, and tumor necrosis factor-α levels in the ileum. Overall, these results suggest dietary supplementation of L. plantarum B1 promotes growth performance, lowers cecal E. coli counts, and increases the population of cecal LAB, as well as improves intestinal mucosal immunity in E. coli K88-challenged broilers.

// Bing-Xiu Guo 1 , Qian-Qian Wang 1, 2 , Jia-Hui Li 1, 2 , Zhen-Shun Gan 1 , Xiao-Feng Zhang 3 , Yi-Zhen Wang 1, 2 and Hua-Hua Du 1, 2 1 College of Animal Science, Zhejiang University, Hangzhou, 310058, China 2 Key Laboratory of Animal Nutrition and Feed Science, Eastern of China, Ministry of Agriculture, Zhejiang University, Hangzhou, 310058, China 3 Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China Correspondence to: Hua-Hua Du, email: huahuadu@zju.edu.cn Keywords: lipocalin 2, siderophore, Escherichia coli K88, iron sequestration, intestinal infection Received: May 10, 2017 Accepted: June 05, 2017 Published: June 16, 2017 ABSTRACT Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli ( E. coli ). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism. In this study, we showed that iron was sequestrated within cells in a piglet model of E. coli K88 infection. Siderophores was produced following E. coli K88 infection and siderophore-related genes expression was upregulated in iron-deficiency environment in vitro . Meanwhile, we found that Lcn2 expression was rapidly and robustly induced in jejunum by E. coli K88 infection and could be stimulated by IL-17 and IL-22. Furthermore, both Lcn2 induced in epithelial cells IPEC-1 and added exogenously as a recombinant protein could inhibit the growth of E. coli . We can conclude that Lcn2 is a crucial component of mucosal immune defense against intestinal infection with E. coli K88.

Drosophila have served as a model for research on innate immunity for decades. However, knowledge of the post-transcriptional regulation of immune gene expression by microRNAs (miRNAs) remains rudimentary. In the present study, using small RNA-seq and bioinformatics analysis, we identified 67 differentially expressed miRNAs in Drosophila infected with Escherichia coli compared to injured flies at three time-points. Furthermore, we found that 21 of these miRNAs were potentially involved in the regulation of Imd pathway-related genes. Strikingly, based on UAS-miRNAs line screening and Dual-luciferase assay, we identified that miR-9a and miR-981 could both negatively regulate Drosophila antibacterial defenses and decrease the level of the antibacterial peptide, Diptericin. Taken together, these data support the involvement of miRNAs in the regulation of the Drosophila Imd pathway.

The present study was conducted on 81 commercial broiler chicken farms aged (1-45 days) located in five different centers at Qena province (Qena, Qift, Deshna, Qus and Nag-Hammadi), For bacteriological examination, Samples were taken from diseased and freshly dead chickens (liver; lung; intestine; trachea; nasal cavity; kidneys; yolk sacs; pericardium; and air sacs). The results revealed that 50 out of 600 samples (8.3%) were positive for E. coli isolation, where 30 isolates (9.0%) from 332 baby chicks (up to one week), 20 isolates (7.4%) from 268 broilers (from one week to 6 weeks) were positive for E. coli isolation. Thirty-seven seogroups of E. coli were obtained by serological identification (O1, O6, O8, O20, O26, O27, O44, O86a, O115, O125, O128, O136, O146, O152, O158, O159, O164, O166, O167,O168 and O169) represented as 4 strains were serotyped O27 (8%), 3 strains O44 (6%), 3 strains O125 (6%), 3 strains O152 (6%), 3 strains O159 (6%), 2 strains O1 (4%), 2 strains O6 (4%), 2 strains O20 (4%), 2 strains O26 (4%), 2 strains O166 (4%), 1 strain for each of O8, O86a, O115, O128, O136 ,O146, O158, O164, O167, O168, O169 with (2%) for each of them and 13 isolates were untyped (26%) by the available antisera. Multiplex PCR showed that ompA virulence gene was detected in all serogroups except O8. Moreover, papC virulence gene was detected in all serogroups except O8, O86a, O136, O146, O167 and O169. While Stx2 virulence gene was detected only in serotypes O27 & O125. The eaeA gene was amplified in serogroups O1, O20, O26, O115, O152, O166, O168 and O169. Finally, tsh virulence gene was detected in all serogroups except O20, O26, O86a, O115, O128, O167 and O169.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a highly diverse pathotype of E. coli which colonizes the intestine, and it is considered an important etiological agent associated with bacteremia and other systemic infections, among them urinary tract infection. Retrospective studies evaluating morbidity and mortality of nondomestic felids have demonstrated that urinary tract diseases are among the main causes of death for geriatric animals. Also, mesenchymal neoplasms of the uterus are common in wild felids, and they possess variable morphologic characteristics related to invasiveness and malignancy. This report describes a case of bilateral pyelonephritis due to extraintestinal uropathogenic E. coli infection in a captive jaguar (Panthera onca). The diagnosis was confirmed through pathological, bacterial and immunohistochemical findings. According to molecular analysis, this E. coli strain was classified in the phylogroup F, possessing the following virulence-associated genes: usp, cnf-1, hlyA, papC and sfa. Additionally, this E. coli was highly resistant to β-lactams and first-generation cephalosporin. This jaguar also presented a uterine leiomyoma with distinct distribution, and severe degenerative articular disease, both of them described as frequently seen lesions in geriatric animals from the Panthera genus. RESUMO: Escherichia coli extraintestinal patogênica (ExPEC) é um patotipo altamente diverso de E. coli que coloniza o intestino e é considerada um agente etiológico importante, associado com bacteremia e outras infecções sistêmicas, dentre elas infecções do trato urinário. Estudos retrospectivos avaliando morbidade e mortalidade de felídeos não domésticos demostram que doenças do trato urinário estão entre as principais causas de morte de animais geriátricos. Ainda, neoplasias mesenquimais uterinas são comuns em felídeos de cativeiro e possuem características morfológicas variáveis relacionadas a invasividade e malignidade. Neste relato é descrito um caso de pielonefrite bilateral por E. coli extraintestinal uropatogênica em uma onça-pintada de cativeiro (Panthera onca). O diagnóstico foi confirmado através dos achados patológicos, bacteriológicos e imuno-histoquímicos. A partir da análise molecular, esta cepa de E. coli foi classificada no filogrupo F, possuindo os seguintes genes associados a virulência: usp, cnf-1, hlyA, papC and sfa. Adicionalmente, a bactéria isolada foi altamente resistente a β-lactâmicos e cefalosporinas de primeira geração. Foi observado ainda um leiomioma uterino com distribuição distinta e doença articular degenerativa severa, ambas descritas na literatura como comumente observadas em animais geriátricos do gênero Panthera.

In order to explore the harm caused by Escherichia coli infection to puerperium, and to propose effective and feasible treatment plan, 68 women who are born in hospital and have Escherichia coli infection during puerperium are selected as research objects. According to different treatment methods, they are divided into observation group and experimental group, with 34 cases in each group. The observation group is treated with levofloxacin hydrochloride. The experimental group is treated with cefazolin and levofloxacin hydrochloride. The time of disappearance, adverse reactions and clinical efficacy are compared between the two groups. Studies have found that women infected with Escherichia coli during puerperal period can cause uterine tenderness, anal pain, abnormal lochia, breast tenderness, etc., and timely anti-infective treatment is needed. The total effective rate of maternal treatment in the experimental group is 94.1%, and the total effective rate of maternal treatment in the observation group is 70.6%. The difference between the two groups is statistically significant (P < 0.05). The disappearance time of lower abdominal pain, anal pain and abnormal lochia in the experimental group is shorter than that in the observation group, and the difference is statistically significant (P < 0.05). The incidence of adverse reactions in the experimental group is 8.8%, which is significantly lower than that in the control group (35.3%). The difference is statistically significant (P < 0.05). The effect of cefazolin combined with levofloxacin hydrochloride on the maternal treatment of Escherichia coli in the puerperium period is significant. The clinical symptoms of the patients are obviously improved, and the adverse reactions are less, which is worthy of clinical application.