# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 5985 | 0 | 1.0000 | Alternative quinolone-resistance pathway caused by simultaneous horizontal gene transfer in Haemophilus influenzae. BACKGROUND: Quinolone-resistant bacteria are known to emerge via the accumulation of mutations in a stepwise manner. Recent studies reported the emergence of quinolone low-susceptible Haemophilus influenzae ST422 isolates harbouring two relevant mutations, although ST422 isolates harbouring one mutation were never identified. OBJECTIVES: To investigate if GyrA and ParC from quinolone low-susceptible isolates can be transferred horizontally and simultaneously to susceptible isolates. METHODS: Genomic DNA was extracted from an H. influenzae isolate harbouring amino acid substitutions in both gyrA and parC and mixed with clinical isolates. The emergence of resistant isolates was compared, and WGS analysis was performed. RESULTS: By adding the genomic DNA harbouring both mutated gyrA and parC, resistant bacteria exhibiting recombination at gyrA only or both gyrA and parC loci were obtained on nalidixic acid and pipemidic acid plates, and the frequency was found to increase with the amount of DNA. Recombination events in gyrA only and in both gyrA and parC occurred with at least 1 and 1-100 ng of DNA, respectively. The genome sequence of a representative strain showed recombination events throughout the genome. The MIC of quinolone for the resulting strains was found to be similar to that of the donor. Although the recombination efficacy was different among the various strains, all strains used in this study obtained multiple genes simultaneously. CONCLUSIONS: These findings indicate that H. influenzae can simultaneously obtain more than two mutated genes. This mechanism of horizontal transfer could be an alternative pathway for attaining quinolone resistance. | 2022 | 36124853 |
| 5987 | 1 | 0.9998 | Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in epidemiological unrelated Stenotrophomonas maltophilia clinical isolates. Clinical strains of Stenotrophomonas maltophilia are often highly resistant to multiple antibiotics and this resistance is steadily rising. Quinolones are included in the group of antimicrobial agents to which this microorganism is developing resistance. Therefore, the aim of this study was to analyze the epidemiological relationship among 22 clinical isolates of S. maltophilia as well as the molecular mechanisms responsible for the acquisition of quinolone-resistance in these strains. The results of the pulsed-field gel electrophoresis (PFGE) showed an heterogenicity of 82% among the strains used in the study. On the other hand, no amino acid changes were found in the quinolone resistance-determining region (QRDR) of either gyrA and parC genes among quinolone-susceptible and -resistant S. maltophilia strains. Besides, the amino acid of the GyrA found in the position equivalent to Ser-83 of E. coli was Gln instead of a Ser or Thr, the amino acids usually encountered in this position among Gram-negative bacteria. The results suggest that there is not a relationship between the presence of this Gln and the resistance to quinolones in S. maltophilia. We can conclude that, contrary to what has been described in other microorganisms, in these S. maltophilia isolates, the development of resistance to quinolones was not related to mutations in the QRDR of gyrA and parC genes. Thus, to our knowledge, this is the first report describing this phenomenon. | 2002 | 12523620 |
| 5977 | 2 | 0.9998 | Methods to determine antibiotic resistance gene silencing. The occurrence of antibiotic-resistant bacteria is an increasingly serious problem world-wide. In addition, to phenotypically resistant bacteria, a threat may also be posed by isolates with silent, but intact, antibiotic resistance genes. Such isolates, which have recently been described, possess wild-type genes that are not expressed, but may convert to resistance by activating expression of the silent genes. They may therefore compromise the efficacy of antimicrobial treatment, particularly if their presence has not been diagnosed. This chapter describes the detection of silent resistance genes by PCR and DNA sequencing. A method to detect five potentially silent acquired resistance genes; aadA, bla (OXA-2), strAB, sul1, and tet(A) is described. First, the susceptibility of the isolates to the relevant antibiotics is determined by an appropriate susceptibility testing method, such as E-test. Then the presence of the genes is investigated by PCR followed by agarose gel electrophoresis of the amplification products. If a resistance gene is detected in a susceptible isolate, the entire open-reading frame and promoter sequence of the gene is amplified by PCR and their DNA sequences obtained. The DNA sequences are then compared to those of known resistant isolates, to detect mutations that may account for susceptibility. If no mutations are detected the expression of the gene is investigated by RT-PCR following RNA extraction. The methods described here can be applied to all acquired resistance genes for which sequence and normal expression data are available. | 2010 | 20401584 |
| 5986 | 3 | 0.9998 | Transferable fluoroquinolone resistance in Enterobacteriaceae and Pseudomonas aeruginosa isolated from hemocultures. BACKGROUND: The main mechanisms causing high-level resistance to fluoroquinolones (FQ) are encoded chromosomally; that includes mutations in genes coding DNA-gyrase, but overexpression of efflux pumps contributes to increased minimum inhibitory concentration (MIC) of FQ as well. However, genes responsible for FQ-resistance may be harboured in transferable/conjugative plasmids. For some time, there was an assumption that resistance to FQ cannot be transferable in conjugation due to their synthetic origin, until 1998, when plasmid-mediated resistance transmission in Klebsiella pneumoniae was proved. We aimed to detect the occurrence of transferable FQ-resistance among Gram- negative bacteria isolated from patients in Czech and Slovak hospitals. METHODS: In this study, we tested 236 clinical isolates of Gram-negative bacteria for transferable resistance. Among relevant isolates we performed PCR detection of transferable fluoroquinolone genes (qnr). RESULTS: We have observed transfer of determinants of cephalosporin-resistance, aminoglycoside resistance as well as FQ-resistance (in 10 cases; 4.24%) not only intra-species but inter-species too. The presence of qnr gene was detected in two isolates of forty tested (5%). We have also observed that determinants of cephalosporin-resistance and aminoglycoside-resistance were linked to those of FQ-resistance and were transferred en block in conjugation. CONCLUSION: We have proved that resistance to fluoroquinolones can be transferred horizontally via conjugation among Gram-negative bacteria of different species and is associated with resistance to other antibiotics. | 2014 | 24844110 |
| 5979 | 4 | 0.9998 | Mutations in gyrA, gyrB, parC, and parE in quinolone-resistant strains of Neisseria gonorrhoeae. Mutations in the genes for the subunits GyrA and ParC of the target enzymes DNA gyrase and topoisomerase IV are important mechanisms of resistance in quinolone-resistant bacteria, including Neisseria gonorrhoeae. The target enzymes also consist of the subunits GyrB and ParE, respectively, though their role in quinolone-resistance has not been fully investigated. We sequenced the quinolone-resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE in 25 ciprofloxacin-resistant strains from Bangladesh (MIC 4-->32 mg/l) and 5 susceptible strains of N. gonorrhoeae. All the resistant strains had three or four mutations. Two of these were at positions 91 and 95 of gyrA. Fourteen strains had an additional mutation in parC at position 91, and 17 strains had an additional mutation in parE in position 439. No alterations were found in gyrB. The five susceptible strains had identical DNA sequences. Data indicate that the mutations detected in the QRDR of gyrA and parC may be important in the development of quinolone resistance. According to transformation experiments we assume that the alteration in parE is not related to a high degree of quinolone resistance. There was no correlation between ciprofloxacin MICs and pattern or number of mutations in the target genes. | 2002 | 12529019 |
| 5972 | 5 | 0.9998 | Method of Selection of Bacteria Antibiotic Resistance Genes Based on Clustering of Similar Nucleotide Sequences. A new method for selection of bacterium antibiotic resistance genes is proposed and tested for solving the problems related to selection of primers for PCR assay. The method implies clustering of similar nucleotide sequences and selection of group primers for all genes of each cluster. Clustering of resistance genes for six groups of antibiotics (aminoglycosides, β-lactams, fluoroquinolones, glycopeptides, macrolides and lincosamides, and fusidic acid) was performed. The method was tested for 81 strains of bacteria of different genera isolated from patients (K. pneumoniae, Staphylococcus spp., S. agalactiae, E. faecalis, E. coli, and G. vaginalis). The results obtained by us are comparable to those in the selection of individual genes; this allows reducing the number of primers necessary for maximum coverage of the known antibiotic resistance genes during PCR analysis. | 2017 | 29063318 |
| 5973 | 6 | 0.9998 | DNA microarray detection of antimicrobial resistance genes in diverse bacteria. High throughput genotyping is essential for studying the spread of multiple antimicrobial resistance. A test oligonucleotide microarray designed to detect 94 antimicrobial resistance genes was constructed and successfully used to identify antimicrobial resistance genes in control strains. The microarray was then used to assay 51 distantly related bacteria, including Gram-negative and Gram-positive isolates, resulting in the identification of 61 different antimicrobial resistance genes in these bacteria. These results were consistent with their known gene content and resistance phenotypes. Microarray results were confirmed by polymerase chain reaction and Southern blot analysis. These results demonstrate that this approach could be used to construct a microarray to detect all sequenced antimicrobial resistance genes in nearly all bacteria. | 2006 | 16427254 |
| 5981 | 7 | 0.9998 | Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. A 4.2-kb DNA fragment conferring quinolone resistance was cloned from a quinolone-resistant clinical isolate of Staphylococcus aureus and was shown to possess a part of the grlB gene and a mutated grlA gene. S-80-->F and E-84-->K mutations in the grlA gene product were responsible for the quinolone resistance. The mutated grlA genes responsible for quinolone resistance were dominant over the wild-type allele, irrespective of gene dosage in a transformation experiment with the grlA gene alone. However, dominance by mutated grlA genes depended on gene dosage when bacteria were transformed with the grlA and grlB genes in combination. Quinolone-resistant gyrA mutants were easily isolated from a strain, S. aureus RN4220, carrying a plasmid with the mutated grlA gene, though this was not the case for other S. aureus strains lacking the plasmid. The elimination of this plasmid from such quinolone-resistant gyrA mutants resulted in marked increases in quinolone susceptibility. These results suggest that both DNA gyrase and DNA topoisomerase IV may be targets of quinolones and that the quinolone susceptibility of organisms may be determined by which of these enzymes is most quinolone sensitive. | 1996 | 8723458 |
| 5984 | 8 | 0.9998 | First characterization of fluoroquinolone resistance in Streptococcus suis. We have identified and sequenced the genes encoding the quinolone-resistance determining region (QRDR) of ParC and GyrA in fluoroquinolone-susceptible and -resistant Streptococcus suis clinical isolates. Resistance is the consequence of single point mutations in the QRDRs of ParC and GyrA and is not due to clonal spread of resistant strains or horizontal gene transfer with other bacteria. | 2007 | 17116660 |
| 5769 | 9 | 0.9998 | Analysis of Nucleotide Sequences Similarity and Protein Prediction of Some Resistance Genes in Escherichia coli Isolated from Iraqi Patients with Urinary Tract Infections. Antibiotic resistance leads to a dramatic increase in the morbidity and mortality caused by infectious diseases. Even though estimates vary widely, the economic cost of antimicrobial-resistant bacteria is on a rise. The current aimed to identify the antimicrobial resistance of Escherichia coli (E. coli). In fact, this study focused on the recent deep-learning methods (sequencing) to investigate E. coli antibiotic resistance and their protein sequences. To evaluate antibiotic resistance, the sequencing method could be considered the method of choice. The E. coli was identified by either specific biochemical tests or polymerase chain reaction (PCR) using the 16S rRNA gene. The results of aadA1 gene sequences demonstrated 10 nucleic acid substitutions throughout, as compared to the reference NCBI database (MG385063). Out of the 10 nucleic acid substitutions, 9 missense effects were observed. While the dfrA1 gene sequences illustrated 20 nucleic acid substitutions throughout, compared to the reference NCBI database (KY706080), out of the 20 nucleic acid substitutions, 8 missense effects were observed. Furthermore, the sul1 gene sequences displayed 20 nucleic acid substitutions throughout, in comparison with the reference NCBI database (CP069561), and out of the 20 nucleic acid substitutions, 12 missense effects were detected. The cat1 gene sequences showed 14 nucleic acid substitutions throughout, compared to the reference NCBI database (NC017660), and out of the 14 nucleic acid substitutions, 8 missense effects were observed. The precise point (Missense) mutation in four genes (aadA1, dfrA1, sul1, and cat1) in the expected sequence is interpreted to be the target site of a site-specific recombination mechanism that led to antibiotics resistance in E. coli isolates. | 2022 | 36618275 |
| 5836 | 10 | 0.9997 | Identification of Pseudomonas aeruginosa genes associated with antibiotic susceptibility. Pseudomonas aeruginosa causes acute and chronic infections in humans and these infections are difficult to treat due to the bacteria's high-level of intrinsic and acquired resistance to antibiotics. To address this problem, it is crucial to investigate the molecular mechanisms of antibiotic resistance in this organism. In this study, a P. aeruginosa transposon insertion library of 17000 clones was constructed and screened for altered susceptibility to seven antibiotics. Colonies grown on agar plates containing antibiotics at minimum inhibitory concentrations (MICs) and those unable to grow at 1/2 MIC were collected. The transposon-disrupted genes in 43 confirmed mutants that showed at least a three-fold increase or a two-fold decrease in susceptibility to at least one antibiotic were determined by semi-random PCR and subsequent sequencing analysis. In addition to nine genes known to be associated with antibiotic resistance, including mexI, mexB and mexR, 24 new antibiotic resistance-associated genes were identified, including a fimbrial biogenesis gene pilY1 whose disruption resulted in a 128-fold increase in the MIC of carbenicillin. Twelve of the 43 genes identified were of unknown function. These genes could serve as targets to control or reverse antibiotic resistance in this important human pathogen. | 2010 | 20953948 |
| 5976 | 11 | 0.9997 | fosM, a New Family of Fosfomycin Resistance Genes Identified in Bacterial Species Isolated from Human Microbiota. Fosfomycin is a decades-old antibiotic, currently reused because of its activity against multidrug-resistant bacteria. Here, we used a combined in vitro/in silico approach to search for fosfomycin resistance determinants in 25 new bacterial species isolated from the human microbiota. Putative resistance genes were cloned into a susceptible Escherichia coli strain. MIC values increased from 1 μg/ml to 1,024 μg/ml. Here, we report a new family of potential chromosomal fosfomycin resistance genes, named fosM. | 2021 | 33199384 |
| 6263 | 12 | 0.9997 | Gene-Gene Interactions Dictate Ciprofloxacin Resistance in Pseudomonas aeruginosa and Facilitate Prediction of Resistance Phenotype from Genome Sequence Data. Ciprofloxacin is one of the most widely used antibiotics for treating Pseudomonas aeruginosa infections. However, P. aeruginosa acquires mutations that confer ciprofloxacin resistance, making treatment more difficult. Resistance is multifactorial, with mutations in multiple genes influencing the resistance phenotype. However, the contributions of individual mutations and mutation combinations to the amounts of ciprofloxacin that P. aeruginosa can tolerate are not well understood. Engineering P. aeruginosa strain PAO1 to contain mutations in any one of the resistance-associated genes gyrA, nfxB, rnfC, parC, and parE showed that only gyrA mutations increased the MIC for ciprofloxacin. Mutations in parC and parE increased the MIC of a gyrA mutant, making the bacteria ciprofloxacin resistant. Mutations in nfxB and rnfC increased the MIC, conferring resistance, only if both were mutated in a gyrA background. Mutations in all of gyrA, nfxB, rnfC, and parC/E further increased the MIC. These findings reveal an epistatic network of gene-gene interactions in ciprofloxacin resistance. We used this information to predict ciprofloxacin resistance/susceptibility for 274 isolates of P. aeruginosa from their genome sequences. Antibiotic susceptibility profiles were predicted correctly for 84% of the isolates. The majority of isolates for which prediction was unsuccessful were ciprofloxacin resistant, demonstrating the involvement of additional as yet unidentified genes and mutations in resistance. Our data show that gene-gene interactions can play an important role in antibiotic resistance and can be successfully incorporated into models predicting resistance phenotype. | 2021 | 33875431 |
| 5978 | 13 | 0.9997 | Evidences of gentamicin resistance amplification in Klebsiella pneumoniae isolated from faeces of hospitalized newborns. The intestinal microbiota, a barrier to the establishment of pathogenic bacteria, is also an important reservoir of opportunistic pathogens. It plays a key role in the process of resistance-genes dissemination, commonly carried by specialized genetic elements, like plasmids, phages, and conjugative transposons. We obtained from strains of enterobacteria, isolated from faeces of newborns in a university hospital nursery, indication of phenotypical gentamicin resistance amplification (frequencies of 10(-3) to 10(-5), compatible with transposition frequencies). Southern blotting assays showed strong hybridization signals for both plasmidial and chromosomal regions in DNA extracted from variants selected at high gentamicin concentrations, using as a probe a labeled cloned insert containing aminoglycoside modifying enzyme (AME) gene sequence originated from a plasmid of a Klebsiella pneumoniae strain previously isolated in the same hospital. Further, we found indications of inactivation to other resistance genes in variants selected under similar conditions, as well as, indications of co-amplification of other AME markers (amikacin). Since the intestinal environment is a scenario of selective processes due to the therapeutic and prophylactic use of antimicrobial agents, the processes of amplification of low level antimicrobial resistance (not usually detected or sought by common methods used for antibiotic resistance surveillance) might compromise the effectiveness of antibiotic chemotherapy. | 1999 | 10585658 |
| 5980 | 14 | 0.9997 | Mutation in the gyrA gene of quinolone-resistant clinical isolates of Acinetobacter baumannii. The gyrA gene mutations associated with quinolone resistance were determined in 21 epidemiologically unrelated clinical isolates of Acinetobacter baumannii. Our studies highlight the conserved sequences in the quinolone resistance-determining region of the gyrA gene from A. baumannii and other bacteria. All 15 isolates for which the MIC of ciprofloxacin is > or = 4 micrograms/ml showed a change at Ser-83 to Leu. Six strains for which the MIC of ciprofloxacin is 1 microgram/ml did not show any change at Ser-83, although a strain for which the MIC of ciprofloxacin is 1 microgram/ml exhibited a change at Gly-81 to Val. Although it is possible that mutations in other locations of the gyrA gene, the gyrB gene, or in other genes may also contribute to the modulation of the MIC level, our results suggest that a gyrA mutation at Ser-83 is associated with quinolone resistance in A. baumannii. | 1995 | 7625818 |
| 6258 | 15 | 0.9997 | Alterations in GyrA and ParC associated with fluoroquinolone resistance in Enterococcus faecium. High-level quinolone resistance in Enterococcus faecium was associated with mutations in both gyrA and parC genes in 10 of 11 resistant strains. On low-level resistant strain without such mutations may instead possess an efflux mechanism or alterations in the other subunits of the gyrase or topoisomerase IV genes. These findings are similar to those for other gram-positive bacteria, such as Enterococcus faecalis. | 1999 | 10103206 |
| 5766 | 16 | 0.9997 | Ceftazidime resistance in Pseudomonas aeruginosa is multigenic and complex. Pseudomonas aeruginosa causes a wide range of severe infections. Ceftazidime, a cephalosporin, is a key antibiotic for treating infections but a significant proportion of isolates are ceftazidime-resistant. The aim of this research was to identify mutations that contribute to resistance, and to quantify the impacts of individual mutations and mutation combinations. Thirty-five mutants with reduced susceptibility to ceftazidime were evolved from two antibiotic-sensitive P. aeruginosa reference strains PAO1 and PA14. Mutations were identified by whole genome sequencing. The evolved mutants tolerated ceftazidime at concentrations between 4 and 1000 times that of the parental bacteria, with most mutants being ceftazidime resistant (minimum inhibitory concentration [MIC] ≥ 32 mg/L). Many mutants were also resistant to meropenem, a carbapenem antibiotic. Twenty-eight genes were mutated in multiple mutants, with dacB and mpl being the most frequently mutated. Mutations in six key genes were engineered into the genome of strain PAO1 individually and in combinations. A dacB mutation by itself increased the ceftazidime MIC by 16-fold although the mutant bacteria remained ceftazidime sensitive (MIC < 32 mg/L). Mutations in ampC, mexR, nalC or nalD increased the MIC by 2- to 4-fold. The MIC of a dacB mutant was increased when combined with a mutation in ampC, rendering the bacteria resistant, whereas other mutation combinations did not increase the MIC above those of single mutants. To determine the clinical relevance of mutations identified through experimental evolution, 173 ceftazidime-resistant and 166 sensitive clinical isolates were analysed for the presence of sequence variants that likely alter function of resistance-associated genes. dacB and ampC sequence variants occur most frequently in both resistant and sensitive clinical isolates. Our findings quantify the individual and combinatorial effects of mutations in different genes on ceftazidime susceptibility and demonstrate that the genetic basis of ceftazidime resistance is complex and multifactorial. | 2023 | 37192202 |
| 4498 | 17 | 0.9997 | A naturally occurring gene amplification leading to sulfonamide and trimethoprim resistance in Streptococcus agalactiae. Gene amplifications have been detected as a transitory phenomenon in bacterial cultures. They are predicted to contribute to rapid adaptation by simultaneously increasing the expression of genes clustered on the chromosome. However, genome amplifications have rarely been described in natural isolates. Through DNA array analysis, we have identified two Streptococcus agalactiae strains carrying tandem genome amplifications: a fourfold amplification of 13.5 kb and a duplication of 92 kb. Both amplifications were located close to the terminus of replication and originated independently from any long repeated sequence. They probably arose in the human host and showed different stabilities, the 13.5-kb amplification being lost at a frequency of 0.003 per generation and the 92-kb tandem duplication at a frequency of 0.035 per generation. The 13.5-kb tandem amplification carried the five genes required for dihydrofolate biosynthesis and led to both trimethoprim (TMP) and sulfonamide (SU) resistance. Resistance to SU probably resulted from the increased synthesis of dihydropteroate synthase, the target of this antibiotic, whereas the amplification of the whole pathway was responsible for TMP resistance. This revealed a new mechanism of resistance to TMP involving an increased dihydrofolate biosynthesis. This is, to our knowledge, the first reported case of naturally occurring antibiotic resistance resulting from genome amplification in bacteria. The low stability of DNA segment amplifications suggests that their role in antibiotic resistance might have been underestimated. | 2008 | 18024520 |
| 3601 | 18 | 0.9997 | R factors mediate resistance to mercury, nickel, and cobalt. Fifty-five clinical isolates and laboratory stocks of Escherichia coli and Salmonella were studied for resistance to each of ten metals. Eleven clinical isolates carrying R factors were resistant to mercury, and, in each case, the resistance was mediated by a previously undefined R-factor gene. The gene was phenotypically expressed within 2 to 4 minutes after entry into sensitive bacteria, but the basis for the resistance remains undefined. Fourteen strains, 12 infected with R factors, were resistant to cobalt and nickel, but these resistances were mediated by R-factor genes in only two strains; separate R-factor genes mediated the resistances to nickel and cobalt. These and other results indicate that the genetic composition of R factors is greater than that originally defined. | 1967 | 5337360 |
| 5650 | 19 | 0.9997 | High-level trimethoprim resistance in urinary bacteria. The results of a three year evaluation of the incidence and type of trimethoprim resistance in pathogens responsible for significant bacteriuria in a general hospital in Edinburgh UK, are presented and compared to results of a previous study. In the present study, trimethoprim resistance was 50% more frequent in bacteria isolated from men and nearly twice as frequent in bacteria from elderly patients. However, the proportion of trimethoprim resistant strains fell annually when resistance was measured at trimethoprim concentrations of both 10 mg/l and 1000 mg/l. The proportion of strains able to transfer trimethoprim resistance also fell by half, and there was some movement of trimethoprim resistance transposons into the bacterial chromosome. These results suggest that migration of high-level trimethoprim resistance genes into the permanent location of the bacterial chromosome is occurring. | 1986 | 3527699 |