scholarly journals Role of embB in natural and acquired resistance to ethambutol in mycobacteria.

1997 ◽  
Vol 41 (10) ◽  
pp. 2270-2273 ◽  
Author(s):  
F Alcaide ◽  
G E Pfyffer ◽  
A Telenti
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Practical Implication ◽  
Acquired Resistance ◽  
Fold Increase ◽  
Drug Susceptibility ◽  
Natural Resistance ◽  
Intrinsic Resistance ◽  
Resistant Strains ◽  
High Level

The mycobacterial embCAB operon encodes arabinosyl transferases, putative targets of the antimycobacterial agent ethambutol (EMB). Mutations in embB lead to resistance to EMB in Mycobacterium tuberculosis. The basis for natural, intrinsic resistance to EMB in nontuberculous mycobacteria (NTM) is not known; neither is the practical implication of resistance to EMB in the absence of embB mutations in M. tuberculosis well understood. The conserved embB resistance-determining region (ERDR) of a collection of 13 strains of NTM and 12 EMB-resistant strains of M. tuberculosis was investigated. Genotypes were correlated with drug susceptibility phenotypes. High-level natural resistance to EMB (MIC, . or =64 microg/ml) was associated with a variant amino acid motif in the ERDR of M. abscessus, M. chelonae, and M. leprae. Transfer of the M. abscessus emb allele to M. smegmatis resulted in a 500-fold increase in the MICs. In M. tuberculosis, embB mutations were associated with MICs of > or =20 microg/ml while resistance not associated with an ERDR mutation generally resulted in MICs of < or =10 microg/ml. These data further support the notion that the emb region determines intrinsic and acquired resistance to EMB and might help in the reassessment of the current recommendations for the screening and treatment of infections with EMB-resistant M. tuberculosis and NTM.

scholarly journals Development of fluoroquinolone resistance in Enterococcus faecalis and role of mutations in the DNA gyrase gyrA gene.

1996 ◽  
Vol 40 (11) ◽  
pp. 2558-2561 ◽  
Author(s):  
J Tankovic ◽  
F Mahjoubi ◽  
P Courvalin ◽  
J Duval ◽  
R Leclerco
Keyword(s):  
Enterococcus Faecalis ◽  
Resistant Isolate ◽  
Fluoroquinolone Resistance ◽  
Gyra Gene ◽  
Single Clone ◽  
Total Dna ◽  
Resistant Strains ◽  
French Hospital ◽  
High Level

We have analyzed the development of fluoroquinolone resistance between 1986 and 1993 among clinical isolates of Enterococcus faecalis from a French hospital. One hundred randomly selected isolates per year were screened for resistance to ciprofloxacin (MIC > 2 micrograms/ml) and for high-level resistance to gentamicin (MIC > 1,000 micrograms/ml). The percentages of ciprofloxacin-resistant strains for these years were as follows: 1986, 0; 1987, 1; 1988 to 1989, 2; 1990, 6; 1991, 16; 1992, 24; and 1993, 14. Eighty-three percent of the ciprofloxacin-resistant isolates were coresistant to high levels of gentamicin. Forty-eight high-level gentamicin-resistant E. faecalis strains, which were resistant (24 strains) or susceptible (24 strains) to ciprofloxacin, were examined by pulsed-field gel electrophoresis (PFGE) of SmaI-digested total DNA. Numerous PFGE types were observed among the ciprofloxacin-susceptible isolates, whereas one type was largely predominant among the ciprofloxacin-resistant strains, which suggests that the increase in fluoroquinolone resistance was due to the spread of a single clone. A 241-bp fragment of gyrA, corresponding to the quinolone resistance-determining region, was amplified and sequenced for seven ciprofloxacin-resistant isolates. Six strains had high levels of resistance (MICs, 32 to 64 micrograms/ml) and had a mutation at position 83 (Escherichia coli coordinates) from Ser to Arg (three strains) or to Ile (two strains) or at position 87 from Glu to Gly (one strain), whereas the low-level-resistant isolate (MIC, 8 micrograms/ml) had no mutations.

scholarly journals Antimicrobial Resistance of Listeria monocytogenes Strains Isolated from Humans in France

2010 ◽  
Vol 54 (6) ◽  
pp. 2728-2731 ◽  
Author(s):  
A. Morvan ◽  
C. Moubareck ◽  
A. Leclercq ◽  
M. Hervé-Bazin ◽  
S. Bremont ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Antimicrobial Resistance ◽  
Resistant Strain ◽  
Temporal Evolution ◽  
Acquired Resistance ◽  
Mechanisms Of Resistance ◽  
Resistant Strains ◽  
High Level ◽  
Level Resistance ◽  
Microbiological Surveillance

ABSTRACT Susceptibility to antibiotics of 4,816 clinical L. monocytogenes strains isolated since 1926 was studied, and the temporal evolution of susceptibility to antibiotics was analyzed through several decades. The mechanisms of resistance in each resistant strain were studied. The prevalence of resistant strains was estimated at 1.27% among isolates from humans. Resistance to tetracyclines+ and fluoroquinolones was more common and has recently emerged. Although acquired resistance in clinical L. monocytogenes did not implicate clinically relevant antibiotics, the possibility of resistance gene transfers, the description of the first clinical isolate with high-level resistance to trimethoprim, and the recent increase in penicillin MICs up to 2 μg/ml reinforce the need for microbiological surveillance.

scholarly journals Role of Hypermutability in the Evolution of the Genus Oenococcus

2007 ◽  
Vol 190 (2) ◽  
pp. 564-570 ◽  
Author(s):  
Angela M. Marcobal ◽  
David A. Sela ◽  
Yuri I. Wolf ◽  
Kira S. Makarova ◽  
David A. Mills
Keyword(s):  
Lactic Acid ◽  
Leuconostoc Mesenteroides ◽  
Genomic Analysis ◽  
Oenococcus Oeni ◽  
Mutation Rates ◽  
Comparative Genomic ◽  
Allelic Polymorphism ◽  
Resistant Strains ◽  
High Level

ABSTRACT Oenococcus oeni is an alcohol-tolerant, acidophilic lactic acid bacterium primarily responsible for malolactic fermentation in wine. A recent comparative genomic analysis of O. oeni PSU-1 with other sequenced lactic acid bacteria indicates that PSU-1 lacks the mismatch repair (MMR) genes mutS and mutL. Consistent with the lack of MMR, mutation rates for O. oeni PSU-1 and a second oenococcal species, O. kitaharae, were higher than those observed for neighboring taxa, Pediococcus pentosaceus and Leuconostoc mesenteroides. Sequence analysis of the rpoB mutations in rifampin-resistant strains from both oenococcal species revealed a high percentage of transition mutations, a result indicative of the lack of MMR. An analysis of common alleles in the two sequenced O. oeni strains, PSU-1 and BAA-1163, also revealed a significantly higher level of transition substitutions than were observed in other Lactobacillales species. These results suggest that the genus Oenococcus is hypermutable due to the loss of mutS and mutL, which occurred with the divergence away from the neighboring Leuconostoc branch. The hypermutable status of the genus Oenococcus explains the observed high level of allelic polymorphism among known O. oeni isolates and likely contributed to the unique adaptation of this genus to acidic and alcoholic environments.

The role of hydrogen gas bubble in hydrophobic properties in mixed micro layer (Al2O3+Mg)

2020 ◽  
Vol 1 (105) ◽  
pp. 5-16
Author(s):  
R. Subagyo ◽  
I.N.G. Wardana ◽  
A. Widodo ◽  
E. Siswanto
Keyword(s):  
Surface Tension ◽  
Practical Implication ◽  
Gas Bubbles ◽  
Droplet Surface ◽  
Hydrogen Gas ◽  
Hydrophobic Properties ◽  
Micro Particles ◽  
Hydrophobic Nature ◽  
High Level

Purpose: To find out more about the role of hydrogen gas bubbles in improving the hydrophobic nature of a layer, especially in the layers of microparticles Alumina (Al2O3) with Magnesium (Mg). Design/methodology/approach: The method used is an experimental method by first conducting the SEM-Edx test, testing the content of the elements in the waxy layer and observing the topographic shape on the surface of the taro leaves. Then prepare a mixture of Alumina micro particles with Magnesium to investigate the hydrophobicity of the taro leaves. The mixed presentations between Alumina and Magnesium are: (0, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100%). Findings: The results of this study found three conditions of the Alumina and Magnesium mix layer when in contact with a droplet, namely: Hydrophobic conditions occur when the surface structure of the rough mixed micro layer forms micro crevices, then bubbles of hydrogen gas fill it to form trapped gases. When droplets come in contact with the surface of the mixed layer the effect of the gas being trapped is very effective at creating hydrophobic properties. While the transition conditions occur when more and more hydrogen gas bubbles along with the increasing percentage of Mg and the opposite occurs in micro particle fissures. Bubbles fill the micro-gap space fully so that the tops of the micro particles are covered by bubbles. This causes the droplet surface tension to weaken, so the droplet contact angle decreases. Furthermore, hydrophilic conditions occur when the micro gap is getting narrower as the percentage of Mg increases and the formation of hydrogen gas bubbles increases. The high level of bubble density in the micro gap closes the peaks of the micro particles, which results in the surface tension of the droplet getting weaker. In this weak surface tension condition, the hydrogen bubble can break through the droplet surface tension and change its hydrophobic nature to hydrophilic. Research limitations/implications: This research is limited to the hydrophobicity of Alumina and Magnesium materials, mainly to investigate the role of hydrogen gas in supporting the hydrophobic nature of taro leaves (Colocasia esculenta). Practical implications: The practical implication in this study is the use of hydrophobic membranes which are widely applied to filtration. Originality/value: Discovered the composition of a membrane mixture of Alumina (Al2O3) and Magnesium (Mg) to create hydrophilic and hydrophobic conditions.

scholarly journals PROGNOSIS OF NEOADJUVANT CHEMOTHERAPY EFFICACY WITH IMMUNOBIOLOGIC TUMOR MARKERS IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

2019 ◽  
pp. 46-54
Author(s):  
S. A. Lyalkin ◽  
N. O. Verevkina ◽  
L. A. Syvak
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Fold Increase ◽  
Predictive Role ◽  
High Level ◽  
Chemotherapy Efficacy ◽  
Cd4 Lymphocytes

Treatment of patients with triple negative breast cancer (TNBC) remains one of the most difficult problems in clinical oncology. Despite the negative prognosis for TNBC, there exists the group of patients with better response to the therapy and better prognosis, which proves the heterogenity of TNBC. The aim of the study was to evaluate the predictive role of tumor infiltrative lymphocytes (TIL) and their subpopulations (CD4+, CD8+ and FOXP3) in patients with TNBC. The predictive role of clinical, morphologic and immunohystochemical tumor features on neoadjuvant chemotherapy (NACT) efficacy was assessed in 52 TNBC patients. The risk of incomplete pathomorphologic response after NACT is related with 2 biomarkers: level of TIL and stromal CD4+ lymphocytes. The increase of TIL level decreases of the risk of incomplete pathomorphologic response (P = 0.01), ОR = 0.07 (95 % CІ 0.01–0.55) while standartization on CD4+ level. The high level of TIL at the time of diagnosis significantly decreases the risk of incomplete pathomorphologic response (OR = 0,2; P = 0,02). The group of patients with the ratio of stromal lymphocytes CD4low/CD8low had the eight-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD4high/CD8high (ОR = 8,0; Р = 0,03); the patient with the ratio stromal lymphocytes CD8low/ FOXP3low had the almost two-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD8high/FOXP3high (ОR = 2,1; Р = 0,03).

scholarly journals Multidrug Resistance of a Porin Deletion Mutant of Mycobacterium smegmatis

2004 ◽  
Vol 48 (11) ◽  
pp. 4163-4170 ◽  
Author(s):  
Joachim Stephan ◽  
Claudia Mailaender ◽  
Gilles Etienne ◽  
Mamadou Daffé ◽  
Michael Niederweis
Keyword(s):  
Multidrug Resistance ◽  
Outer Membrane ◽  
Mycobacterium Smegmatis ◽  
Antibiotic Sensitivity ◽  
Chemotherapeutic Agents ◽  
Intrinsic Resistance ◽  
Successful Design ◽  
High Level ◽  
Outer Membrane Permeability

ABSTRACT Mycobacteria contain an outer membrane of unusually low permeability which contributes to their intrinsic resistance to many agents. It is assumed that small and hydrophilic antibiotics cross the outer membrane via porins, whereas hydrophobic antibiotics may diffuse through the membrane directly. A mutant of Mycobacterium smegmatis lacking the major porin MspA was used to examine the role of the porin pathway in antibiotic sensitivity. Deletion of the mspA gene caused high-level resistance of M. smegmatis to 256 μg of ampicillin/ml by increasing the MIC 16-fold. The permeation of cephaloridine in the mspA mutant was reduced ninefold, and the resistance increased eightfold. This established a clear relationship between the activity and the outer membrane permeation of cephaloridine. Surprisingly, the MICs of the large and/or hydrophobic antibiotics vancomycin, erythromycin, and rifampin for the mspA mutant were increased 2- to 10-fold. This is in contrast to those for Escherichia coli, whose sensitivity to these agents was not affected by deletion of porin genes. Uptake of the very hydrophobic steroid chenodeoxycholate by the mspA mutant was retarded threefold, which supports the hypothesis that loss of MspA indirectly reduces the permeability by the lipid pathway. The multidrug resistance of the mspA mutant highlights the prominent role of outer membrane permeability for the sensitivity of M. smegmatis to antibiotics. An understanding of the pathways across the outer membrane is essential to the successful design of chemotherapeutic agents with activities against mycobacteria.

scholarly journals New Fks Hot Spot for Acquired Echinocandin Resistance inSaccharomyces cerevisiaeand Its Contribution to Intrinsic Resistance ofScedosporiumSpecies

2011 ◽  
Vol 55 (8) ◽  
pp. 3774-3781 ◽  
Author(s):  
Michael E. Johnson ◽  
Santosh K. Katiyar ◽  
Thomas D. Edlind
Keyword(s):  
Hot Spot ◽  
Acquired Resistance ◽  
Direct Interaction ◽  
Site Directed Mutagenesis ◽  
Side Chain ◽  
Cell Wall Polysaccharide ◽  
Intrinsic Resistance ◽  
Scedosporium Prolificans ◽  
Echinocandin Resistance

ABSTRACTEchinocandins represent a new antifungal group with potent activity againstCandidaspecies. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two “hot spot” regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are usingSaccharomyces cerevisiaeto understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in anfks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation inCandida glabrataconfirmed the role of the new “hot spot 3” in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RESScedosporiumspecies revealed W695F-equivalent substitutions; Fks1 hybrids expressingScedosporium prolificanshot spot 3 confirmed that this substitution imparts RES.

scholarly journals Genetic diversity and antimicrobial resistance of enterococcal isolates from Southern region of Brazil

2006 ◽  
Vol 48 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Pedro Alves d'Azevedo ◽  
Cícero Armídio Gomes Dias ◽  
Lúcia Martins Teixeira
Keyword(s):  
Genetic Diversity ◽  
Antimicrobial Agents ◽  
Acquired Resistance ◽  
Chromosomal Dna ◽  
Pfge Analysis ◽  
Clonal Group ◽  
Group A ◽  
Resistant Strains ◽  
High Level ◽  
The City

In the present study, a total of 455 enterococcal isolates, recovered from patients living in the city of Porto Alegre, State of Rio Grande do Sul, Brazil, during the period from July 1996 to June 1997, were identified to the species level by conventional biochemical and microbiological tests, and assayed for their susceptibilities to antimicrobial agents. The genetic diversity of antimicrobial resistant strains was evaluated by pulsed-field gel electrophoresis (PFGE) analysis of SmaI restricted chromosomal DNA. The most frequent species was Enterococcus faecalis (92.8%). Other species identified were: E. faecium (2.9%), E. gallinarum (1.5%), E. avium (1.1%), E. hirae (0.7%), E. casseliflavus (0.4%), E. durans (0.4%) and E. raffinosus (0.2%). The overall prevalence of isolates with high-level resistance (HLR) to aminoglycosides was 37.8%. HLR to gentamicin was found in 24.8%. No strains with acquired resistance to vancomycin were found. PFGE analysis showed the predominance of clonal group A, comprising strains isolated from different clinical specimens obtained from patients in three hospitals. These results suggest intra and inter-hospital dissemination of one predominant clonal group of E. faecalis isolates with HLR to gentamicin in the hospitals included in this study.

scholarly journals Non-pncAGene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

2017 ◽  
Vol 55 (6) ◽  
pp. 1920-1927 ◽  
Author(s):  
Jim Werngren ◽  
Erik Alm ◽  
Mikael Mansjö
Keyword(s):  
Susceptibility Testing ◽  
Gene Mutations ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Techniques ◽  
Content Type ◽  
Resistant Strains ◽  
Clear Majority

ABSTRACTPyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB).pncAgene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDRPZA-STB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-typepncAgene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy:panDorrpsAmutations identified by whole-genome sequencing (WGS) (n= 7), heteroresistance (n= 8), and mixed populations withMycobacterium avium(n= 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-Rclinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymouspncAmutation (Thr87Met), whereas a nonsynonymousrpsAmutation was found in 17 isolates. None of these isolates carried a nonsynonymouspanDmutation, while all 15 of the MDRPZA-Risolates harbored a nonsynonymouspncAmutation. Our findings indicate that it is necessary to consider the occurrence ofpanDmutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymousrpsAmutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role ofrpsAin PZA resistance.

scholarly journals PROBLEMS OF THE TREATMENT OF PNEUMONIA CAUSED BY PSEUDOMONAS AERUGINOSA

2019 ◽  
Vol 42 (3) ◽  
pp. 78-83
Author(s):  
Mochonyi V. A. ◽  
Savchenko O. A. ◽  
Podsevakhina S. L. ◽  
Tkachenko O. V.
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Poor Prognosis ◽  
Acquired Resistance ◽  
Severe Pneumonia ◽  
Natural Resistance ◽  
Beta Lactams ◽  
Pseudomonas Infection ◽  
High Level

Pseudomonas infection is one of the most problematic pathogens of pneumonia, because it has natural resistance to many antibiotics, is able to quickly form acquired resistance, often causes severe pneumonia with a poor prognosis. Analysis of the literature data showed that today P. Aeruginosa demonstrates resistance to all anti-pest control antibiotics, with the exception of polymyxin. The levels of resistance of P.Aeruginosa are very considerably depending on the region of the survey and the profile of the hospital, which requires monitoring the sensitivity of microorganisms in each department of the hospital. The data on the degree of resistance to P. Aeruginosa antibiotics in Ukraine are limited, but available local studies on this issue also show a high level of resistance of this microorganism to the main anti-pest antibiotics. In patients with pneumonia and risk factors for the involvement of Pseudomonas infection, most authors recommend combination antibiotic therapy, which has a synergistic effect on P. Aeruginosa, which allows, in most cases, to overcome the resistance of this microorganism. According to the literature, such synergism has been proven for the combination: beta-lactams (ceftazidime, cefepime, antipseudomonas carbapenems) + aminoglycosides (amikacin) or fluoroquinolones (ciprofloxacin or levofloxacin). The use of these drugs in the maximum allowable dose allows a higher degree of probability to achieve the eradication of P. Aeruginosa in patients with pneumonia and to improve the prognosis for this disease. Keywords: pneumonia, Pseudomonas Aeruginosa, resistance, treatment.

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