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International Journal of Molecular... Jun 2024Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of...
Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even , the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of and by , , , , , and . The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.
Topics: Urinary Tract Infections; Animals; Humans; Mice; Escherichia coli; Female; Cell Extracts; Bacterial Lysates
PubMed: 38892345
DOI: 10.3390/ijms25116157 -
BMC Microbiology Jun 2024This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance...
OBJECTIVE
This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes.
METHODS
The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain.
RESULTS
Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings.
CONCLUSION
This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as bla, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.
Topics: Proteus mirabilis; beta-Lactamases; Humans; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Microbial Sensitivity Tests; Proteus Infections; Whole Genome Sequencing; Bacterial Proteins; Chromosomes, Bacterial; Genome, Bacterial; Carbapenems
PubMed: 38890647
DOI: 10.1186/s12866-024-03365-7 -
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 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 -
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 -
Annals of Clinical Microbiology and... May 2024Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate...
BACKGROUND
Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates.
METHODS
The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR.
RESULTS
Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity.
CONCLUSION
Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.
Topics: Proteus mirabilis; Ciprofloxacin; Biofilms; Microbial Sensitivity Tests; Humans; Anti-Bacterial Agents; Proteus Infections; Virulence Factors; Virulence
PubMed: 38802894
DOI: 10.1186/s12941-024-00704-4 -
Pharmaceutics May 2024is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting...
is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting biological and pharmacological assays is crucial to validate the therapeutic efficacy of this plant within the context of traditional medicine. In the present study, we investigated the biological activity of extracts and fractions obtained from organs against bacteria (, , , , , , and using in vitro models. The precipitate fraction obtained from the frond methanolic extract showed significant antibacterial activity (minimal inhibitory concentration [MIC] 120 µg/mL) against the strain and was effective against both Gram-positive and Gram-negative bacteria. The hexane fraction also obtained from frond methanolic extract, showed a trichomonacidal effect with an IC of 82.8 μg/mL and a low cytotoxic effect. Hsf6 exhibited the highest activity against , and the GC-MS analysis revealed that the predominant compound was 16-pregnenolone. The remaining identified compounds were primarily terpene-type compounds.
PubMed: 38794287
DOI: 10.3390/pharmaceutics16050624