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World Journal of Gastroenterology May 2024The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological...
BACKGROUND
The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.
CASE SUMMARY
A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as and , were more in the patient. Beneficial bacteria such as , , , and were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as , and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms.
CONCLUSION
Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.
Topics: Humans; Female; Middle Aged; Enteritis; Radiation Injuries; Gastrointestinal Microbiome; Fecal Microbiota Transplantation; Uterine Cervical Neoplasms; RNA, Ribosomal, 16S; Treatment Outcome; Chronic Disease; Colonoscopy; Intestines; Feces; Radiotherapy
PubMed: 38817661
DOI: 10.3748/wjg.v30.i19.2603 -
The Journal of Biological Chemistry May 2024Klebsiella pneumoniae provides influential prototypes for lipopolysaccharide O antigen (OPS) biosynthesis in Gram-negative bacteria. Sequences of OPS-biosynthesis gene...
Klebsiella pneumoniae provides influential prototypes for lipopolysaccharide O antigen (OPS) biosynthesis in Gram-negative bacteria. Sequences of OPS-biosynthesis gene clusters in serotypes O4 and O7 suggest fundamental differences in the organization of required enzyme modules compared to other serotypes. Furthermore, some required activities were not assigned by homology shared with characterized enzymes. The goal of this study was therefore to resolve the serotype O4 and O7 pathways, to expand our broader understanding of glycan polymerization and chain termination processes. The O4 and O7 antigens were produced from cloned genetic loci in recombinant Escherichia coli. Systematic in vivo and in vitro approaches were then applied to assign each enzyme in each of the pathways, defining the necessary components for polymerization and chain termination. OPS assembly is accomplished by multiprotein complexes formed by interactions between polymerase components variably distributed in single and multi-module proteins. In each complex, a terminator function is present in a protein containing a characteristic coiled-coil molecular ruler, which determines glycan chain-length. In serotype O4, we discovered a CMP-α-3-deoxy-ᴅ-manno-octulosonic acid (Kdo)-dependent chain-terminating glycosyltransferase that is the founding member of a new glycosyltransferase family (GT137), and potentially identifies a new glycosyltransferase fold. The O7 OPS is terminated by a methylphosphate moiety, like the K. pneumoniae O3 antigen, but the methyltransferase-kinase enzyme pairs responsible for termination in these serotypes differ in sequence and predicted structures. Together, the characterization of O4 and O7 has established unique enzyme activities and provided new insight into glycan-assembly strategies that are widely distributed in bacteria.
PubMed: 38815868
DOI: 10.1016/j.jbc.2024.107420 -
PLoS Biology May 2024The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive...
The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.
Topics: Peptidoglycan; Cell Division; Hydrolysis; Escherichia coli Proteins; Escherichia coli; Adenosine Triphosphate; Cryoelectron Microscopy; Cell Wall; Protein Conformation; Models, Molecular; N-Acetylmuramoyl-L-alanine Amidase; Bacterial Outer Membrane Proteins; ATP-Binding Cassette Transporters; Cystic Fibrosis Transmembrane Conductance Regulator; Lipoproteins; Cell Cycle Proteins
PubMed: 38814940
DOI: 10.1371/journal.pbio.3002628 -
Microbiology Spectrum May 2024Two patients with acute gastroenteritis tested positive for Shiga toxin-producing (STEC) by polymerase chain reaction (PCR), and both strains carried the Shiga toxin 2...
UNLABELLED
Two patients with acute gastroenteritis tested positive for Shiga toxin-producing (STEC) by polymerase chain reaction (PCR), and both strains carried the Shiga toxin 2 encoding gene. Since routine culture using CHROMagar STEC failed to recover these isolates, immunomagnetic separation (IMS) targeting the top six non-O157:H7 serotypes was used for isolate recovery. After two subsequent IMS runs, the STEC strains were isolated from trypticase soy broth with and without overnight enrichment for runs 1 and 2, respectively. Serotyping based on whole-genome sequencing revealed that both patients carried the strain O166:H15 STEC with the gene. Hence, the magnetic beads used in IMS appeared to have cross-reactivity with other serotypes. When the STEC isolates from both stools were cultured on CHROMagar STEC and sheep blood agar (BAP), two distinct colony sizes were apparent after overnight incubation. The small and large colonies were picked and separately cultured on both media, and colony growth was observed for 2 weeks at room temperature after an initial overnight incubation at 37°C. After 1 week, the colonies showed concentric ring structures with a darker center and a lighter surrounding on CHROMagar STEC and a "fried egg"-resembling structure with a raised circular center and a flat surrounding on BAP. Both colony types remained morphologically different on CHROMagar STEC throughout the 15 days. However, on BAP, their appearance was comparable by day 7.
IMPORTANCE
Shiga toxin-producing (STEC) infections can lead to severe complications such as bloody diarrhea and hemolytic uremic syndrome (HUS), especially in young children and the elderly. Strains that carry the shiga toxin 2 gene (), such as O157:H7, have been mostly linked with severe disease outcomes. In recent years, outbreaks caused by non-O157:H7 strains have increased. O166:H15 has been previously reported causing a gastroenteritis outbreak in 1996 as a non-STEC strain, however the O166:H15 serotype we recovered carried the gene. It was particularly challenging to isolate this strain from stools by culture. Consequently, we tested immunomagnetic separation for the STEC recovery, which was a novel approach on clinical stools. Virulence genes were included for the characterization of these isolates.
PubMed: 38814093
DOI: 10.1128/spectrum.00098-24 -
Microbiology Spectrum May 2024The emergence of carbapenem-resistant strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing strains in...
The emergence of carbapenem-resistant strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing strains in Tianjin, China. This study aimed to investigate the risk factors for infections with carbapenem-resistant (CREC) strains. This retrospective case-control study was conducted at a tertiary teaching hospital. A total of 134 CREC clinical isolates were collected from the General Hospital of Tianjin Medical University between 2013 and 2020. The control group was selected at a ratio of 1:1 from patients with nosocomial carbapenem-susceptible infection. Risk factors for nosocomial CREC infection and clinical outcomes were analyzed using univariate and multivariate analyses. Multivariate analysis revealed that cephalosporin exposure (odd ratio OR = 2.01), carbapenem exposure (OR = 1.96), glucocorticoid exposure (OR = 32.45), and surgical history (OR = 3.26) were independent risk factors for CREC infection. The in-hospital mortality rate in the CREC group was 29.1%, and age >65 years (OR = 3.19), carbapenem exposure (OR = 3.54), and central venous catheter insertion (OR = 4.19) were independent risk factors for in-hospital mortality in patients with CREC infections. Several factors were identified in the development of nosocomial CREC infections. The CREC isolates were resistant to most antibiotics. Reducing CREC mortality requires a comprehensive consideration of appropriate antibiotic use, underlying diseases, and invasive procedures.IMPORTANCE is an opportunistic pathogen that causes severe hospital-acquired infections. The spread of carbapenem-resistant is a global threat to public health, and only a few antibiotics are effective against these infections. Consequently, these infections are usually associated with poor prognosis and high mortality. Therefore, understanding the risk factors associated with the causes and outcomes of these infections is crucial to reduce their incidence and initiate appropriate therapies. In our study, several factors were found to be involved in nosocomial carbapenem-resistant (CREC) infections, and CREC isolates were resistant to most antibiotics. Reducing CREC mortality needs a comprehensive consideration of whether antibiotics are used appropriately, underlying diseases, and invasive interventions. These findings provide valuable evidence for the development of anti-infective therapy, infection prevention, and control of CREC-positive infections.
PubMed: 38814065
DOI: 10.1128/spectrum.04228-23 -
EClinicalMedicine May 2024Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI...
BACKGROUND
Urinary tract infections (UTI) affect approximately 250 million people annually worldwide. Patients often experience a cycle of antimicrobial treatment and recurrent UTI (rUTI) that is thought to be facilitated by a gut reservoir of uropathogenic (UPEC).
METHODS
125 patients with UTI caused by an antibiotic-resistant organism (ARO) were enrolled from July 2016 to May 2019 in a longitudinal, multi-center cohort study. Multivariate statistical models were used to assess the relationship between uropathogen colonization and recurrent UTI (rUTI), controlling for clinical characteristics. 644 stool samples and 895 UPEC isolates were interrogated for taxonomic composition, antimicrobial resistance genes, and phenotypic resistance. Cohort UTI gut microbiome profiles were compared against published healthy and UTI reference microbiomes, as well as assessed within-cohort for timepoint- and recurrence-specific differences.
FINDINGS
Risk of rUTI was not independently associated with clinical characteristics. The UTI gut microbiome was distinct from healthy reference microbiomes in both taxonomic composition and antimicrobial resistance gene (ARG) burden, with 11 differentially abundant taxa at the genus level. rUTI and non-rUTI gut microbiomes in the cohort did not generally differ, but gut microbiomes from urinary tract colonized patients were elevated in abundance 7-14 days post-antimicrobial treatment. Corresponding UPEC gut isolates from urinary tract colonizing lineages showed elevated phenotypic resistance against 11 of 23 tested drugs compared to non-colonizing lineages.
INTERPRETATION
The gut microbiome is implicated in UPEC urinary tract colonization during rUTI, serving as an ARG-enriched reservoir for UPEC. UPEC can asymptomatically colonize the gut and urinary tract, and post-antimicrobial blooms of gut among urinary tract colonized patients suggest that cross-habitat migration of UPEC is an important mechanism of rUTI. Thus, treatment duration and UPEC populations in both the urinary and gastrointestinal tract should be considered in treating rUTI and developing novel therapeutics.
FUNDING
This work was supported in part by awards from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.'s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). REDCap is Supported by Clinical and Translational Science Award (CTSA) Grant UL1 TR002345 and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
PubMed: 38813445
DOI: 10.1016/j.eclinm.2024.102490 -
Heliyon May 2024Since the clock of antimicrobial resistance was set, modern medicine has shed light on a new cornerstone in technology to overcome the worldwide dread of the...
Since the clock of antimicrobial resistance was set, modern medicine has shed light on a new cornerstone in technology to overcome the worldwide dread of the post-antimicrobial era. Research organizations are exploring the use of nanotechnology to modify metallic crystals from macro to nanoscale size, demonstrating significant interest in the field of antimicrobials. Herein, the antimicrobial activities of aluminum oxide (AlO), cobalt aluminum oxide (CoAlO), and aluminum doped zinc oxide (ZnAlO) nanoparticles were examined against some nosocomial pathogens. The study confirmed the formation and characterization of AlO, CoAlO, and ZnAlO nanoparticles using various techniques, revealing the generation of pure nanoscale nanoparticles. With inhibition zones ranging from 9 to 14 mm and minimum inhibitory concentrations varying from 4 mg/mL to 16 mg/mL, the produced nanoparticles showed strong antibacterial activity against , , , and . Meanwhile, the bactericidal concentrations ranged from 8 mg/mL to 40 mg/mL. In culture, ZnAlO NPs demonstrated a unique ability to inhibit the development of nosocomial infections with high bactericidal activity (8 mg/mL). Transmission electron microscope images revealed changes in cell shape, bacterial cell wall morphology, cytoplasmic membrane, and protoplasm due to the introduction of tested nanoparticles. These results pave the way for the use of these easily bacterial wall-piercing nanoparticles in combination with potent antibiotics to overcome the majority of bacterial strains' resistance.
PubMed: 38813232
DOI: 10.1016/j.heliyon.2024.e31462 -
Heliyon May 2024The demand for cowhide (ponmo) is currently very high, particularly in Nigeria, due to rising commodity prices, including animal proteins, which has forced a larger...
The demand for cowhide (ponmo) is currently very high, particularly in Nigeria, due to rising commodity prices, including animal proteins, which has forced a larger percentage of the population who cannot afford meat, chicken, turkey or eggs to rely on other meat products such as "ponmo," "kundi," and "tinko" as an alternative source of protein. This research aims to identify microorganisms associated with ponmo, determine the antibiogram of the isolates, and assess the nutritional value of ponmo marketed in Ilishan-Remo central market. Six ponmo vendors were sampled for Dry White Ponmo (DWP), Wet White Ponmo (WWP), Wet Brown Ponmo (WBP) and Brown Ponmo Water (BPW) and transported in sterile containers to the Laboratory for analysis to determine the microbial load, sensitivity, and proximate analysis using standardized methods. For microbiological analysis, samples were tested in triplicate. All samples analyzed had a high microbial load count (from 1.1 x 10 to 1.4 x 10). The organisms isolated were (34.21 %) (26.31 %) spp. (18.42 %) spp. (13.15 %) and Coagulase-negative staphylococci (7.89 %). All the isolates were multidrug-resistant (MDR). Septrin had the highest resistivity (86.84 %) while gentamicin had the lowest resistance (7.89 %). Pefloxacin sensitivity was observed in 37 of the 38 isolates (97.37 % sensitivity). Ciprofloxacin and gentamicin came second and third (84.2 % and 73.68 % sensitivity) respectively. According to the proximate analysis, the WWP has more protein, fat, and fiber, whereas the WBP has more moisture. Food handlers should follow Good Hygiene Practices and take a Food Handlers Test regularly.
PubMed: 38813194
DOI: 10.1016/j.heliyon.2024.e30882 -
Frontiers in Bioengineering and... 2024Protein crystallization as opposed to well-established chromatography processes has the benefits to reduce production costs while reaching a comparable high purity....
Protein crystallization as opposed to well-established chromatography processes has the benefits to reduce production costs while reaching a comparable high purity. However, monitoring crystallization processes remains a challenge as the produced crystals may interfere with analytical measurements. Especially for capturing proteins from complex feedstock containing various impurities, establishing reliable process analytical technology (PAT) to monitor protein crystallization processes can be complicated. In heterogeneous mixtures, important product characteristics can be found by multivariate analysis and chemometrics, thus contributing to the development of a thorough process understanding. In this project, an analytical set-up is established combining offline analytics, on-line ultraviolet visible light (UV/Vis) spectroscopy, and in-line Raman spectroscopy to monitor a stirred-batch crystallization process with multiple phases and species being present. As an example process, the enzyme alcohol dehydrogenase (LADH) was crystallized from clarified Escherichia coli () lysate on a 300 mL scale in five distinct experiments, with the experimental conditions changing in terms of the initial lysate solution preparation method and precipitant concentration. Since UV/Vis spectroscopy is sensitive to particles, a cross-flow filtration (cross-flow filtration)-based bypass enabled the on-line analysis of the liquid phase providing information on the lysate composition regarding the nucleic acid to protein ratio. A principal component analysis (PCA) of Raman spectra supported the identification of spectra and wavenumber ranges associated with productspecific information and revealed that the experiments followed a comparable, spectral trend when crystals were present. Based on preprocessed Raman spectra, a partial least squares (PLS) regression model was optimized to monitor the target molecule concentration in real-time. The off-line sample analysis provided information on the crystal number and crystal geometry by automated image analysis as well as the concentration of ADH and host cell proteins (HCPs) In spite of a complex lysate suspension containing scattering crystals and various impurities, it was possible to monitor the target molecule concentration in a heterogeneous, multi-phase process using spectroscopic methods. With the presented analytical set-up of off-line, particle-sensitive on-line, and in-line analyzers, a crystallization capture process can be characterized better in terms of the geometry, yield, and purity of the crystals.
PubMed: 38812919
DOI: 10.3389/fbioe.2024.1397465 -
Frontiers in Cellular and Infection... 2024Avian colibacillosis (AC), caused by infection with (), is a major threat to poultry health, food safety and public health, and results in high mortality and...
Avian colibacillosis (AC), caused by infection with (), is a major threat to poultry health, food safety and public health, and results in high mortality and significant economic losses. Currently, new drugs are urgently needed to replace antibiotics due to the continuous emergence and increasing resistance of multidrug-resistant (MDR) strains of caused by the irrational use of antibiotics in agriculture and animal husbandry. In recent years, antimicrobial peptides (AMPs), which uniquely evolved to protect the host, have emerged as a leading alternative to antibiotics in clinical settings. CATH-2, a member of the antimicrobial cathelicidin peptide family, has been reported to have antibacterial activity. To enhance the antimicrobial potency and reduce the adverse effects on animals, we designed five novel AMPs, named C2-1, C2-2, C2-3, C2-4 and C2-5, based on chicken CATH-2, the secondary structures of these AMPs were consistently α-helical and had an altered net charge and hydrophobicity compared to those of the CATH-2 (1-15) sequences. Subsequently, the antimicrobial activities of CATH-2 (1-15) and five designed peptides against MDR were evaluated . Specifically, C2-2 showed excellent antimicrobial activity against either the ATCC standard strain or veterinary clinical isolates of MDR , with concentrations ranging from 2-8 g/mL. Furthermore, C2-2 maintained its strong antibacterial efficacy under high temperature and saline conditions, demonstrating significant stability. Similarly, C2-2 retained a high level of safety with no significant hemolytic activity on chicken mature red blood cells or cytotoxicity on chicken kidney cells over the concentration range of 0-64 g/mL. Moreover, the administration of C2-2 improved the survival rate and reduced the bacterial load in the heart, liver and spleen during MDR infection in chickens. Additionally, pathological damage to the heart, liver and intestine was prevented when MDR infected chickens were treated with C2-2. Together, our study showed that C2-2 may be a promising novel therapeutic agent for the treatment of MDR infections and AC.
Topics: Animals; Chickens; Escherichia coli; Escherichia coli Infections; Drug Resistance, Multiple, Bacterial; Poultry Diseases; Anti-Bacterial Agents; Microbial Sensitivity Tests; Antimicrobial Peptides; Antimicrobial Cationic Peptides; Cathelicidins
PubMed: 38812753
DOI: 10.3389/fcimb.2024.1390934