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Distribution of Genes Encoding Resistance to Macrolides, Lincosamides, and Streptogramins among Staphylococci

Lina, Gerard; Quaglia, Alain; Reverdy, Marie-Elisabeth; Leclercq, Roland; Vandenesch, François; Etienne, Jerome
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/1999 Português
Relevância na Pesquisa
656.5746%
The relative frequency of 10 determinants of resistance to macrolides, lincosamides, and streptogramins was investigated by PCR in a series of 294 macrolide-, lincosamide-, and/or streptogramin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci isolated in 1995 from 32 French hospitals. Resistance was mainly due to the presence of ermA or ermC genes, which were detected in 259 strains (88%), in particular those resistant to methicillin (78% of the strains). Macrolide resistance due to msrA was more prevalent in coagulase-negative staphylococci (14.6%) than in S. aureus (2.1%). Genes related to linA/linA′ and conferring resistance to lincomycin were detected in one strain of S. aureus and seven strains of coagulase-negative staphylococci. Resistance to pristinamycin and quinupristin-dalfopristin was phenotypically detected in 10 strains of S. aureus and in three strains of coagulase-negative staphylococci; it was always associated with resistance to type A streptogramins encoded by vat or vatB genes and occurred in association with erm genes. The vga gene conferring decreased susceptibility to type A streptogramins was present alone in three strains of coagulase-negative staphylococci and in combination with erm genes in 10 strains of coagulase-negative staphylococci. A combination of vga-vgb-vat and ermA genes was found in a single strain of S. epidermidis.

Antibiotic Resistance in Campylobacter Strains Isolated from Animals, Foods, and Humans in Spain in 1997–1998

Sáenz, Yolanda; Zarazaga, Myriam; Lantero, Marta; Gastañares, M. José; Baquero, Fernando; Torres, Carmen
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2000 Português
Relevância na Pesquisa
656.5558%
Colonization by Campylobacter strains was investigated in human, broiler, and pig fecal samples from 1997- 1998, as well as in foods of animal origin, and antibiotic susceptibility testing was carried out for these strains. Campylobacter strains were isolated in the foods of animal origin (55 of 101 samples; 54.4%), intestinal samples from broilers (85 of 105; 81%), and pigs (40 of 45; 88.9%). A total of 641 Campylobacter strains were isolated from 8,636 human fecal samples of clinical origin (7.4%). Campylobacter jejuni was the most frequently isolated species from broilers (81%) and humans (84%), and Campylobacter coli was most frequently isolated from pigs (100%). An extremely high frequency of ciprofloxacin resistance was detected among Campylobacter strains, particularly those isolated from broilers and pigs (99%), with a slightly lower result for humans (72%); cross-resistance with nalidixic acid was almost always observed. A higher frequency of resistance to erythromycin (81.1%), ampicillin (65.7%), gentamicin (22.2%), and amikacin (21.6%) was detected in C. coli strains isolated from pigs compared to those isolated from humans (34.5, 29.3, 8.6, and 0%, respectively). A low frequency of erythromycin resistance was found in C. jejuni or C. coli isolated from broilers. A greater resistance to ampicillin and gentamicin (47.4 and 11.9%...

Effect of Drug Concentration on Emergence of Macrolide Resistance in Mycobacterium avium

Nash, Kevin A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2001 Português
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656.6933%
The emergence of antibiotic resistance in mycobacteria involves the selection of mutant variants within a susceptible bacterial population. However, it is unclear whether antimycobacterial drugs act just as selective agents or can influence the rate of appearance of resistant mutants. The present study was initiated to address this issue by monitoring the effects of antimicrobial agents on the appearance and growth of clarithromycin (CLR)-resistant (CLRr) bacilli in broth cultures of Mycobacterium avium. Preexposure of M. avium to CLR had a significant dose effect on the emergence of resistance, with concentrations of 4 to 8 μg/ml resulting in a maximal (∼104-fold) increase in the number of CLRr bacilli after a 4-day incubation. In addition, a dose effect was found with azithromycin. The use of combinations of CLR with either ethambutol (EMB) or rifabutin (RFB) resulted in fewer resistant bacilli compared to the use of CLR alone. The lowest active concentration of EMB (4 μg/ml) was equivalent to the EMB MIC (4 to 8 μg/ml) for the parental CLRs strain and the emergent CLRr variants, and thus, the antiresistance effect was probably the result of the bacteriostatic effect of EMB on CLRr bacilli. However, RFB was an order of magnitude more active (0.05 μg/ml) at reducing resistance than suggested by the MIC of this agent (0.5 to 1 μg/ml). These results indicate that the emergence of resistance was not simply the selection of a preexisting subpopulation of resistant bacilli. Further analysis suggested that early events in the emergence of resistance involved organisms (progenitors) that acquired a resistance phenotype. In addition...

Genetic Organization of the Chromosome Region Surrounding mecA in Clinical Staphylococcal Strains: Role of IS431-Mediated mecI Deletion in Expression of Resistance in mecA-Carrying, Low-Level Methicillin- Resistant Staphylococcus haemolyticus

Katayama, Yuki; Ito, Teruyo; Hiramatsu, Keiichi
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2001 Português
Relevância na Pesquisa
656.5746%
We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S. haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS431L was located to the left of an intact mecI gene, forming the structure IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L was associated with the deletion of mecI and mecR1, forming the structure IS431L-ΔmecR1-mecA-IS431mec, designated the class C mecA gene complex. Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS431L-class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC...

Aminoglycoside Resistance with Homogeneous and Heterogeneous Populations of Antibiotic-Resistant Ribosomes

Recht, Michael I.; Puglisi, Joseph D.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2001 Português
Relevância na Pesquisa
656.6626%
Aminoglycosides bind to rRNA in the small subunit of the bacterial ribosome. Mutations in the decoding region of 16S rRNA confer resistance to specific subsets of aminoglycoside antibiotics. The two major classes of 2-deoxystreptamine aminoglycosides are the 4,5- and the 4,6-disubstituted antibiotics. Antibiotics of the 4,5-disubstituted class include neomycin, paromomycin, and ribostamycin. Gentamicins and kanamycins belong to the 4,6-disubstituted class of aminoglycosides. Structural studies indicated the potential importance of position 1406 (Escherichia coli numbering) in the binding of ring III of the 4,6-disubstituted class of aminoglycosides to 16S rRNA. We have introduced a U1406-to-A mutation in a plasmid-encoded copy of E. coli 16S rRNA which has been expressed either in a mixture with wild-type ribosomes or in a strain in which all rRNA is transcribed from the plasmid-encoded rrn operon. High-level resistance to many of the 4,6-disubstituted aminoglycosides is observed only when all the rRNA contains the U1406-to-A mutation. In contrast to the partial dominance of resistance observed with other mutations in the decoding region, there is a dominance of sensitivity with the 1406A mutation. Chemical footprinting experiments indicate that resistance arises from a reduced affinity of the antibiotic for the rRNA target. These results demonstrate that although position 1406 is an important determinant in the binding and action of the 4...

Influence of the TonB Energy-Coupling Protein on Efflux-Mediated Multidrug Resistance in Pseudomonas aeruginosa

Zhao, Qixun; Li, Xian-Zhi; Mistry, Anita; Srikumar, Ramakrishnan; Zhang, Li; Lomovskaya, Olga; Poole, Keith
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/1998 Português
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656.6712%
TonB couples the energized state of the cytoplasmic membrane to the operation of outer membrane receptors responsible for Fe(III) siderophore uptake across the outer membrane of gram-negative bacteria. A tonB mutant of Pseudomonas aeruginosa deficient in iron siderophore uptake was shown in the present study to be hypersusceptible to a wide variety of antibiotics, reminiscent of the phenotype of mutants defective in the mexAB-oprM antibiotic efflux operon. This was not related to influences of a tonB mutation on the iron status of the cell, and indeed, intrinsic antibiotic susceptibility and mexAB-oprM expression were unaffected by iron levels in the growth medium. The presence of tonB on a multicopy plasmid increased the level of resistance of a MexAB-OprM+ strain but not that of a MexAB-OprM− strain to a variety of antimicrobial agents. mexAB-oprM expression was not, however, altered in a tonB deletion mutant, indicating that any influence of TonB on MexAB-OprM-mediated multidrug resistance was at the level of pump activity. Consistent with this, drug accumulation assays revealed that the tonB deletion mutant exhibited decreased levels of drug efflux. Still, the multidrug resistance of a nalB strain was not wholly abrogated by a tonB mutation...

Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations

Sander, Peter; Springer, Burkhard; Prammananan, Therdsak; Sturmfels, Antje; Kappler, Martin; Pletschette, Michel; Böttger, Erik C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2002 Português
Relevância na Pesquisa
656.8417%
To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the decline in the level of resistance.

Mutant TEM β-Lactamase Producing Resistance to Ceftazidime, Ampicillins, and β-Lactamase Inhibitors

Vakulenko, Sergei; Golemi, Dasantila
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2002 Português
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657.042%
A derivative of the TEM-1 β-lactamase producing clinically significant levels of resistance to ceftazidime and β-lactamase inhibitors in the presence of penicillins was generated following five rounds of DNA shuffling and selection. This complex mutant enzyme contained three amino acid substitutions including those of residues 104 and 276 that are known to produce extended-spectrum resistance and, correspondingly, resistance to β-lactamase inhibitors. Although the Glu104Lys substitution by itself produced low levels of ceftazidime resistance, additional amino acid replacements in the enzyme with the triple mutation resulted in further enhancement of resistance to ceftazidime. Kinetic studies of the purified β-lactamase enzyme with the triple mutation indicated enhancement of the catalytic efficiency for turnover (kcat/Km) of ceftazidime. The increases in the Ki values of both clavulanic acid and tazobactam for the enzyme with the triple mutation were consistent with the observed bacterial resistance to the reversibility of β-lactam resistance with these inhibitors.

Telithromycin and Quinupristin-Dalfopristin Resistance in Clinical Isolates of Streptococcus pyogenes: SMART Program 2001 Data

Hsueh, Po-Ren; Teng, Lee-Jene; Lee, Chun-Ming; Huang, Wen-Kuei; Wu, Tsu-Lan; Wan, Jen-Hsien; Yang, Dine; Shyr, Jainn-Ming; Chuang, Yin-Ching; Yan, Jing-Jou; Lu, Jang-Jih; Wu, Jiunn-Jong; Ko, Wen-Chien; Chang, Feng-Yee; Yang, Yi-Chueh; Lau, Yeu-Jun; Liu, Y
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2003 Português
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656.6431%
This study evaluated the current status of antimicrobial resistance in clinical isolates of Streptococcus pyogenes in Taiwan as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. In 2001, 419 different isolates of S. pyogenes, including 275 from respiratory secretions, 87 from wound pus, and 31 from blood, were collected from nine hospitals in different parts of Taiwan. MICs of 23 antimicrobial agents were determined at a central location by the agar dilution method. All of the isolates were susceptible to penicillin (MIC at which 90% of the isolates were inhibited [MIC90], ≤0.03 μg/ml), cefotaxime (MIC90, ≤0.03 μg/ml), cefepime (MIC90, 0.06 μg/ml), meropenem (MIC90, ≤0.03 μg/ml), moxifloxacin (MIC90, 0.25 μg/ml), vancomycin (MIC90, 0.5 μg/ml), and linezolid (MIC90, 1 μg/ml). Overall, 78% of isolates were not susceptible to erythromycin (54% were intermediate, and 24% were resistant), and 5% were not susceptible to clindamycin. Of the 101 erythromycin-resistant isolates, 80.2% exhibited the M phenotype (mefA gene positive), 18.9% exhibited the cMLS (constitutive resistance to macrolides-lincosamides-streptogramin B [MLS]) phenotype (ermB gene positive), and 1% exhibited the iMLS (inducible resistance to MLS) phenotype (ermB gene positive). Fluoroquinolones (sitafloxacin > moxifloxacin > ciprofloxacin = levofloxacin = gatifloxacin > gemifloxacin) demonstrated potent activity against nearly all of the isolates of S. pyogenes tested. Thirty-two isolates (8%) were not susceptible to quinupristin-dalfopristin. Seventeen percent of isolates had telithromycin MICs of ≥1 μg/ml...

Plasmid-Mediated 16S rRNA Methylase in Serratia marcescens Conferring High-Level Resistance to Aminoglycosides

Doi, Yohei; Yokoyama, Keiko; Yamane, Kunikazu; Wachino, Jun-ichi; Shibata, Naohiro; Yagi, Tetsuya; Shibayama, Keigo; Kato, Haru; Arakawa, Yoshichika
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2004 Português
Relevância na Pesquisa
656.8417%
Serratia marcescens S-95, which displayed an unusually high degree of resistance to aminoglycosides, including kanamycins and gentamicins, was isolated in 2002 from a patient in Japan. The resistance was mediated by a large plasmid which was nonconjugative but transferable to an Escherichia coli recipient by transformation. The gene responsible for the aminoglycoside resistance was cloned and sequenced. The deduced amino acid sequence of the resistance gene shared 82% identity with RmtA, which was recently identified as 16S rRNA methylase conferring high-level aminoglycoside resistance in Pseudomonas aeruginosa. Histidine-tagged recombinant protein showed methylation activity against E. coli 16S rRNA. The novel aminoglycoside resistance gene was therefore designated rmtB. The genetic environment of rmtB was further investigated. The sequence immediately upstream of rmtB contained the right end of transposon Tn3, including blaTEM, while an open reading frame possibly encoding a transposase was identified downstream of the gene. This is the first report describing 16S rRNA methylase production in S. marcescens. The aminoglycoside resistance mechanism mediated by production of 16S rRNA methylase and subsequent ribosomal protection used to be confined to aminoglycoside-producing actinomycetes. However...

Gene Expression and Evolution of Antifungal Drug Resistance▿ †

Anderson, James B.; Sirjusingh, Caroline; Syed, Nazia; Lafayette, Shantelle
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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656.60625%
Permanent changes in gene expression result from certain forms of antifungal resistance. In this study, we asked whether any changes in gene expression are required for the evolution of a drug-resistant phenotype in populations. We examined the changes in gene expression resulting from the evolution of resistance in experimental populations of the yeast Saccharomyces cerevisiae with two antifungal drugs, fluconazole (FLC) in a previous study and amphotericin B (AmB) in this study, in which five populations were subjected to increasing concentrations of AmB, from 0.25 to 128 μg/ml in twofold increments. Six genes, YGR035C, YOR1, ICT1, GRE2, PDR16, and YPLO88W, were consistently overexpressed with resistance to AmB reported here and with resistance to FLC involving a mechanism of increased efflux reported previously. We then asked if the deletion of these genes impaired the ability of populations to evolve resistance to FLC over 108 generations of asexual reproduction in 32 and 128 μg/ml FLC, the same conditions under which FLC-resistant types evolved originally. For each of three deletion strains, YOR1, ICT1, and PDR16 strains, extinctions occurred in one of two replicate populations growing in 128 μg/ml FLC. Each of these three deletion strains was mixed 1:1 with a marked version of the wild type to measure the relative ability of the deletion strain to adapt over 108 generations. In these assays...

Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum Isolates in India▿ †

Mixson-Hayden, Tonya; Jain, Vidhan; McCollum, Andrea M.; Poe, Amanda; Nagpal, Avinash C.; Dash, Aditya P.; Stiles, Jonathan K.; Udhayakumar, Venkatachalam; Singh, Neeru
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
656.5558%
Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first-line drugs used to treat malaria. Antimalarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum infection can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine- and antifolate drug-resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India, by genotyping the dhps, dhfr, pfmdr-1, and pfcrt genes using pyrosequencing, direct sequencing, and real-time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug-resistant genotypes in this area. Resistance to chloroquine was essentially fixed, with 95% of the isolates harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1 were found in 94%, 17%, and 77% of the isolates, respectively. Drug-resistant genotypes were equally likely to be associated with cerebral malaria as with mild malaria. We found evidence of a selective sweep in pfcrt and...

The Development of Ciprofloxacin Resistance in Pseudomonas aeruginosa Involves Multiple Response Stages and Multiple Proteins ▿ † ‡

Su, Hsun-Cheng; Ramkissoon, Kevin; Doolittle, Janet; Clark, Martha; Khatun, Jainab; Secrest, Ashley; Wolfgang, Matthew C.; Giddings, Morgan C.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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656.98164%
Microbes have developed resistance to nearly every antibiotic, yet the steps leading to drug resistance remain unclear. Here we report a multistage process by which Pseudomonas aeruginosa acquires drug resistance following exposure to ciprofloxacin at levels ranging from 0.5× to 8× the initial MIC. In stage I, susceptible cells are killed en masse by the exposure. In stage II, a small, slow to nongrowing population survives antibiotic exposure that does not exhibit significantly increased resistance according to the MIC measure. In stage III, exhibited at 0.5× to 4× the MIC, a growing population emerges to reconstitute the population, and these cells display heritable increases in drug resistance of up to 50 times the original level. We studied the stage III cells by proteomic methods to uncover differences in the regulatory pathways that are involved in this phenotype, revealing upregulation of phosphorylation on two proteins, succinate-semialdehyde dehydrogenase (SSADH) and methylmalonate-semialdehyde dehydrogenase (MMSADH), and also revealing upregulation of a highly conserved protein of unknown function. Transposon disruption in the encoding genes for each of these targets substantially dampened the ability of cells to develop the stage III phenotype. Considering these results in combination with computational models of resistance and genomic sequencing results...

Mutually Exclusive Genotypes for Pyrazinamide and 5-Chloropyrazinamide Resistance Reveal a Potential Resistance-Proofing Strategy▿

Baughn, Anthony D.; Deng, Jiaoyu; Vilchèze, Catherine; Riestra, Angelica; Welch, John T.; Jacobs, William R.; Zimhony, Oren
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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656.8975%
The pyrazinamide (PZA) analog 5-chloropyrazinamide (5-Cl PZA) is active against mycobacterial species, including PZA-resistant strains of Mycobacterium tuberculosis. In M. smegmatis, overexpression of the type 1 fatty acid synthase (FAS I) confers resistance to 5-Cl PZA, a potent FAS I inhibitor. Since M. tuberculosis and M. bovis cannot tolerate FAS I overexpression, 5-Cl PZA resistance mutations have yet to be described for tubercle bacilli. In an attempt to identify other factors that govern the activity of 5-Cl PZA, we selected for 5-Cl PZA-resistant isolates from a library of transposon-mutagenized M. smegmatis isolates. Here, we report that increased expression of the M. smegmatis pyrazinamidase PzaA confers resistance to 5-Cl PZA and susceptibility to PZA in M. smegmatis, M. tuberculosis, and M. bovis. In contrast, while ectopic overexpression of the M. tuberculosis pyrazinamidase PncA increases PZA susceptibility, this amidase does not mediate resistance to 5-Cl PZA. We conclude that PncA-independent turnover of 5-Cl PZA represents a potential mechanism of resistance to this compound for M. tuberculosis, which will likely translate into enhanced PZA susceptibility. Thus, countersusceptibility can be manipulated as a resistance-proofing strategy for PZA-based compounds when these agents are used simultaneously.

Analysis of the Functional Contributions of Asn233 in Metallo-β-Lactamase IMP-1 ▿

Brown, Nicholas G.; Horton, Lori B.; Huang, Wanzhi; Vongpunsawad, Sompong; Palzkill, Timothy
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2011 Português
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656.60625%
Metallo-β-lactamases, such as IMP-1, are a major global health threat, as they provide for bacterial resistance to a wide range of β-lactam antibiotics, including carbapenems. Understanding the molecular details of the enzymatic process and the sequence requirements for function are essential aids in overcoming β-lactamase-mediated resistance. An asparagine residue is conserved at position 233 in approximately 67% of all metallo-β-lactamases. Despite its conservation, the molecular basis of Asn233 function is poorly understood and remains controversial. It has previously been shown that mutations at this site exhibit context-dependent sequence requirements in that the importance of a given amino acid depends on the antibiotic being tested. To provide a more thorough examination as to the function and sequence requirements at this position, a collection of IMP-1 mutants encoding each of the 19 possible amino acid substitutions was generated. The resistance levels toward four β-lactam antibiotics were measured for Escherichia coli containing each of these mutants. The sequence requirements at position 233 for wild-type levels of resistance toward two cephalosporins were the most relaxed, while there were more stringent sequence requirements for resistance to ampicillin or imipenem. Enzyme kinetic analysis and determinations of steady-state protein levels indicated that the effects of the substitutions on resistance are due to changes in the kinetic parameters of the enzyme. Taken together...

Persistence of Transferable Extended-Spectrum-β-Lactamase Resistance in the Absence of Antibiotic Pressure

Cottell, Jennifer L.; Webber, Mark A.; Piddock, Laura J. V.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2012 Português
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656.63195%
The treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (blaCTX-M-14), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of the blaCTX-M-14 gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion...

Fks1 and Fks2 Are Functionally Redundant but Differentially Regulated in Candida glabrata: Implications for Echinocandin Resistance

Katiyar, Santosh K.; Alastruey-Izquierdo, Ana; Healey, Kelley R.; Johnson, Michael E.; Perlin, David S.; Edlind, Thomas D.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2012 Português
Relevância na Pesquisa
656.6837%
The echinocandins caspofungin, micafungin, and anidulafungin, inhibitors of cell wall β-1,3-glucan synthesis, were recently elevated to first-line agents for treating infections due to the azole-refractory yeast Candida glabrata. In Candida albicans, echinocandin resistance is strictly associated with mutations in Fks1, a large integral membrane protein and putative β-1,3-glucan synthase, while mutations in both Fks1 and its paralog Fks2 (but not Fks3) have been associated with resistance in C. glabrata. To further explore their function, regulation, and role in resistance, C. glabrata fks genes were disrupted and subjected to mutational analysis, and their differential regulation was explored. An fks1Δ fks2Δ double disruptant was not able to be generated; otherwise, all three single and remaining two double disruptants displayed normal growth and echinocandin susceptibility, indicating Fks1-Fks2 redundancy. Selection on echinocandin-containing medium for resistant mutants was dependent on strain background: only fks1Δ and fks1Δ fks3Δ strains consistently yielded mutants exhibiting high-level resistance, all with Fks2 hot spot 1 mutations. Thus, Fks1-Fks2 redundancy attenuates the rate of resistance; further analysis showed that it also attenuates the impact of resistance-conferring mutations. Growth of the fks1Δ and...

Systematic Review of Mutations in Pyrazinamidase Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis Clinical Isolates

Ramirez-Busby, Sarah M.; Valafar, Faramarz
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em 15/06/2015 Português
Relevância na Pesquisa
656.63195%
Pyrazinamide (PZA) is an important first-line drug in the treatment of tuberculosis (TB) and of significant interest to the HIV-infected community due to the prevalence of TB-HIV coinfection in some regions of the world. The mechanism of resistance to PZA is unlike that of any other anti-TB drug. The gene pncA, encoding pyrazinamidase (PZase), is associated with resistance to PZA. However, because single mutations in PZase have a low prevalence, the individual sensitivities are low. Hundreds of distinct mutations in the enzyme have been associated with resistance, while some only appear in susceptible isolates. This makes interpretation of molecular testing difficult and often leads to the simplification that any PZase mutation causes resistance. This systematic review reports a comprehensive global list of mutations observed in PZase and its promoter region in clinical strains, their phenotypic association, their global frequencies and diversity, the method of phenotypic determination, their MIC values when given, and the method of MIC determination and assesses the strength of the association between mutations and phenotypic resistance to PZA. In this systematic review, we report global statistics for 641 mutations in 171 (of 187) codons from 2...

Glyphosate resistance in barnyard grass (Echinochloa colona)

Thai, H.N.; Malone, J.M.; Boutsalis, P.; Preston, C.
Fonte: Weed Society of Victoria Inc.; Melbourne, Victoria Publicador: Weed Society of Victoria Inc.; Melbourne, Victoria
Tipo: Conference paper
Publicado em //2012 Português
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657.01414%
Echinochloa colona is an important summer-growing weed species in northern Australian cropping regions. As a result of the intensive use of glyphosate in summer fallows, glyphosate resistant populations of E. colona have evolved, with the number of resistant populations identified rapidly growing. This study identified glyphosate resistance in E. colona collected from different locations in Australia and investigated the mechanism of glyphosate resistance. Pot trials conducted on populations ofE. colona collected from northern Australia identified resistance to glyphosate in 11 populations of this weed species. The level of resistance varied among the populations from 2- to 11-fold. Sequencing of the target-site (EPSPS) identified a mutation at position 106 leading to a change from proline to serine in the most resistant population A533.1 only. With the range of resistance levels identified, it is expected that different mechanisms of resistance will be present among the rest of the resistant populations.; Hoan Nguyen Thai, Jenna Malone, Peter Boutsalis and Christopher Presto

Delayed Development of Linezolid Resistance in Staphylococcus aureus following Exposure to Low Levels of Antimicrobial Agents▿

Miller, Keith; O'Neill, Alexander J.; Wilcox, Mark H.; Ingham, Eileen; Chopra, Ian
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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The development of resistance to linezolid (LZD) in gram-positive bacteria depends on the mutation of a single 23S rRNA gene, followed by homologous recombination and gene conversion of the other alleles. We sought to inhibit this process in Staphylococcus aureus using a range of antibacterial agents, including some that suppress recombination. A model for the rapid selection of LZD resistance was developed which allowed the selection of LZD-resistant mutants with G2576T mutations in all five copies of the 23S rRNA gene following only 5 days of subculture. The emergence of LZD-resistant isolates was delayed by exposing cultures to low concentrations of various classes of antibiotics. All antibiotic classes were effective in delaying the selection of LZD-resistant mutants and, with the exception of fusidic acid (FUS) and rifampin (RIF), prolonged the selection window from 5 to ∼15 days. Inhibitors of DNA processing were no more effective than any other class of antibiotics at suppressing resistance development. However, the unrelated antimicrobials FUS and RIF were particularly effective at preventing the emergence of LZD resistance, prolonging the selection window from 5 to 25 days. The enhanced suppressive effect of FUS and RIF on the development of LZD resistance was lost in a recA-deficient host...