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1.
PLoS One ; 19(5): e0296109, 2024.
Article En | MEDLINE | ID: mdl-38743696

Colistin resistance is a global concern warning for a one health approach to combat the challenge. Colistin resistant E. coli and their resistance determinants are widely distributed in the environment, and rats could be a potential source of these isolates and resistant determinants to a diverse environmental setting. This study was aimed to determine the presence of colistin resistant E. coli (CREC) in wild rats, their antimicrobial resistance (AMR) phenotypes, and genotypic analysis of mcr-1 CREC through whole genome sequencing (WGS). A total of 39 rats were examined and CREC was isolated from their fecal pellets onto MacConkey agar containing colistin sulfate (1 µg/ mL). AMR of the CREC was determined by disc diffusion and broth microdilution was employed to determine MIC to colistin sulfate. CREC were screened for mcr genes (mcr-1 to mcr-8) and phylogenetic grouping by PCR. Finally, WGS of one mcr-1 CREC was performed to explore its genetic characteristics especially resistomes and virulence determinants. 43.59% of the rats carried CREC with one (2.56%) of them carrying CREC with mcr-1 gene among the mcr genes examined. Examination of seventeen (17) isolates from the CREC positive rats (n = 17) revealed that majority of them belonging to the pathogenic phylogroup D (52.94%) and B2 (11.76%). 58.82% of the CREC were MDR on disc diffusion test. Shockingly, the mcr-1 CREC showed phenotypic resistance to 16 antimicrobials of 8 different classes and carried the ARGs in its genome. The mcr-1 gene was located on a 60 kb IncI2 plasmid. On the other hand, ARGs related to aminoglycosides, phenicols, sulfonamides, tetracyclines and trimethoprims were located on a 288 kb mega-plasmid separately. The mcr-1 CREC carried 58 virulence genes including genes related to adhesion, colonization, biofilm formation, hemolysis and immune-evasion. The isolate belonged to ST224 and closely related to E. coli from different sources including UPEC clinical isolates from human based on cgMLST analysis. The current research indicates that rats might be a possible source of CREC, and the presence of mcr-1 and other ARGs on plasmid increases the risk of ARGs spreading and endangering human health and other environmental components through this infamous pest.


Anti-Bacterial Agents , Colistin , Drug Resistance, Bacterial , Escherichia coli Proteins , Escherichia coli , Microbial Sensitivity Tests , Animals , Colistin/pharmacology , Escherichia coli/genetics , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Rats , Escherichia coli Proteins/genetics , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Bangladesh , Whole Genome Sequencing/methods , Phylogeny , Escherichia coli Infections/microbiology , Escherichia coli Infections/veterinary , Escherichia coli Infections/drug therapy , Animals, Wild/microbiology , Feces/microbiology
2.
Sci Rep ; 14(1): 11053, 2024 05 14.
Article En | MEDLINE | ID: mdl-38744900

This study investigated the influence of polyunsaturated fatty acid composition and vitamin E supplementation on oxidative status and immune responses in weanling piglets pre- and post-E. coli challenge. Suckling piglets (n = 24) were randomly selected from two litters for an oral supplementation (1 mL/day) with fish oil or hemp oil and vitamin E supplementation (60 mg natural vitamin E/mL oil) from day 10 to 28 of age. At day 29 and 30 of age, each piglet was orally inoculated with 6.7 × 108 and 3.96 × 108 CFU of F4 and F18 E. coli, respectively. Blood was sampled from all piglets on day 28 before E. coli challenge and on day 35 of age to investigate immunological and oxidative stress markers in plasma. One week after weaning and exposure to E. coli, a general reduction in the α-tocopherol concentration and activity of GPX1 was obtained. Vitamin E supplementation lowered the extent of lipid peroxidation and improved the antioxidative status and immune responses after E. coli challenge. Hemp oil had the greatest effect on antioxidant enzyme activity. Provision of hemp oil and vitamin E to suckling piglets may reduce the incidence of post-weaning diarrhea.


Cannabis , Dietary Supplements , Escherichia coli Infections , Escherichia coli , Fish Oils , Oxidation-Reduction , Vitamin E , Animals , Vitamin E/pharmacology , Swine , Fish Oils/pharmacology , Fish Oils/administration & dosage , Cannabis/chemistry , Oxidation-Reduction/drug effects , Escherichia coli Infections/immunology , Escherichia coli Infections/veterinary , Escherichia coli Infections/drug therapy , Escherichia coli Infections/prevention & control , Antioxidants/pharmacology , Antioxidants/metabolism , Oxidative Stress/drug effects , Weaning , Lipid Peroxidation/drug effects , Swine Diseases/microbiology , Swine Diseases/immunology , Swine Diseases/prevention & control , Swine Diseases/drug therapy
3.
Sci Rep ; 14(1): 10196, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702355

Urinary tract infections (UTIs) are the most common bacterial infections and uropathogenic Escherichia coli (UPEC) is the main etiological agent of UTIs. UPEC can persist in bladder cells protected by immunological defenses and antibiotics and intracellular behavior leads to difficulty in eradicating the infection. The aim of this paper is to design, prepare and characterize surfactant-based nanocarriers (niosomes) able to entrap antimicrobial drug and potentially to delivery and release antibiotics into UPEC-infected cells. In order to validate the proposed drug delivery system, gentamicin, was chosen as "active model drug" due to its poor cellular penetration. The niosomes physical-chemical characterization was performed combining different techniques: Dynamic Light Scattering Fluorescence Spectroscopy, Transmission Electron Microscopy. Empty and loaded niosomes were characterized in terms of size, ζ-potential, bilayer features and stability. Moreover, Gentamicin entrapped amount was evaluated, and the release study was also carried out. In addition, the effect of empty and loaded niosomes was studied on the invasion ability of UPEC strains in T24 bladder cell monolayers by Gentamicin Protection Assay and Confocal Microscopy. The observed decrease in UPEC invasion rate leads us to hypothesize a release of antibiotic from niosomes inside the cells. The optimization of the proposed drug delivery system could represent a promising strategy to significatively enhance the internalization of antimicrobial drugs.


Anti-Bacterial Agents , Gentamicins , Liposomes , Uropathogenic Escherichia coli , Gentamicins/pharmacology , Uropathogenic Escherichia coli/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Drug Carriers/chemistry , Urinary Tract Infections/microbiology , Urinary Tract Infections/drug therapy , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Drug Delivery Systems , Microbial Sensitivity Tests
4.
Microbiologyopen ; 13(3): e1411, 2024 Jun.
Article En | MEDLINE | ID: mdl-38706434

Traditional bacteriocin screening methods often face limitations due to diffusion-related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion-related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell-free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S-07-4, and SK-106-1). The inhibition of the CFS by proteinase K suggested that the antimicrobial activity was proteinaceous in nature, potentially bacteriocins. The activity of E. coli PUTS 58 and SK-106-1 was enhanced in an artificial urine medium, with both inhibiting all eight UPECs. A putative microcin H47 operon was identified in E. coli SK-106-1, along with a previously identified microcin V and colicin E7 in E. coli PUTS 37 and PUTS 58, respectively. These findings indicate that ABU bacteriocin-producers could serve as viable prophylactics and therapeutics in the face of increasing antibiotic resistance among uropathogens.


Bacteriuria , Escherichia coli Infections , Uropathogenic Escherichia coli , Uropathogenic Escherichia coli/drug effects , Uropathogenic Escherichia coli/genetics , Bacteriuria/microbiology , Humans , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Bacteriocins/pharmacology , Bacteriocins/genetics , Nephelometry and Turbidimetry , Biological Assay/methods , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Urinary Tract Infections/microbiology
5.
Cell Biochem Funct ; 42(4): e4026, 2024 Jun.
Article En | MEDLINE | ID: mdl-38693631

This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.


Cholecalciferol , Escherichia coli Infections , Escherichia coli , Gamma Rays , Animals , Mice , Cholecalciferol/pharmacology , Male , Escherichia coli Infections/drug therapy , Escherichia coli Infections/pathology , Liver/pathology , Liver/drug effects , Liver/metabolism , Lung/pathology , Lung/metabolism , Cytokines/metabolism , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Aspartate Aminotransferases/blood
6.
Front Public Health ; 12: 1364664, 2024.
Article En | MEDLINE | ID: mdl-38699424

Asymptomatic long-term carriers of Shigatoxin producing Escherichia coli (STEC) are regarded as potential source of STEC-transmission. The prevention of outbreaks via onward spread of STEC is a public health priority. Accordingly, health authorities are imposing far-reaching restrictions on asymptomatic STEC carriers in many countries. Various STEC strains may cause severe hemorrhagic colitis complicated by life-threatening hemolytic uremic syndrome (HUS), while many endemic strains have never been associated with HUS. Even though antibiotics are generally discouraged in acute diarrheal STEC infection, decolonization with short-course azithromycin appears effective and safe in long-term shedders of various pathogenic strains. However, most endemic STEC-strains have a low pathogenicity and would most likely neither warrant antibiotic decolonization therapy nor justify social exclusion policies. A risk-adapted individualized strategy might strongly attenuate the socio-economic burden and has recently been proposed by national health authorities in some European countries. This, however, mandates clarification of strain-specific pathogenicity, of the risk of human-to-human infection as well as scientific evidence of social restrictions. Moreover, placebo-controlled prospective interventions on efficacy and safety of, e.g., azithromycin for decolonization in asymptomatic long-term STEC-carriers are reasonable. In the present community case study, we report new observations in long-term shedding of various STEC strains and review the current evidence in favor of risk-adjusted concepts.


Anti-Bacterial Agents , Azithromycin , Escherichia coli Infections , Shiga-Toxigenic Escherichia coli , Humans , Escherichia coli Infections/drug therapy , Azithromycin/therapeutic use , Azithromycin/administration & dosage , Anti-Bacterial Agents/therapeutic use , Carrier State/drug therapy , Hemolytic-Uremic Syndrome/microbiology
7.
Biomacromolecules ; 25(5): 3112-3121, 2024 May 13.
Article En | MEDLINE | ID: mdl-38651274

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 µg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed ß-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.


Anti-Bacterial Agents , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Escherichia coli/drug effects , Animals , Microbial Sensitivity Tests , Polyelectrolytes/chemistry , Polyelectrolytes/pharmacology , Peptides/chemistry , Peptides/pharmacology , Protein Conformation, alpha-Helical , Micelles , Escherichia coli Infections/drug therapy , Hemolysis/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Mice , Polyglutamic Acid/chemistry , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/pharmacology , Humans
8.
Mol Biol Rep ; 51(1): 566, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38656625

BACKGROUND: Escherichia coli is the most common etiological agent of urinary tract infections (UTIs). Meanwhile, plasmid-mediated quinolone resistance (PMQR) is reported in E. coli isolates producing extended-spectrum ß-lactamases (ESBLs). Furthermore, the reservoirs and mechanisms of acquisition of uropathogenic Escherichia coli (UPEC) strains are poorly understood. On the other hand, UTIs are common in pregnant women and the treatment challenge is alarming. METHODS AND RESULTS: In the present study, 54 pregnant women with acute cystitis were included. A total of 108 E. coli isolates, 54 isolates from UTI and 54 isolates from faeces of pregnant women (same host) were collected. In the antimicrobial susceptibility test, the highest rate of antibiotic resistance was to nalidixic acid (77%, 83/108) and the lowest rate was to imipenem (9%, 10/108). Among the isolates, 44% (48/108) were ESBLs producers. A high frequency of PMQR genes was observed in the isolates. The frequency of PMQR genes qnrS, qnrB, aac(6')-Ib-cr, and qnrA was 58% (63/108), 21% (23/108), 9% (10/108), and 4% (4/108), respectively. Meanwhile, PMQR genes were not detected in 24% (20/85) of isolates resistant to nalidixic acid and/or fluoroquinolone, indicating that other mechanisms, i.e. chromosomal mutations, are involved in resistance to quinolones, which were not detected in the present study. In ESBL-producing isolates, the frequency of PMQR genes was higher than that of non-ESBL-producing isolates (81% vs. 53%). Meanwhile, UTI and faeces isolates mainly belonged to phylogenetic group B2 (36/54, 67% and 25/54, 46%, respectively) compared to other phylogenetic groups. In addition, virulence factors and multidrug-resistant (MDR) were mainly associated with phylogenetic group B2. However, predominant clones in faeces were not found in UTIs. Rep-PCR revealed the presence of 85 clones in patients. Among the clones, 40 clones were detected only in faeces (faeces-only), 35 clones only in UTI (UTI-only) and 10 clones in both faeces and UTI (faeces-UTI). We found that out of 10 faeces-UTI clones, 5 clones were present in the host's faeces flora. CONCLUSION: This study revealed a high rate of resistance to the quinolone nalidixic acid and a widespread distribution of PMQR genes in MDR E. coli strains producing ESBLs. The strains represented virulence factors and phylogenetic group B2 are closely associated with abundance in UTI and faeces. However, the predominant clones in faeces were not found in UTIs and it is possible that rep-PCR is not sufficiently discriminating clones.


Anti-Bacterial Agents , Cystitis , Escherichia coli Infections , Escherichia coli , Feces , Microbial Sensitivity Tests , Plasmids , Quinolones , beta-Lactamases , Humans , Female , beta-Lactamases/genetics , Plasmids/genetics , Feces/microbiology , Quinolones/pharmacology , Pregnancy , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli/drug effects , Adult , Anti-Bacterial Agents/pharmacology , Cystitis/microbiology , Drug Resistance, Bacterial/genetics , Prevalence , Urinary Tract Infections/microbiology , Nalidixic Acid/pharmacology
9.
Front Cell Infect Microbiol ; 14: 1387497, 2024.
Article En | MEDLINE | ID: mdl-38638826

The dissemination of antibiotic resistance in Escherichia coli poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse mechanisms employed by E. coli in developing resistance to antibiotics. We primarily focus on pathotypes of E. coli (e.g., uropathogenic E. coli) and investigate the genetic determinants and molecular pathways that confer resistance, shedding light on both well-characterized and recently discovered mechanisms. The most prevalent mechanism continues to be the acquisition of resistance genes through horizontal gene transfer, facilitated by mobile genetic elements such as plasmids and transposons. We discuss the role of extended-spectrum ß-lactamases (ESBLs) and carbapenemases in conferring resistance to ß-lactam antibiotics, which remain vital in clinical practice. The review covers the key resistant mechanisms, including: 1) Efflux pumps and porin mutations that mediate resistance to a broad spectrum of antibiotics, including fluoroquinolones and aminoglycosides; 2) adaptive strategies employed by E. coli, including biofilm formation, persister cell formation, and the activation of stress response systems, to withstand antibiotic pressure; and 3) the role of regulatory systems in coordinating resistance mechanisms, providing insights into potential targets for therapeutic interventions. Understanding the intricate network of antibiotic resistance mechanisms in E. coli is crucial for the development of effective strategies to combat this growing public health crisis. By clarifying these mechanisms, we aim to pave the way for the design of innovative therapeutic approaches and the implementation of prudent antibiotic stewardship practices to preserve the efficacy of current antibiotics and ensure a sustainable future for healthcare.


Escherichia coli Infections , Escherichia coli , Humans , Escherichia coli/genetics , Escherichia coli Infections/drug therapy , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , beta-Lactamases/genetics , Drug Resistance, Microbial
11.
Mol Biol Rep ; 51(1): 509, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38622237

BACKGROUND: The main causes of hospital- and community-acquired urinary tract infections (UTIs) are a group of Escherichia coli (E. coli) strains with multiple virulence factors known as uropathogenic E. coli. METHODS AND RESULTS: One hundred E. coli isolates from the urine specimens of hospital- and community-acquired UTI patients were characterized based on their virulence factors and genetic relatedness using PCR and RAPD‒PCR, respectively. Among all, the traT (71%), sitA (64%), ompT (54%), malX (49%), ibeA (44%), tsh (39%), hlyD (18%) and cnf1 (12%) genes had the highest to lowest frequencies, respectively. There was no significant difference between the frequency of tested virulence genes in E. coli isolates from inpatients and outpatients. The frequency of the hlyD gene was significantly greater in E. coli isolates from patients hospitalized in gynecology, dermatology and intensive care unit (ICU) wards than in those from other wards. Eight virulence gene patterns were common among the isolates of inpatients in different wards of the same hospital, of which five patterns belonged to the isolates of inpatients in the same ward. More E. coli isolates with similar virulence gene patterns and greater genetic similarity were found in female patients than in male patients. The analysis of the RAPD‒PCR dendrograms revealed more genetic similarities among the E. coli isolates from inpatients than among those from outpatients. CONCLUSION: Our findings indicate the presence of a wide variety of virulence factors in E. coli isolates and the possibility of spreading the same clones in different wards of the hospital.


Escherichia coli Infections , Urinary Tract Infections , Uropathogenic Escherichia coli , Humans , Male , Female , Escherichia coli Infections/drug therapy , Virulence/genetics , Random Amplified Polymorphic DNA Technique , Urinary Tract Infections/drug therapy , Hospitals , Molecular Typing , Virulence Factors/genetics , Uropathogenic Escherichia coli/genetics , Anti-Bacterial Agents/therapeutic use
12.
BMC Med Genomics ; 17(1): 110, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671498

BACKGROUND: Escherichia coli is known to cause about 2 million deaths annually of which diarrhea infection is leading and typically occurs in children under 5 years old. Although Africa is the most affected region there is little information on their pathotypes diversity and their antimicrobial resistance. OBJECTIVE: To determine the pathotype diversity and antimicrobial resistance among E. coli from patients attending regional referral hospitals in Tanzania. MATERIALS AND METHODS: A retrospective cross-section laboratory-based study where a total of 138 archived E. coli isolates collected from 2020 to 2021 from selected regional referral hospitals in Tanzania were sequenced using the Illumina Nextseq550 sequencer platform. Analysis of the sequences was done in the CGE tool for the identification of resistance genes and virulence genes. SPSS version 20 was used to summarize data using frequency and proportion. RESULTS: Among all 138 sequenced E. coli isolates, the most prevalent observed pathotype virulence genes were of extraintestinal E. coli UPEC fyuA gene 82.6% (114/138) and NMEC irp gene 81.9% (113/138). Most of the E. coli pathotypes observed exist as a hybrid due to gene overlapping, the most prevalent pathotypes observed were NMEC/UPEC hybrid 29.7% (41/138), NMEC/UPEC/EAEC hybrid 26.1% (36/138), NMEC/UPEC/DAEC hybrid 18.1% (25/138) and EAEC 15.2% (21/138). Overall most E. coli carried resistance gene to ampicillin 90.6% (125/138), trimethoprim 85.5% (118/138), tetracycline 79.9% (110/138), ciprofloxacin 76.1% (105/138) and 72.5% (100/138) Nalidixic acid. Hybrid pathotypes were more resistant than non-hybrid pathotypes. CONCLUSION: Whole genome sequencing reveals the presence of hybrid pathotypes with increased drug resistance among E. coli isolated from regional referral hospitals in Tanzania.


Escherichia coli Infections , Escherichia coli , Tanzania , Humans , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli/drug effects , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Drug Resistance, Bacterial/genetics , Retrospective Studies , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Referral and Consultation , Virulence Factors/genetics
13.
Biomolecules ; 14(4)2024 Apr 08.
Article En | MEDLINE | ID: mdl-38672469

Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a pathogenic bacterium that causes huge economic losses to the pig farming industry and considerably threatens human health. The quorum sensing (QS) system plays a crucial role in the survival and pathogenesis of pathogenic bacteria. Hence, it is a viable approach to prevent ExPEC infection by compromising the QS system, particularly the LuxS/AI-2 system. In this study, we investigated the effects of baicalin on the LuxS/AI-2 system of ExPEC. Baicalin at concentrations of 25, 50, and 100 µg/mL significantly diminished the survival ability of ExPEC in hostile environments and could inhibit the biofilm formation and autoagglutination ability in ExPEC. Moreover, baicalin dose-dependently decreased the production of AI-2 and down-regulated the expression level of luxS in PCN033. These results suggest that baicalin can weaken the virulence of PCN033 by inhibiting the LuxS/AI-2 system. After the gene luxS was deleted, AI-2 production in PCN033 was almost completely eliminated, similar to the effect of baicalin on the production of AI-2 in PCN033. This indicates that baicalin reduced the production of AI-2 by inhibiting the expression level of luxS in ExPEC. In addition, the animal experiment further showed the potential of baicalin as a LuxS/AI-2 system inhibitor to prevent ExPEC infection. This study highlights the potential of baicalin as a natural quorum-sensing inhibitor for therapeutic applications in preventing ExPEC infection by targeting the LuxS/AI-2 system.


Bacterial Proteins , Carbon-Sulfur Lyases , Extraintestinal Pathogenic Escherichia coli , Flavonoids , Homoserine , Homoserine/analogs & derivatives , Quorum Sensing , Quorum Sensing/drug effects , Flavonoids/pharmacology , Animals , Carbon-Sulfur Lyases/genetics , Carbon-Sulfur Lyases/metabolism , Swine , Virulence/drug effects , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Homoserine/metabolism , Extraintestinal Pathogenic Escherichia coli/drug effects , Extraintestinal Pathogenic Escherichia coli/pathogenicity , Extraintestinal Pathogenic Escherichia coli/genetics , Biofilms/drug effects , Biofilms/growth & development , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Lactones/pharmacology , Gene Expression Regulation, Bacterial/drug effects , Swine Diseases/microbiology , Swine Diseases/drug therapy
14.
PLoS One ; 19(4): e0300596, 2024.
Article En | MEDLINE | ID: mdl-38578750

INTRODUCTION: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are pathogens of significant public health interest for which new antibiotics are urgently needed. AIM: To determine the prevalence of ESBLs in E. coli and K. pneumoniae isolates from patients attending the Tamale Teaching Hospital (TTH) in Ghana. METHODOLOGY: The study was a cross-sectional study involving convenience sampling of E. coli and K. pneumoniae isolates from consenting patients' clinical specimens, between April and June 2015. Antimicrobial susceptibility test was performed, and ESBL-producer phenotypes were further screened for BlaTEM, BlaSHV, and BlaCTX-M genes. Patients' clinical data were additionally collected using a structured questionnaire. RESULTS: Of the 150 non-duplicate E. coli and K. pneumoniae isolates identified, 140 were confirmed as E. coli (84%, n = 117) and K. pneumoniae (16%, n = 23). Of these, sixty-two (44%) [E. coli (84%; n = 52); K. pneumoniae (16%; n = 10)] phenotypically expressed ESBLs. The proportion of ESBL-producing isolates was higher in adults (15-65 years) than in neonates (< 28 days) (p = 0.14). Most of the isolates showed a high percentage resistance to ampicillin (96%) and tetracycline (89%), but a relatively lower resistance to amikacin (36%). No isolate was resistant to meropenem. More ESBL producers were multidrug resistant compared to non-ESBL-producers [23% (14/62) versus 18% (14/78); p = 0.573]. Overall, 74% (n = 46) of the ESBL genotypes expressed BlaCTX-M-1 genes, followed by 63% (n = 39) BlaTEM, and 16% (n = 10) BlaSHV. The study showed a high prevalence of ESBL-positive E. coli and K. pneumoniae, mostly CTX-M-1 producers at TTH. CONCLUSION: Routine laboratory ESBL screening is warranted to inform patient management.


Escherichia coli Infections , Klebsiella Infections , Adult , Infant, Newborn , Humans , Escherichia coli/genetics , Klebsiella pneumoniae/genetics , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli Infections/genetics , Cross-Sectional Studies , Ghana/epidemiology , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella Infections/genetics , beta-Lactamases/genetics , Anti-Bacterial Agents/pharmacology , Hospitals, Teaching , Microbial Sensitivity Tests
15.
Surg Infect (Larchmt) ; 25(3): 247-252, 2024 Apr.
Article En | MEDLINE | ID: mdl-38588519

Background: The prevalence of community-onset infections of extended spectrum ß-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.


Escherichia coli Infections , Klebsiella Infections , Pneumonia , Humans , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Retrospective Studies , beta-Lactamases , Escherichia coli , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella pneumoniae , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Risk Factors , Klebsiella , Surgical Wound Infection/drug therapy , Surgical Wound Infection/epidemiology
16.
Clin Med (Lond) ; 24(2): 100036, 2024 Mar.
Article En | MEDLINE | ID: mdl-38588916

A 76-year-old Malay female presented with 2 days history of fever and vomiting. She was found to have Escherichia coli and Klebsiella pneumoniae bacteraemia with no clear intra-abdominal cause on the initial computed tomography of the abdomen and pelvis (CTAP). She clinically improved with 2 weeks duration of intravenous meropenem. She subsequently developed septic shock and a repeated CTAP demonstrated increased hepatic parenchymal density with extensive parenchymal calcifications. Curvilinear calcifications were seen in the paraspinal and pelvic musculature.


Calcinosis , Humans , Female , Aged , Calcinosis/diagnostic imaging , Sepsis/microbiology , Tomography, X-Ray Computed , Liver Diseases/diagnostic imaging , Klebsiella pneumoniae/isolation & purification , Klebsiella Infections/diagnosis , Klebsiella Infections/complications , Klebsiella Infections/drug therapy , Escherichia coli Infections/complications , Escherichia coli Infections/diagnosis , Escherichia coli Infections/drug therapy , Muscular Diseases/diagnostic imaging , Anti-Bacterial Agents/therapeutic use , Meropenem/therapeutic use , Meropenem/administration & dosage
17.
Int J Biol Macromol ; 267(Pt 2): 131389, 2024 May.
Article En | MEDLINE | ID: mdl-38582461

This work developed Acer tegmentosum extract-mediated silver nanoparticles (AgNPs) loaded chitosan (CS)/alginic acid (AL) scaffolds (CS/AL-AgNPs) to enhance the healing of E. coli-infected wounds. The SEM-EDS and XRD results revealed the successful formation of the CS/AL-AgNPs. FTIR analysis evidenced that the anionic group of AL (-COO-) and cationic amine groups of CS (-NH3+) were ionically crosslinked to form scaffold (CS/AL). The CS/AL-AgNPs exhibited significant antimicrobial activity against both Gram-positive (G+) and Gram-negative (G-) bacterial pathogens, while being non-toxic to red blood cells (RBCs), the hen's egg chorioallantoic membrane (HET-CAM), and a non-cancerous cell line (NIH3T3). Treatment with CS/AL-AgNPs significantly accelerated the healing of E. coli-infected wounds by regulating the collagen deposition and blood parameters as evidenced by in vivo experiments. Overall, these findings suggest that CS/AL-AgNPs are promising for the treatment of infected wounds.


Acer , Alginates , Anti-Bacterial Agents , Chitosan , Escherichia coli , Metal Nanoparticles , Plant Extracts , Silver , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , Animals , Wound Healing/drug effects , Escherichia coli/drug effects , Mice , Acer/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , NIH 3T3 Cells , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alginates/chemistry , Alginates/pharmacology , Escherichia coli Infections/drug therapy , Tissue Scaffolds/chemistry
18.
Gut Microbes ; 16(1): 2347021, 2024.
Article En | MEDLINE | ID: mdl-38685762

Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.


Amoxicillin , Drug Resistance, Multiple, Bacterial , Escherichia coli , Feces , Gastrointestinal Microbiome , Inulin , Pantoprazole , Animals , Inulin/pharmacology , Inulin/metabolism , Mice , Gastrointestinal Microbiome/drug effects , Escherichia coli/drug effects , Escherichia coli/genetics , Feces/microbiology , Amoxicillin/pharmacology , Pantoprazole/pharmacology , beta-Lactamases/metabolism , beta-Lactamases/genetics , Dysbiosis/microbiology , Dysbiosis/drug therapy , Anti-Bacterial Agents/pharmacology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Female , Prebiotics/administration & dosage
19.
Emerg Infect Dis ; 30(5): 974-983, 2024 May.
Article En | MEDLINE | ID: mdl-38666612

We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.


Anti-Bacterial Agents , Bacteremia , Community-Acquired Infections , Escherichia coli Infections , Escherichia coli , Klebsiella , Recurrence , Staphylococcal Infections , Staphylococcus aureus , Humans , Bacteremia/microbiology , Bacteremia/epidemiology , Klebsiella/drug effects , Klebsiella/genetics , Male , Risk Factors , Escherichia coli/drug effects , Female , Community-Acquired Infections/microbiology , Community-Acquired Infections/epidemiology , Middle Aged , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella Infections/drug therapy , Drug Resistance, Bacterial , Adult , France/epidemiology
20.
Front Cell Infect Microbiol ; 14: 1301351, 2024.
Article En | MEDLINE | ID: mdl-38655284

Bacterial infections emerge as a significant contributor to mortality and morbidity worldwide. Emerging extended-spectrum ß-lactamase (ESBL) Escherichia coli strains provide a greater risk of bacteremia and mortality, are increasingly resistant to antibiotics, and are a major producer of ESBLs. E. coli bacteremia-linked mastitis is one of the most common bacterial diseases in animals, which can affect the quality of the milk and damage organ functions. There is an elevated menace of treatment failure and recurrence of E. coli bacteremia necessitating the adoption of rigorous alternative treatment approaches. In this study, Se-Boil-CuO multimetallic nanoparticles (MMNPs) were synthesized as an alternate treatment from Talaromyces haitouensis extract, and their efficiency in treating ESBL E. coli was confirmed using standard antimicrobial assays. Scanning electron microscopy, UV-visible spectroscopy, and dynamic light scattering were used to validate and characterize the mycosynthesized Se-BiO-CuO MMNPs. UV-visible spectra of Se-BiO-CuO MMNPs showed absorption peak bands at 570, 376, and 290 nm, respectively. The average diameters of the amorphous-shaped Se-BiO-CuO MMNPs synthesized by T. haitouensis extract were approximately 66-80 nm, respectively. Se-BiO-CuO MMNPs (100 µg/mL) showed a maximal inhibition zone of 18.33 ± 0.57 mm against E. coli. Se-BiO-CuO MMNPs also exhibited a deleterious impact on E. coli killing kinetics, biofilm formation, swimming motility, efflux of cellular components, and membrane integrity. The hemolysis assay also confirms the biocompatibility of Se-BiO-CuO MMNPs at the minimum inhibitory concentration (MIC) range. Our findings suggest that Se-BiO-CuO MMNPs may serve as a potential substitute for ESBL E. coli bacteremia.


Anti-Bacterial Agents , Copper , Escherichia coli , Microbial Sensitivity Tests , beta-Lactamases , Escherichia coli/drug effects , beta-Lactamases/metabolism , Animals , Copper/chemistry , Copper/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Metal Nanoparticles/chemistry , Escherichia coli Infections/drug therapy , Escherichia coli Infections/microbiology , Nanoparticles/chemistry
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