-
Frontiers in Cellular and Infection... 2024, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in...
, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in multidrug-resistant (MDR) strains. This upsurge calls for innovative approaches in infection control, beyond traditional antibiotics. Our research introduces bacteriophage (phage) therapy as a novel non-antibiotic strategy to combat these drug-resistant infections. We isolated P2-71, a lytic phage derived from canine feces, demonstrating potent activity against MDR strains. P2-71 showcases a notably brief 10-minute latent period and a significant burst size of 228 particles per infected bacterium, ensuring rapid bacterial clearance. The phage maintains stability over a broad temperature range of 30-50°C and within a pH spectrum of 4-11, highlighting its resilience in various environmental conditions. Our host range assessment solidifies its potential against diverse MDR strains. Through killing curve analysis, P2-71's effectiveness was validated at various MOI levels against 37, highlighting its versatility. We extended our research to examine P2-71's stability and bactericidal kinetics in artificial urine, affirming its potential for clinical application. A detailed genomic analysis reveals P2-71's complex genetic makeup, including genes essential for morphogenesis, lysis, and DNA modification, which are crucial for its therapeutic action. This study not only furthers the understanding of phage therapy as a promising non-antibiotic antimicrobial but also underscores its critical role in combating emerging MDR infections in both veterinary and public health contexts.
Topics: Animals; Dogs; Anti-Bacterial Agents; Bacteriophage P2; Proteus mirabilis; Biofilms; Bacteriophages
PubMed: 38500503
DOI: 10.3389/fcimb.2024.1347173 -
Food Research International (Ottawa,... Aug 2023Hawaijar, ethnic vegan fermented soybean food of Manipur, India is culturally and gastronomically important indigenously produced food. It is alkaline, sticky,... (Review)
Review
Hawaijar, ethnic vegan fermented soybean food of Manipur, India is culturally and gastronomically important indigenously produced food. It is alkaline, sticky, mucilaginous and slightly pungent and bears similar properties with many fermented soybean foods of Southeast Asia like natto of Japan, douchi of China, thua nao of Thailand, choongkook jang of Korea. The functional microorganism is Bacillus and has numerous health benefits like fibrinolytic enzyme, antioxidant, antidiabetic, and ACE inhibitory activities. It is also very rich in nutrients but unscrupulous production method and sale lead to food safety issues. Huge potential pathogen population upto the level of 10 cfu/g Bacillus cereus and Proteus mirabilis were detected. Recent studies revealed presence of enterotoxic and urease gene in microorganisms originated from hawaijar. Improved and regulated food chain will result in hygienic and safe hawaijar. It has scope for functional food and nutraceutical global market and hold potential to provide employment to enhance the overall socioeconomic status of the region. Scientific production of fermented soybean over the traditional methods is summarized in this paper along with food safety and health benefits. Microbiological aspects on fermented soybean along with nutritive values are critically explained inside the paper.
Topics: Humans; Vegans; Glycine max; India; Functional Food; Fermented Foods
PubMed: 37316061
DOI: 10.1016/j.foodres.2023.112983 -
Acta Veterinaria Hungarica Apr 2024Proteus mirabilis is a common enteric bacterium in livestock and humans. The increase and spread of the antimicrobial resistant P. mirabilis is considered alarming...
Proteus mirabilis is a common enteric bacterium in livestock and humans. The increase and spread of the antimicrobial resistant P. mirabilis is considered alarming worldwide. Transmission mainly occurs through consumption of contaminated poultry products. We investigated antimicrobial resistance (AMR) and virulence markers in broiler chicken-originated P. mirabilis isolates from 380 fecal samples. Phenotypic AMR test was performed against seventeen different antimicrobials. Genotypic AMR test was performed to detect sixteen different AMR genes. The samples were also tested for the presence of eight different virulence genes and biofilm formation. P. mirabilis was isolated in 11% of the samples, with significantly high multidrug-resistant (MDR) prevalence (63%). All isolates were resistant to tetracycline (100%). The combined disc method indicated that all isolates were of extended-spectrum beta-lactamase (ESBL) producers, which was compatible with the high blaTEM prevalence (95%). This was associated with blaTEM being responsible for more than 80% of ampicillin resistance in enteric pathogens. The absence of phenotypically carbapenem-resistant isolates was compatible with the very low prevalences of blaOXA (2%) and blaNDM (0%). All isolates were positive for pmfA, atfA, hpmA, and zapA (100%) virulence genes, while biofilm formation rate (85%) indicated high adherence abilities of the isolates.
Topics: Humans; Animals; Anti-Bacterial Agents; Virulence; Proteus mirabilis; Chickens; beta-Lactamases; Drug Resistance, Bacterial; Microbial Sensitivity Tests
PubMed: 38578700
DOI: 10.1556/004.2023.00990 -
Frontiers in Cellular and Infection... 2023is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity...
INTRODUCTION
is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg and Ca and formation of crystals. In this study, we showed that -acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation.
METHODS
To quantify urease activity, Berthelot's method was done on bacterial extracts treated with NAC. We also used an catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles.
RESULTS
NAC inhibits urease activity of clinical isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on , and inhibited biofilm formation and catheter occlusion in an . A significant 4-8 reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (>10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and infection by reducing the production of IL-6, IL-8 and IL-1b.
DISCUSSION
Using biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.
Topics: Humans; Urinary Catheterization; Acetylcysteine; Urease; Proteus Infections; Proteus mirabilis; Urinary Tract Infections; Catheters; Inflammation; Anti-Inflammatory Agents; Biofilms
PubMed: 37965267
DOI: 10.3389/fcimb.2023.1216798 -
ACS Omega Oct 2023This study utilized a simple hydrothermal technique to prepare pure BiVO and tightly bound BiVO/multiwalled carbon nanotubes (MWCNTs) nanocomposite materials. The...
This study utilized a simple hydrothermal technique to prepare pure BiVO and tightly bound BiVO/multiwalled carbon nanotubes (MWCNTs) nanocomposite materials. The surfactant was employed to control the growth, size, and assembly of BiVO and the nanocomposite. Various techniques including X-ray diffraction (XRD), Ultraviolet-visible (UV-vis), photoluminescence (PL), Raman, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) were utilized to analyze and characterize BiVO and the BiVO/MWCNTs nanocomposite. Through XRD analysis, it was found that the carbon nanotubes were effectively embedded within the lattice of BiVO without generating any separate impurity phase and had no influence on the BiVO monoclinic structure. TEM images confirmed the presence of MWCNTs within BiVO. Furthermore, adding MWCNTs in the BiVO/MWCNTs nanocomposite resulted in an effective charge transfer transition and improved carrier separation, as evidenced by PL analysis. The introduction of MWCNTs also led to a significant reduction in the optical band gap due to quantum effects. Finally, the antibacterial activity of pure BiVO and the BiVO/MWCNTs nanocomposite was assessed by exposing and to these materials. Biofilm inhibition and antibiofilm activity were measured using a crystal violet assay and a FilmTracer LIVE/DEAD Biofilm Viability Kit. The results demonstrated that pure BiVO and BiVO/MWCNTs effectively inhibited biofilm formation. In conclusion, both pure BiVO and BiVO/MWCNTs are promising materials for inhibiting the bacterial biofilm during bacterial infections.
PubMed: 37841170
DOI: 10.1021/acsomega.3c04722 -
Pathogens (Basel, Switzerland) Jul 2023Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1)...
Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed by the disk diffusion method. Antibiotic-resistance genes for class A beta-lactamases, carbapenemases, and plasmid resistance to colistin resistance () were screened by RT-PCR. (2) Results: The 240 enterobacteria were composed of: (60.83%), (21.67%), (13.75%), (2.08%), (0.83%), (0.42%), and (0.42%). Class A beta-lactamase genes were found in 229 isolates (70.41% , 37.5% , 83.75% , and 0.42% ). The carbapenemase genes and were found in 25 isolates, including 14 isolates with , 13 isolates with , and 2 isolates with both genes simultaneously. The gene was found in one isolate of . (3) Conclusions: The epidemiology of antibiotic-resistance genes in enterobacteria in Senegal shows the emergence of CPEs. This phenomenon is worrying, and rigorous surveillance is necessary to avoid further spread.
PubMed: 37623934
DOI: 10.3390/pathogens12080974 -
Molecular Therapy. Oncology Mar 2024Cancer immunotherapy based on bioengineering of bacteria can effectively increase anticancer immune responses. However, few studies have investigated the antitumor...
Cancer immunotherapy based on bioengineering of bacteria can effectively increase anticancer immune responses. However, few studies have investigated the antitumor potential of engineering . Here, we genetically engineered to overexpress flagellin B (FlaB) protein in a murine CT26 tumor model. We found that a large number of FlaB-expressing colonized tumor tissues, enhanced T cell infiltration and secretion of cytokines and cytotoxic proteins in tumors, and significantly restrained tumor growth. Our results also showed that programmed death ligand 1 (PD-L1) expression in tumor-infiltrating immune cells was elevated after treatment with FlaB-expressing . In addition, combination therapy with FlaB-expressing and PD-L1 blockade synergistically improved antitumor efficacy by enhancing infiltration of CD8 cells. Furthermore, serum liver biochemical indices of mice increased in the short term in both the and the FlaB-expressing treatment groups but gradually recovered in the later stage of treatment so that FlaB protein expression did not increase the toxicity of . Taken together, our results suggest that could serve as an engineered bacterium for bacterium-based cancer immunotherapy.
PubMed: 38596299
DOI: 10.1016/j.omton.2024.200770 -
Journal of Clinical Microbiology Apr 2024Traditionally, cephalothin susceptibility results were used to predict the susceptibility of additional cephalosporins; however, in 2013-2014, the Clinical and... (Review)
Review
Traditionally, cephalothin susceptibility results were used to predict the susceptibility of additional cephalosporins; however, in 2013-2014, the Clinical and Laboratory Standards Institute (CLSI) revisited this practice and determined that cefazolin is a more accurate proxy than cephalothin for uncomplicated urinary tract infections (uUTIs). Therefore, a cefazolin surrogacy breakpoint was established to predict the susceptibility of seven oral cephalosporins for , , and in the context of uUTIs. Clinical microbiology laboratories face several operational challenges when implementing the cefazolin surrogacy breakpoint, which may lead to confusion for the best path forward. Here, we review the historical context and data behind the surrogacy breakpoints, review PK/PD profiles for oral cephalosporins, discuss challenges in deploying the breakpoint, and highlight the limited clinical outcome data in this space.
Topics: Humans; Cefazolin; Cephalosporins; Cephalothin; Anti-Bacterial Agents; Microbial Sensitivity Tests; Urinary Tract Infections; Escherichia coli; Monobactams
PubMed: 38457194
DOI: 10.1128/jcm.00788-21 -
International Wound Journal Apr 2024Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried... (Meta-Analysis)
Meta-Analysis
Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.
Topics: Humans; Diabetic Foot; Escherichia coli; Prevalence; Staphylococcus aureus; Anti-Bacterial Agents; Osteomyelitis; Peripheral Vascular Diseases; Bacterial Infections; Diabetes Mellitus
PubMed: 38619084
DOI: 10.1111/iwj.14864 -
Journal of Microbiological Methods May 2024Bacterial biofilms form when bacteria attach to surfaces and generate an extracellular matrix that embeds and stabilizes a growing community. Detailed visualization and...
Bacterial biofilms form when bacteria attach to surfaces and generate an extracellular matrix that embeds and stabilizes a growing community. Detailed visualization and quantitative analysis of biofilm architecture by optical microscopy are limited by the law of diffraction. Expansion Microscopy (ExM) is a novel Super-Resolution technique where specimens are physically enlarged by a factor of ∼4, prior to observation by conventional fluorescence microscopy. ExM requires homogenization of rigid constituents of biological components by enzymatic digestion. We developed an ExM approach capable of expanding 48-h old Proteus mirabilis biofilms 4.3-fold (termed PmbExM), close to the theoretic maximum expansion factor without gross shape distortions. Our protocol, based on lytic and glycoside-hydrolase enzymatic treatments, degrades rigid components in bacteria and extracellular matrix. Our results prove PmbExM to be a versatile and easy-to-use Super-Resolution approach for enabling studies of P. mirabilis biofilm architecture, assembly, and even intracellular features, such as DNA organization.
Topics: Proteus mirabilis; Biofilms; Bacteria; DNA; Microscopy, Fluorescence
PubMed: 38561125
DOI: 10.1016/j.mimet.2024.106927