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Zeitschrift Fur Naturforschung. C,... Jun 2024is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CHCl/MeOH (1:1) roots extract of...
is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CHCl/MeOH (1:1) roots extract of afforded seven compounds namely; β-sitosterol (), stigmasterol (), 6a, 12a-dehydro-deguelin (), tephrosin (), maackiain (), obovatin () and 6-oxo, 6a, 12a-dehydro-deguelin (). GC-MS analysis of essential oils from the root of displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CHCl/MeOH (1:1) extract, MeOH extract, maackiain () and obovatin () showed moderate inhibitory activity against with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 μg/mL). 6a, 12a-dihydro-deguelin (), and 6-oxo, 6a, 12a-dehydro-deguelin () displayed significant activity against with MIC values of 0.66 mg/mL. Tephrosin () and maackiain () also showed moderate antibacterial activity against and with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 μg/mL). The radical scavenging activity results indicated that tephrosin (), obovatin () and 6-oxo, 6a, 12a-dehydro-deguelin () showed potent DPPH scavenging activity with IC values of 10.97, 10.43 and 10.73 μg/mL, respectively, compared to ascorbic acid (IC of 5.83 μg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin () displayed the best binding energy of -8.1 kcal/mol towards pyruvate kinase of (PDB ID: 3T07) and -7.9 kcal/mol towards urease (PDB ID: 1E9Y) and DNA gyrase B of (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to -8.0 kcal/mol). Maackiain () and obovatin () displayed the minimum binding energy of -7.9 and -8.2 kcal/mol towards the LasR protein of (PDB: ID 2UV) and FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (-) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of .
PubMed: 38865441
DOI: 10.1515/znc-2024-0044 -
Acute and Critical Care May 2024Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high...
Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like Herpes Simplex and Varicella Zoster, and fungi-like Candida spp. appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result.
PubMed: 38863352
DOI: 10.4266/acc.2023.01571 -
Skin Health and Disease Jun 2024Incontinence Associated Dermatitis (IAD) is a type of skin inflammation caused by chronic exposure to urine and/or faeces. Current treatment strategies involve creating...
BACKGROUND
Incontinence Associated Dermatitis (IAD) is a type of skin inflammation caused by chronic exposure to urine and/or faeces. Current treatment strategies involve creating a barrier between the skin and urine/faeces rather than targeting specific irritants. Urease expressing pathogens catalyse the conversion of urea, present in urine, into ammonia. The accumulation of ammonia causes an elevation in skin pH which is believed to activate faecal enzymes which damage skin, and opportunistic pathogens, which lead to secondary infections.
OBJECTIVES
To develop a better, multi-factorial model of IAD pathogenesis, including the effect of urease-expressing bacteria on skin, mechanism of damage of urease and urease-triggered activity of faecal enzymes and secondary pathogens. To study the effect of urease inhibition on preventing IAD skin damage.
METHODS
Five separate studies were made using ex vivo porcine skin and in vivo human skin models. Measurements of the change in skin barrier function were made using skin impedance, trans-epidermal water loss (TEWL), stratum corneum moisture and pH. Skin was exposed to artificial urine, inoculated with various microbes, enzymes and chemicals to examine the influence of: 1) urease-positive 2) ammonia, 3) combination of and a faecal enzyme, trypsin, 4) combination of and opportunistic pathogens, and , 5) inhibition of urease using acetohydroxamic acid (AHA) on barrier function.
RESULTS
The urease-mediated production of ammonia had two principal effects: it elevated skin pH and caused inflammation, leading to significant breakdown in skin (stratum corneum) barrier function. Urease was found to further increase the activity of faecal enzymes and opportunistic pathogens, due to elevated skin pH. The urease inhibitor, AHA, was shown to have significantly reduced damage to skin barrier function, measured as its electrical resistance.
CONCLUSIONS
Targeted therapeutic strategies should be developed to prevent the manifestation of IAD, rather than creating a generic barrier between skin and urine/faeces. Urease has been identified as a crucial component in the manifestation of IAD, due to its role in the production of ammonia. Urease inhibition provides a promising therapeutic target to halt the progression of IAD.
PubMed: 38846694
DOI: 10.1002/ski2.349 -
Pakistan Journal of Biological Sciences... Apr 2024<b>Background and Objective:</b> Urinary tract infections from the use of an indwelling urinary catheter are one of the most common infections caused by...
<b>Background and Objective:</b> Urinary tract infections from the use of an indwelling urinary catheter are one of the most common infections caused by <i>Proteus mirabilis</i>. Due to their biofilm-producing capacity and the increasing antimicrobial resistance in this microorganism, this study aimed to determine the prevalence, biofilm-producing capacity, antimicrobial resistance patterns, multidrug resistance and plasmid mediated resistance of the recovered isolates. <b>Materials and Methods:</b> A total of 50 urinary samples were collected from May to August, 2018 from patients on indwelling urinary catheters. Using routine microbiological and biochemical methods, 37 <i>P. mirabilis</i> were isolated. Biofilm forming capability was determined among the isolates using the tube method while antimicrobial susceptibility and plasmid curing were also performed. <b>Results:</b> All isolates were biofilm producers with 17(46%) being moderate producers while 20(54%) were strong biofilm formers. The study isolates exhibited a high resistance rate to empiric antibiotics, including ceftazidime (75.8%), cefuroxime (54.5%), ampicillin (69.7%) and amoxicillin-clavulanic acid (51.5%). Low resistance was seen in the fluoroquinolones, gentamicin and nitrofurantoin. Plasmid curing experiment revealed that most isolates lost their resistance indicating that resistance was borne on plasmids. Plasmid carriage is likely the reason for the high MDR rate of 56.8% observed. <b>Conclusion:</b> These findings necessitate the provision of infection control programs which will guide and implement policies.
Topics: Biofilms; Proteus mirabilis; Catheters, Indwelling; Humans; Anti-Bacterial Agents; Microbial Sensitivity Tests; Urinary Tract Infections; Plasmids; Urinary Catheters; Drug Resistance, Bacterial; Proteus Infections; Catheter-Related Infections; Female; Male; Drug Resistance, Multiple, Bacterial
PubMed: 38840467
DOI: 10.3923/pjbs.2024.268.275 -
Pakistan Journal of Medical Sciences 2024Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to...
OBJECTIVE
Our objective was to quantify the number of various bacteria that frequently cause UTI in diabetes patients as well as to gauge their susceptibility and resistance to antibiotics.
METHOD
A cross-sectional study was conducted at the Internal Medicine Ward of Lady Reading Hospital, Peshawar, Pakistan from June 2021 to December 2021, Patients with confirmed diabetes were included in the study; however, participants receiving antimicrobial medications for a maximum of 14 days were excluded from the study. Resistance of was asssessed using ciprofloxac, ceftazidime and meropenem.
RESULTS
The findings highlighted the the prevalence of in 38.8% of patients, Candida in 19% of patients, in 11.8% of patients, Pseudomonas in 10%, Klebsiella in 9.5% patients, 6.2% patients and Staphylococcus was found in 5.2% patients. According to the overall sensitivity and resistance of antibiotics in microorganisms, Meropenem showed 89.6% sensitivity and 10.4% resistance. Ciprofloxacin showed 38.9% sensitivity and 61.1% resistance and ceftazidime showed 22.7 sensitivity and 77.3% resistance.
CONCLUSION
UTIs were very common in diabetes patients, and was the most common uropathogen found. Compared to male patients, more female patients had infections. The uropathogens showed a significant degree of resistance to ceftizidime and ciprofloxacin.
PubMed: 38827869
DOI: 10.12669/pjms.40.5.8275 -
Heliyon May 2024The ability of ureolytic bacteria to break down stable urea to alkaline ammonia leads to several environmental and health challenges. Ureolytic bacteria such as and...
Synergistic inhibition of ureolytic activity and growth of suggests cobinding of fluoride and acetohydroxamic acid at the urease active site and provides a novel strategy to combat ureolytic bacteria.
The ability of ureolytic bacteria to break down stable urea to alkaline ammonia leads to several environmental and health challenges. Ureolytic bacteria such as and can become pathogenic and cause persistent infections that can be difficult to treat. Inhibiting urease activity can reduce the growth and pathogenicity of ureolytic bacteria. In the present study, we investigated the synergistic effects of tannic acid (TA) and the urease inhibitors fluoride (F) and acetohydroxamic acid (AHA). The concentration of AHA needed for efficient inhibition of the ureolytic activity of can be significantly reduced if AHA is coapplied with tannic acid and sodium fluoride (NaF). Thus, only 1.20 μmol l AHA in combination with 0.30 mmol l tannic acid and 0.60 mmol l NaF delayed the onset of ureolytic pH increase by 95.8 % and increased the growth lag phase by 124.3 % relative to untreated . At these concentrations, without AHA, TA and NaF increased the onset of the ureolytic pH change by only 37.0 % and the growth lag phase by 52.5 %. The strong inhibition obtained with low concentrations of AHA in triple-compound treatments suggests cobinding of F and AHA at the urease active site and could reduce the side effects of AHA when it is employed as a drug against e.g. urinary tract infections (UTIs) and blocked catheters. This study reports the basis for a promising novel therapeutic strategy to combat infections caused by ureolytic bacteria and the formation of urinary tract stones and crystalline biofilms on catheters.
PubMed: 38826744
DOI: 10.1016/j.heliyon.2024.e31209 -
European Journal of Clinical... Jun 2024This study compared the results of the new Sysmex PA-100 AST System, a point-of-care analyser, with routine microbiology for the detection of urinary tract infections...
PURPOSE
This study compared the results of the new Sysmex PA-100 AST System, a point-of-care analyser, with routine microbiology for the detection of urinary tract infections (UTI) and performance of antimicrobial susceptibility tests (AST) directly from urine.
METHODS
Native urine samples from 278 female patients with suspected uncomplicated UTI were tested in the Sysmex PA-100 and with reference methods of routine microbiology: urine culture for bacteriuria and disc diffusion for AST.
RESULTS
The analyser delivered bacteriuria results in 15 min and AST results within 45 min. Sensitivity and specificity for detection of microbiologically confirmed bacteriuria were 84.0% (89/106; 95% CI: 75.6-90.4%) and 99.4% (155/156; 95% CI: 96.5-100%), respectively, for bacterial species within the analyser specifications. These are Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus, which are common species causing uncomplicated UTI. Overall categorical agreement (OCA) for AST results for the five antimicrobials tested in the Sysmex PA-100 (amoxicillin/clavulanic acid, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim) ranged from 85.4% (70/82; 95%CI: 75.9-92.2%) for ciprofloxacin to 96.4% (81/84; 95% CI: 89.9-99.3%) for trimethoprim. The Sysmex PA-100 provided an optimal treatment recommendation in 218/278 cases (78.4%), against 162/278 (58.3%) of clinical decisions.
CONCLUSION
This first clinical evaluation of the Sysmex PA-100 in a near-patient setting demonstrated that the analyser delivers phenotypic AST results within 45 min, which could enable rapid initiation of the correct targeted treatment with no further adjustment needed. The Sysmex PA-100 has the potential to significantly reduce ineffective or unnecessary antibiotic prescription in patients with UTI symptoms.
PubMed: 38825624
DOI: 10.1007/s10096-024-04862-3 -
Protein Expression and Purification Sep 2024Chiral amino acids and their deamination products, α-keto acids, have important applications in food, medicine, and fine chemicals. In this study, two l-amino acid...
Chiral amino acids and their deamination products, α-keto acids, have important applications in food, medicine, and fine chemicals. In this study, two l-amino acid deaminase genes from Proteus mirabilis, PM473 of type Ⅰ and PM471 of type Ⅱ were cloned and expressed in Escherichia coli respectively, expected to achieve the chiral separation of amino acids. Extensive substrate preference testing showed that both deaminases had catalytic effects on the d-amino acid component of the D, l-amino acids, and PM473 has a wider catalytic range for amino acids. When D, L-Cys was used as the substrate, all L-Cys components and 75.1 % of D-Cys were converted to mercapto pyruvate, and the remaining D-Cys was a single chiral enantiomer. Molecular docking analysis showed that the interaction between the substrate and the key residues affected the stereoselectivity of enzymes. The compatibility of hydrophobicity between the binding pocket and substrate may be the basic factor that affects the substrate selectivity. This work provides an alternative method for the production of α-keto acids and the resolution of chiral amino acids.
Topics: Proteus mirabilis; Keto Acids; Molecular Docking Simulation; Escherichia coli; Stereoisomerism; Substrate Specificity; Amino Acids; Bacterial Proteins; Recombinant Proteins; Cloning, Molecular
PubMed: 38821452
DOI: 10.1016/j.pep.2024.106518 -
PloS One 2024Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings....
Uro-pathogens: Multidrug resistance and associated factors of community-acquired UTI among HIV patients attending antiretroviral therapy in Dessie Comprehensive Specialized Hospital, Northeast Ethiopia.
BACKGROUND
Urinary tract infections are common bacterial and fungal infections in humans, occurring both in the community and in immunocompromised patients in healthcare settings. Urinary tract infections have a significant health impact on HIV-infected patients. Nowadays, drug-resistant pathogens are widespread poses a serious clinical risk, and causes urinary tract infection. The common agents of bacteria and fungi that cause urinary tract infection are Escherichia coli followed by Klebsiella pneumonia, Staphylococcus saprophyticus, Enterococcus faecalis, group B streptococcus, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida. albicans. This study aimed to investigate uro-pathogen, multidrug resistance pattern of bacteria, and associated factors of community-acquired urinary tract infection among HIV-positive patients attending antiretroviral therapy in Dessie comprehensive specialized hospital, Northeast Ethiopia from February 1, 2021, to March 30, 2021.
METHODS
An institutional-based cross-sectional study was conducted at Dessie Comprehensive Specialized Hospital. Socio-demographic and clinical data were collected by using structured questionnaires from HIV patients suspected of community-acquired urinary tract infections. About 10 ml of clean-catch midstream urine was collected and inoculated into Blood agar, MacConkey, and Cysteine lactose electrolyte deficient media. Yeasts were identified by using Gram stain, germ tube test, carbohydrate fermentation, assimilation tests, and chromogenic medium. Gram stain and biochemical tests were performed to identify isolates and an antimicrobial susceptibility pattern was performed on disc diffusion techniques. Data were entered and analyzed using SPSS version 25. Both bivariate and multivariable logistic regression analysis was performed and a P value of < 0.05 with an adjusted odds ratio with their 95% confidence interval (CI) was used as statistically significant associations.
RESULTS
From the total 346 study participants, 92 (26.6%) were culture positive 75 (81.52%) were bacterial and 17 (18.48%) were fungal pathogens. From a total of 75 bacteria isolates 51(68%) were Gram-negative bacteria and the most commonly isolated bacteria were E. coli 16 (21.33%) followed by K. pneumoniae 11(14.67%) and enterococcus species 10(10.87. Of the 17 fungal isolates of fungi, 8(47.1%) were represented by C. tropicalis. Of the isolated bacteria, 61(81.3%) were resistant to three and above classes of antibiotics (drug classes). About 13 (81.3%) of E. coli, 9(81.8%) of K. pneumoniae, 8(80%) of Enterococcus species, 7 (77.8%) of P. aeruginosa, and CoNs 7(87.5%) were the most frequently exhibited three and above classes of antibiotics (multi-drug resistance). Amikacin and gentamicin were effective against Gram-negative Uro-pathogens. Participants aged>44year, female, being daily labor, being farmer, unable to read and write, patients with CD4 count of ≤ 200 cells/mm3 and CD4 count of 201-350 cells/mm3, who had chronic diabetics, patients having a history of hospitalization and who had urgency of urinations were statistically significant association with significant urinary tract infections.
CONCLUSION
The burden of community-acquired urinary tract infections among HIV patients is alarmingly increased. Therefore, behavior change communications might be considered for promoting the health status of HIV patients. Moreover, CD4 level monitoring and therapeutics selection based on microbiological culture are quite advisable for the management of urinary tract infections of HIV patients.
Topics: Humans; Ethiopia; Urinary Tract Infections; Female; Male; HIV Infections; Adult; Community-Acquired Infections; Middle Aged; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Young Adult; Microbial Sensitivity Tests; Anti-Bacterial Agents; Hospitals, Special; Bacteria
PubMed: 38820330
DOI: 10.1371/journal.pone.0296480 -
RSC Advances May 2024The antibacterial efficacy of some newly developed C-3 carboxylic group-containing ciprofloxacin-linked 1,2,3-triazole conjugates was studied. Twenty-one compounds from...
Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitors - and -based studies.
The antibacterial efficacy of some newly developed C-3 carboxylic group-containing ciprofloxacin-linked 1,2,3-triazole conjugates was studied. Twenty-one compounds from three different series of triazoles were synthesized using click chemistry and evaluated for their antibacterial activity against nine different pathogenic strains, including three Gram-positive strains, (ATCC29212), (ATCC25923), (clinical isolate), and six Gram-negative bacterial strains, (ATCC25922), (ATCC27853), (clinical isolate), (clinical isolate), (clinical isolate) and (clinical isolate). Among the compounds, 10, 10a, 10b, 10c, 10d, 11a, 11f, 12c, 12e and 12f showed excellent activity with MIC values upto 12.5 μg mL, whereas the control ciprofloxacin showed MIC values of 0.781-25 μg mL towards various strains. In addition, the low toxicity profile of the synthesized molecules revealed that they are potent antibiotics. Molecular docking and MD analysis were performed using the protein structure of DNA gyrase B, which was further corroborated with an assay to evaluate the inhibition of DNA gyrase. The analysis revealed that compound 10b was the most potent inhibitor of DNA gyrase compared to ciprofloxacin, which was employed as the positive control. Furthermore, the structure of two title compounds (11a and 12d) was characterized using single-crystal analysis.
PubMed: 38818013
DOI: 10.1039/d4ra01332h