scholarly journals Prevalence and mechanisms of azole resistance in clinical isolates of Aspergillus section Fumigati species in a Canadian tertiary care centre, 2000 to 2013

2019 ◽  
Vol 75 (4) ◽  
pp. 849-858
Author(s):  
Maxime Parent-Michaud ◽  
Philippe J Dufresne ◽  
Eric Fournier ◽  
Benjamin Folch ◽  
Christine Martineau ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Tertiary Care ◽  
Geographic Area ◽  
Resistance Mechanisms ◽  
Sensu Stricto ◽  
Azole Resistance ◽  
Intrinsic Resistance ◽  
Tertiary Care Centre ◽  
Combined Use ◽  
Aspergillus Section

Abstract Objectives Azole resistance among Aspergillus fumigatus isolates is a growing concern worldwide. Induction of mutations during azole therapy, environment-acquired mutations caused by azole fungicides and intrinsic resistance of cryptic Fumigati species all contribute to the burden of resistance. However, there is a lack of data in Canada on this emerging threat. Methods To gain insights into the magnitude and mechanisms of resistance, a 14 year collection of Aspergillus section Fumigati comprising 999 isolates from 807 patients at a Montreal hospital was screened for azole resistance, and resistance mechanisms were investigated with the combined use of genome sequencing, 3D modelling and phenotypic efflux pump assays. Results Overall azole resistance was low (4/807 patients; 0.5%). A single azole-resistant A. fumigatus sensu stricto strain, isolated from a patient with pulmonary aspergillosis, displayed efflux-pump-mediated resistance. Three patients were colonized or infected with azole-resistant cryptic Fumigati species (one Aspergillus thermomutatus, one Aspergillus lentulus and one Aspergillus turcosus). Evidence is presented that azole resistance is efflux-pump-mediated in the A. turcosus isolate, but not in the A. lentulus and A. thermomutatus isolates. Conclusions Azole resistance is rare in our geographic area and currently driven by cryptic Fumigati species. Continued surveillance of emergence of resistance is warranted.

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 48-49
Author(s):  
Javaid Ahmad Bhat ◽  
Shariq Rashid Masoodi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Tertiary Care ◽  
Resistance Mechanisms ◽  
North India ◽  
Global Public Health ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Effective Prevention ◽  
Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

scholarly journals Novel ERG11 and TAC1b Mutations Associated with Azole Resistance in Candida auris

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Jizhou Li ◽  
Alix T. Coste ◽  
Maroussia Liechti ◽  
Daniel Bachmann ◽  
Dominique Sanglard ◽  
...  
Keyword(s):  
Invasive Candidiasis ◽  
Efflux Pump ◽  
Cumulative Effect ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Candida Auris ◽  
Content Type ◽  
Drug Classes ◽  
In The Wild

ABSTRACT Candida auris is a novel Candida species that has spread in all continents, causing nosocomial outbreaks of invasive candidiasis. C. auris has the ability to develop resistance to all antifungal drug classes. Notably, many C. auris isolates are resistant to the azole drug fluconazole, a standard therapy for invasive candidiasis. Azole resistance in C. auris can result from mutations in the azole target gene ERG11 and/or overexpression of the efflux pump Cdr1. TAC1 is a transcription factor controlling CDR1 expression in C. albicans. The role of TAC1 homologs in C. auris (TAC1a and TAC1b) remains to be better defined. In this study, we compared sequences of ERG11, TAC1a, and TAC1b between a fluconazole-susceptible and five fluconazole-resistant C. auris isolates of clade IV. Among four of the resistant isolates, we identified similar genotypes with concomitant mutations in ERG11 (F444L) and TAC1b (S611P). The simultaneous deletion of tandemly arranged TAC1a/TAC1b resulted in a decrease of MIC for fluconazole. Introduction of the ERG11 and TAC1b mutations separately and/or combined in the wild-type azole-susceptible isolate resulted in a significant increase of azole resistance with a cumulative effect of the two combined mutations. Interestingly, CDR1 expression was not significantly affected by TAC1a/TAC1b deletion or by the presence of the TAC1b S611P mutation, suggesting the existence of Tac1-dependent and Cdr1-independent azole resistance mechanisms. In conclusion, we demonstrated the role of two previously unreported mutations responsible for azole resistance in C. auris, which were a common signature among four azole-resistant isolates of clade IV.

scholarly journals Unveiling azole resistance mechanisms in Candida glabrata clinical isolates encoding wild-type or gain-of-function CgPdr1 alleles

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Sara B. Salazar ◽  
Noémi Valez ◽  
Danielle Sotti-Novais ◽  
Rita Simões ◽  
José António Souza ◽  
...  
Keyword(s):  
Large Scale ◽  
Target Genes ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Azole Resistance ◽  
Gain Of Function ◽  
Resistance Phenotype ◽  
Rapid Acquisition ◽  
The One

The relevance of C. glabrata as a human pathogen is linked with its poor susceptibility to azoles as well as its extreme genomic plasticity that allows the rapid acquisition of resistance. Extensive characterization of azole-resistant C. glabrata strains unveiled the central role of the transcriptional regulator CgPdr1 in the resistance phenotype, with many strains encoding hyperactive (or gain-of-function; GOF) CgPdr1 alleles. Large scale profiling of a collection of clinical C. glabrata isolates recovered in hospitals of the Lisbon area, in Portugal, led to the identification of 11 strains exhibiting resistance to fluconazole and voriconazole, while 2 were only resistant to fluconazole. Among these strains, 10 were found to encode alleles of the CgPDR1 gene harbouring multiple non-synonymous SNPs that were not found in the alleles encoded by susceptible strains, including K274Q, I392M and I803T not previously described as GOF mutations. The isolates encoding these alleles were found to over-express several CgPdr1 target genes including the azole efflux pump CgCDR1 sustaining the idea that these represent new gain-of-function CgPdr1 alleles. Only one of the identified azole-resistant strains was found to encode a CgPDR1 allele fully identical to the one encoded by susceptible strains. To better understand the resistance phenotype of this strain, its transcriptome was compared with the one of a susceptible strain and of strains encoding CgPdr1 GOF alleles. The results of this comparative transcriptomic analysis will be discussed shedding light into the different azole-resistance mechanisms evolved by C. glabrata, including those independent of CgPdr1 GOF strains.

EVALUATION OF THE ROLE OF D- DIMER TEST IN THE PREDICTION AND EXCLUSION OF VENOUS THROMBOEMBOLISM IN COMBINATION WITH PRETEST PROBABILITY SCORE AT A TERTIARY CARE CENTRE.

2021 ◽  
pp. 70-71
Author(s):  
Veerendra Tyagi ◽  
K.K Magnani ◽  
Jyoti P Shrivastava ◽  
Arun Jain ◽  
K.S. Mangal
Keyword(s):  
Venous Thromboembolism ◽  
Tertiary Care ◽  
Pretest Probability ◽  
Radiological Imaging ◽  
Imaging Studies ◽  
Tertiary Care Centre ◽  
Probability Score ◽  
Combined Use ◽  
D Dimer

Background: Clinical suspicion of venous thromboembolism requires objective testing to predict and exclude the diagnosis. Plasma D-dimer is sensitive marker for thrombosis but lack specicity. The combined use of pretest probability score and D-dimer can be used for exclusion of VTE and safely avoid costly imaging tests. Material and Methods: In this prospective observational study, we used Wells PTP score and D-dimer test to evaluate 50 patients who presented with sign and symptoms of VTE. Radiological imaging studies were taken as conrmatory test. Result: The sensitivity, specicity and NPV of D-dimer test were 100%, 83.7% and 100% respectively. The sensitivity, specicity and NPV of Ddimer test in combination with low PTP score were 100%, 72.1% and 100% respectively. The agreement between radiologically conrmed cases and D-dimer test was signicant. Conclusion: D-dimer test can be safely used in low or moderate PTP score patients to exclude VTE and costly invasive radiological imaging studies can be obviated in a signicant proportion of patients.

scholarly journals A Comparative Transcriptome Between Anti-drug Sensitive and Resistant Candida auris in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenkai Zhou ◽  
Xiuzhen Li ◽  
Yiqing Lin ◽  
Wei Yan ◽  
Shuling Jiang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Efflux Pump ◽  
Growth Conditions ◽  
Resistance Mechanisms ◽  
Transcriptomic Analysis ◽  
Intrinsic Resistance ◽  
First Line ◽  
Candida Auris ◽  
Future Studies ◽  
Resistance Rates

Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.

Mutations in nalc gene of Mex AB-OprM efflux pump in carbapenem resistant Pseudomonas aeruginosa isolated from burn wounds in Yazd, Iran

2020 ◽  
Author(s):  
Fatemeh Akhavan Tafti ◽  
Gilda Eslami ◽  
Hengameh Zandi ◽  
Kazem Barzegar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Resistant Isolate ◽  
Wound Infections ◽  
Intrinsic Resistance ◽  
Burn Wound ◽  
Cross Sectional ◽  
Burn Wounds ◽  
Carbapenem Resistant

Background and Objectives: Burn wound infections have emerged as an important cause of morbidity and mortality in patients due to prolonged hospital stay.  Pseudomonas aeruginosa, is the second cause of bacterial burn wound infections. Resistance mechanisms among P. aeruginosa are intrinsic or acquired. Intrinsic resistance mechanisms among P. aeruginosa isolates are inducible AmpC cephalosporinase, decrease of specific porin OprD, and overexpression of RND efflux pump. The aim of this study was detection of mutations in nalC gene in carbapenem resistant P. aeruginosa isolated from burn wounds. Materials and Methods: In this cross-sectional study, 180 burn-wound specimens were collected. Suspected lactose-nega- tive colonies were identified by conventional biochemical methods. Kirby-Bauer and Etest methods were used for suscepti- bility testing. PCR and sequencing techniques were used for the detection of nalC mutation. Results: Out of 180 specimens received in the laboratory, 54 of isolates were isolated and identified as P. aeroginosa (30%). Of these isolates 20 (37%) were resistant to at least two carbapenems simultaneously. From these carbapenem resistant iso- lates, 19 (95%), 14 (70%), 14 (70%), 19 (95%) and 16 (80%) were resistant to imipenem, cefepime, piperacillin, ceftizoxime and gentamicin, respectively. Only 1 (2%) isolate was sensitive to all carbapenems and did not has mutation in nalC gene, 20 (37%) isolates were resistant to at least two carbapenems, and had mutations in nalC gene (Gly71►Glu and Ser209►Arg). Conclusion: As the results showed, mutation in efflux pump was observed in carbapenem resistant isolate and this confirmed that the indiscriminate use of antibiotics for treatment or prophylaxis can increase mutation in efflux pump.

scholarly journals Intrinsic Resistance ofBurkholderia cepaciaComplex to Benzalkonium Chloride

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Youngbeom Ahn ◽  
Jeong Myeong Kim ◽  
Ohgew Kweon ◽  
Seong-Jae Kim ◽  
Richard C. Jones ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Efflux Pump ◽  
The United States ◽  
Resistance Mechanisms ◽  
Pharmaceutical Products ◽  
Intrinsic Resistance ◽  
Efflux Pump Inhibitor ◽  
Proteomic Data ◽  
Vulnerable Patients ◽  
Carbonyl Cyanide

ABSTRACTPharmaceutical products that are contaminated withBurkholderia cepaciacomplex (BCC) bacteria may pose serious consequences to vulnerable patients. Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively used in medical applications and have been implicated in the coselection of antimicrobial resistance. The ability of BCC to degrade BZK, tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl), dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl, inhibition of the growth of 20 BCC strains was observed in disinfectant solutions that ranged from 64 to 256 µg/ml. The efflux pump inhibitor carbonyl cyanidem-chlorophenylhydrazone increased the sensitivity of bacteria to 64 µg/ml BZK. The 20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of benzyldimethylamine and benzylmethylamine as the initial metabolites suggested that the cleavage of the C alkyl-N bond occurred as the first step of BZK degradation by BCC bacteria. Proteomic data confirmed the observed efflux activity and metabolic inactivation via biodegradation in terms of BZK resistance of BCC bacteria, which suggests that the two main resistance mechanisms are intrinsic and widespread.IMPORTANCEBenzyldimethylalkylammonium chloride is commonly used as an antiseptic in the United States. Several recent microbial outbreaks were linked to antiseptics that were found to contain strains of theBurkholderia cepaciacomplex.Burkholderiaspecies survived in antiseptics, possibly because of the degradation of antiseptic molecules or regulation of relevant gene expression. In this study, we assessed the efflux pump and the potential ofB. cepaciacomplex bacteria to degrade benzyldimethylalkylammonium chloride and improved our understanding of the resistance mechanisms, by using proteomic and metabolic information. To our knowledge, this is the first systematic report of the intrinsic mechanisms ofB. cepaciacomplex strain resistance to benzyldimethylalkylammonium chloride, based on the metabolic and proteomic evidence for efflux pumps and the complete biodegradation of benzyldimethylalkylammonium chloride.

Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico

2019 ◽  
Vol 74 (7) ◽  
pp. 2047-2050 ◽  
Author(s):  
Maria F Gonzalez-Lara ◽  
Carla M Roman-Montes ◽  
Paulette Diaz-Lomeli ◽  
Andrea Rangel-Cordero ◽  
Maria O Valenzuela ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Screening Test ◽  
Mutation Screening ◽  
Tertiary Care ◽  
Dna Amplification ◽  
Clinical Samples ◽  
Pcr Analysis ◽  
Azole Resistance ◽  
Tertiary Care Centre

AbstractBackgroundFungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates.ObjectivesWe screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus.MethodsAspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records.ResultsWe screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy.ConclusionsTo the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.

scholarly journals Efflux mediated chlorpyrifos tolerance in Escherichia coli BL21(DE3)

2020 ◽  
Author(s):  
Aswathi Aswathi ◽  
Ashok Pandey ◽  
Rajeev K Sukumaran
Keyword(s):  
Escherichia Coli ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Antibiotics Resistance ◽  
High Tolerance ◽  
Intrinsic Resistance ◽  
Efflux Pump Inhibitor ◽  
Environmental Strain

AbstractBacteria are continually challenged with variety of synthetic chemicals/xenobiotics in their immediate surroundings, including pesticides. Chlorpyrifos is one of the most commonly used organophosphate pesticides in the world. The non-environmental strain of Escherichia coli, BL21 (DE3) displayed high tolerance to chlorpyrifos but with no/negligible degradation. The intrinsic resistance mechanisms that aid the organism in its high tolerance are probed. Efflux pumps being ubiquitous in nature and capable of conferring resistance against wide variety of xenobiotics were found to be over-expressed in the presence of CP. Also, an efflux pump inhibitor PAβN increased the susceptibility of E. coli to chlorpyrifos due to the intracellular accumulation of CP. The tripartite efflux pump EmrAB-TolC with increased expression in both transcript and protein on CP exposure, might play a major role in CP tolerance. The transcriptional regulators involved in multidrug resistance along with transporters belonging to all the major families conferring antimicrobial resistance were up-regulated. Also up-regulated were the genes involved in phopshonate metabolism and all the genes in the copper or silver export system. The common resistance mechanisms i.e, activation of efflux pumps between CP, antibacterial metals and antibiotics resistance might result in cross-resistance, ultimately increasing the prevalence of multidrug resistant strains, making infections hard to treat.

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