Detection of antifungal drug-resistant and ERG11 gene mutations among clinical isolates of Candida species isolated from Khartoum, Sudan. [version 2; peer review: 2 approved
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ABSTRACT:
SUBMITTER: Osman Mohamed A
PROVIDER: S-EPMC8114185 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe increased prevalence of carbapenem-resistant Gram-negative isolates caused by Metallo-?-lactamase (MBL) is worrisome in clinical settings worldwide. The mortality rate associated with infections caused by MBLs producing organisms ranging from 18 to 67%.This study aimed to determine the prevalence of Metallo-?-lactamase genes among some Gram-negative clinical isolates (Carbapenems susceptible and resistant).MethodsThis paper describes a descriptive cross-sectional study carried out to detect MBL genes such as (blaVIM, blaIMP and blaNDM) by multiplex PCR mixture reaction among 200 Gram-negative clinical isolates (Citrobacter spp, Escherichia coli, Enterobacter spp, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Proteus valgaris). Khartoum hospitals during 2015 to 2016.Limitation: The study organisms were not evaluated for non-MBL carbapenemases, such as KPC and OXA-48.ResultsThe prevalence of MBL genes by multiplex PCR assays among 200 Gram-negative clinical isolates was 72(36.1%). MBL positive genes among 100 carbapenems sensitive and 100 resistant isolates were 27(27%) and 45(45%) respectively. There was a statistically, significant association between the antimicrobial susceptibility and the presences of MBL genes (P.value?=?0.008).E.coli was the predominant species possessing MBL genes 26(36.1%), with 22(30.7%) species having a combination of MBL genes.Verona integron Metallo beta-lactamase (VIM) was the most frequent genes 28(38.9%) out of 72 MBL detected genes, followed by imipenemase (IMP) was 19(26.4%), and consequently, New Delhi Metallo beta lactamase was 3(4.2%).ConclusionThis study revealed a high prevalence of MBL genes in some Gram-negative isolates from Khartoum State Hospitals which were not previously established in these hospitals.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3581-z) contains supplementary material, which is available to authorized users.
| S-EPMC6296134 | biostudies-other
Project description:Abstract Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objective To determine the profile of fluconazole-resistant Candida isolates (FRCS) and the proportion of erg11 gene mutation in fluconazole-resistant C. albicans (FRCA) isolates Methods After getting approval from ethics the study was conducted on 150 isolates of FRCS obtained from patients admitted to our tertiary care hospital from September 2019 to December 2021. All the isolates were revived onto Sabouraud dextrose agar (SDA) and identified by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Fluconazole-resistance was detected by VITEK 2 automated system. Deoxyribonucleic acid (DNA) of FRCA isolates were extracted by QIAamp DNA Mini kit (Qiagen-51 304, Hilden, Germany) as per manufacturer's instruction. A single primer pair targeting the nucleotide sequence from 1067 to 1576 bp region of erg11 gene was used for amplification as per Xu et al. with minor modification and 500 bp polymerase chain reaction (PCR) products were observed by gel electrophoresis. A positive clinical isolate of FRCA was used as a positive control. The PCR products were purified and subjected to Sanger sequencing with an ABI PRISM DNA analyzer (Applied Biosystems) and mutations were detected by using Mega (version 7) software by comparing with the published GenBank sequence AF153844.1 of C. albicans strain ATCC 28516. Categorical variables were expressed in percentages and continuous variables were expressed in mean (average). Results Out of the total of 150 FRCS, the most common fluconazole-resistant agent of candidiasis was C. auris, which was isolated from 60 (40%) cases followed by 24 (16%) isolates of C. glabrata, 19 (12.7%) isolates of C. krusei, 18 (12%) isolates of C. parapsilosis, 17 (11.3%) isolates of C. albicans, 10 (6.7%) isolates of C. tropicalis, and only two (1.3%) isolates of C. guilliermondii. Among these 17 FRCA isolates, 9 isolates were obtained from genital swabs, 5 from blood, and a single isolate each from the perianal swab, ear swab, and sputum. A total of 12 (70.6%) out of 17 FRCA isolates yielded 500 bp region in erg11 gene. Gel electrophoresis image of PCR products of erg11 gene is depicted in Figure 1. Sequencing of these products detected a single missense mutation A1309G (V437I) in one FRCA isolate. Most of the FRCA isolates had an average of 4 silent mutations (observed in 6 isolates) and a single isolate had 6 silent mutations. A total of 8 different silent mutations were observed among FRCA isolates T1296C (83.3%), C1203T (66.7%), A1440G (66.7%), C1302T (50%), T1470C (50%), T1140C (25%), T1110C (16.7%), and T1284C (8.3%). Conclusion C. auris was the most common fluconazole resistant isolate observed, followed by C. glabrata, C. krusei, C. parapsilosis, C. albicans, C. tropicalis, and C. guilliermondii. There were many silent mutations observed in erg11 gene of FRCA isolates and detected only a single missense mutation (V437I). Fluconazole-resistant in FRCA isolates may be due to mechanisms other than the studied one in our region.
| S-EPMC9515968 | biostudies-literature
Project description:Cohort studies collect, generate and distribute data over long periods of time – often over the lifecourse of their participants. It is common for these studies to host a list of publications (which can number many thousands) on their website to demonstrate the impact of the study and facilitate the search of existing research to which the study data has contributed. The ability to search and explore these publication lists varies greatly between studies. We believe a lack of rich search and exploration functionality of study publications is a barrier to entry for new or prospective users of a study’s data, since it may be difficult to find and evaluate previous work in a given area. These lists of publications are also typically manually curated, resulting in a lack of rich metadata to analyse, making bibliometric analysis difficult. We present here a software pipeline that aggregates metadata from a variety of third-party providers to power a web based search and exploration tool for lists of publications. Alongside core publication metadata (i.e. author lists, keywords etc.), we include geocoding of first authors and citation counts in our pipeline. This allows a characterisation of a study as a whole based on common locations of authors, frequency of keywords, citation profile etc. This enriched publications metadata can be useful for generating study impact metrics and web-based graphics for public dissemination. In addition, the pipeline produces a research data set for bibliometric analysis or social studies of science. We use a previously published list of publications from a cohort study as an exemplar input data set to show the output and utility of the pipeline here.
| S-EPMC8108552 | biostudies-literature
Project description:Mounting evidence indicates that worldwide, innovation systems are increasing unsustainable. Equally, concerns about inequities in the science and innovation process, and in access to its benefits, continue. Against a backdrop of growing health, economic and scientific challenges global stakeholders are urgently seeking to spur innovation and maximize the just distribution of benefits for all. Open Science collaboration (OS) - comprising a variety of approaches to increase open, public, and rapid mobilization of scientific knowledge - is seen to be one of the most promising ways forward. Yet, many decision-makers hesitate to construct policy to support the adoption and implementation of OS without access to substantive, clear and reliable evidence. In October 2017, international thought-leaders gathered at an Open Science Leadership Forum in the Washington DC offices of the Bill and Melinda Gates Foundation to share their views on what successful Open Science looks like. Delegates from developed and developing nations, national governments, science agencies and funding bodies, philanthropy, researchers, patient organizations and the biotechnology, pharma and artificial intelligence (AI) industries discussed the outcomes that would rally them to invest in OS, as well as wider issues of policy and implementation. This first of two reports, summarizes delegates' views on what they believe OS will deliver in terms of research, innovation and social impact in the life sciences. Through open and collaborative process over the next months, we will translate these success outcomes into a toolkit of quantitative and qualitative indicators to assess when, where and how open science collaborations best advance research, innovation and social benefit. Ultimately, this work aims to develop and openly share tools to allow stakeholders to evaluate and re-invent their innovation ecosystems, to maximize value for the global public and patients, and address long-standing questions about the mechanics of innovation.
| S-EPMC7839829 | biostudies-literature
Project description: Not available
| S-EPMC10573385 | biostudies-literature
Project description:Background: Malaria continues to present a global health threat; the World Health Organization (WHO) reported 214 million cases of malaria by the year 2015 with a death rate of 438000. Sudan is endemic to malaria with over 95% of malaria cases due to Plasmodium falciparum. Chloroquine is a well-established drug in the treatment of P. falciparum malaria although its use has declined since its introduction as the drug of choice in treatment of malaria in Sudan. The mechanism of resistance has been attributed to mutations in P. falciparum Chloroquine resistance transporter gene coding for a key food vacuole proteins. In current study we aimed at verifying the genetic cause of resistance to Chloroquine in field isolates of P. falciparum. Methods: Twenty P. falciparum cases were diagnosed from East Nile hospital in Khartoum and recruited in the investigation. Nested PCR was conducted to isolate mutation region in the PfCRT gene and the amplicons were sequenced using Sanger sequencing technique (Macrogen, Soule Korea). Results: 16/20 (80%) of the field isolates contained base pair mutation of codon 76 in the pfcrt gene thus being resistant to chloroquine treatment and only 4/20 (20%) did not contain such mutation. Conclusions: High treatment failures associated with Chloroquine treatment is evident of the high prevalence of mutant strains of P. falciparum field isolates thus suggesting the reduced relevance of Chloroquine as a treatment choice in the management of P. falciparum malaria.
| S-EPMC5958312 | biostudies-literature
Project description:We recently observed the emergence of fluconazole-resistant Candida parapsilosis bloodstream isolates harboring a Y132F substitution in Erg11p in South Korea. These Y132F isolates had a higher propensity to cause clonal transmission than other fluconazole-resistant isolates and persisted within hospitals for several years, as revealed by microsatellite typing.
| S-EPMC6106402 | biostudies-literature
Project description:Background and purposeCandidiasis is referred to a group of superficial and deep-tissue fungal infections often caused by Candida albicans. The superficial infections affect the oral, oropharynx, esophagus, and vaginal mucosa. The treatment of choice for these infections is the use of azoles, such as fluconazole. However, the increased use of these antifungal agents has led to the emergence of azole-resistant isolates of C. albicans. Different mechanisms have been suggested for the development of drug resistance, such as mutations in the encoding gene ERG11. Mutations in ERG11 result in changes in the ERG11p spatial construction and reduce the affinity between the protein and azole. This study aimed to determine the susceptibility profile of C. albicans clinical isolates to fluconazole using microdilution method. The present research was also targeted toward the detection of mutations that might be related to fluconazole resistance by the amplification and sequencing of ERG11 gene.Materials and methodsThis study was conducted on a total of 216 clinical isolates obtained from Mashhad, Isfahan, and Tehran cities in Iran, during 2016-2018. The clinical isolates were identified using molecular techniques. Furthermore, minimum inhibitory concentration (MICs) was determined according to the clinical and laboratory standards institute M27-A3 and M27-S4 documents. The concentration range for fluconazole was obtained as 0.063-64 μg/ml. In the resistant strains, ERG11 genes were amplified by specific primers. Subsequently, cycle sequencing reactions were performed on purified polymerase chain reaction (PCR) products in forward and reverse directions. Finally, the results were analyzed by MEGA (version 7) and Gene Runner software (version 6.5.30).ResultsOut of 216 strains, 100 (46.3%) species were identified as C. albicans. The MIC values for fluconazole had a range of 0.125-16 μg/ml with the MIC50 and MIC90 values of 0.5 and 1 μg/ml, respectively. Totally, 41 nucleotide changes were detected among 4 resistant isolates. In this regard, 4 out of 41 mutations in codons caused changes in ERG11p; however, these mutations did not lead to fluconazole resistance.ConclusionFluconazole resistance among clinical isolates is not merely due to the changes in ERG11p. This resistance may be also related to some other mechanisms, such as the prevention of the intracellular accumulation of the antifungal agent and alteration of the target enzyme to diminish drug binding.
| S-EPMC6488286 | biostudies-literature
Project description:Acinetobacter baumannii has emerged as an important pathogen leading to multiple nosocomial outbreaks. Here, we describe the genomic sequence of a multidrug-resistant Acinetobacter baumannii sequence type 164 (ST164) isolate from a hospital patient in Sudan. To our knowledge, this is the first reported draft genome of an A. baumannii strain isolated from Sudan.
| S-EPMC6687919 | biostudies-literature
Project description:Background: Bladder adenocarcinoma (AC) is a scarce histological variant and there are few studies on its proper management. No previous case reports present the management of a urachal tumor and the incidental finding of bladder adenocarcinoma. Clinical case: We present the case of a young woman with nonspecific symptoms, who presented with a prior history of dysuria, bladder tenesmus, suprapubic pain and urinary urgency for one year, which had been treated as recurrent urinary tract infection. A partial cystectomy plus extended lymphadenectomy was scheduled. We found a bladder tumor with characteristics of a urachal tumor and the pathological report indicated a primary bladder AC. The patient had a complete recovery at one year of follow-up. Conclusions: A patient can present with a tumor with urachal characteristics; however, the pathology report can show primary AC. The decision to perform partial cystectomy was an appropriate option for the location of this tumor, with optimal surgical results. Still, a long-term follow-up is necessary. More specific management guidelines are required for the treatment of AC.
| S-EPMC7416577 | biostudies-literature