scholarly journals Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities ofClostridium perfringensStrains

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Miseon Park ◽  
Fatemeh Rafii
Keyword(s):  
Fluoroquinolone Resistance ◽  
Phenotypic Characterization ◽  
Global Changes ◽  
Phenotype Microarray ◽  
Altered Expression ◽  
Chemical Structures ◽  
Resistance Selection ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Metabolic Activities

Fluoroquinolone resistance affects toxin production ofClostridium perfringensstrains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, fourC. perfringensstrains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria.

scholarly journals Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species

2006 ◽  
Vol 50 (7) ◽  
pp. 2323-2329 ◽  
Author(s):  
Tatiana Bogdanovich ◽  
Kathy A. Smith ◽  
Catherine Clark ◽  
Glenn A. Pankuch ◽  
Gengrong Lin ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Ribosomal Protein ◽  
Peptide Deformylase ◽  
Resistance Selection ◽  
Haemophilus Species ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Protein Mutations ◽  
Time Kill

ABSTRACT When tested against 254 Haemophilus influenzae strains, LBM415, a peptide deformylase inhibitor, gave MIC50 and MIC90 values of 2.0 μg/ml and 8.0 μg/ml, respectively. The MICs were independent of β-lactam or quinolone susceptibility and the presence or absence of macrolide efflux or ribosomal protein mutations. The MICs of LBM415 against 23 H. parainfluenzae strains were similar to those against H. influenzae. In contrast, erythromycin, azithromycin, and clarithromycin gave unimodal MIC distributions, and apart from β-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the β-lactams tested. Apart from selected quinolone-resistant strains, all strains were susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The potencies of all drugs against 23 H. parainfluenzae strains were similar to those against H. influenzae. Time-kill studies with 10 Haemophilus strains showed LBM415 to be bactericidal at 2× the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and β-lactams were bactericidal against 8 to 10 strains each at 2× the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2× the MIC after 24 h. Against six H. influenzae strains, postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep resistance selection studies, LBM415 produced resistant clones in 7 of the 10 strains tested, with MICs ranging from 4 to 64 μg/ml. No mutations in deformylase (def) and formyltransferase (fmt) genes were detected in any of the LBM415-resistant mutants.

scholarly journals Antistaphylococcal Activity of DX-619, a New Des-F(6)-Quinolone, Compared to Those of Other Agents

2005 ◽  
Vol 49 (8) ◽  
pp. 3325-3333 ◽  
Author(s):  
Tatiana Bogdanovich ◽  
Duygu Esel ◽  
Linda M. Kelly ◽  
Bülent Bozdogan ◽  
Kim Credito ◽  
...  
Keyword(s):  
Single Step ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Resistance Selection ◽  
Antistaphylococcal Activity ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Resistant Mutants

ABSTRACT The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC50s/MIC90s (μg/ml) against 131 Staphylococcus aureus strains (≤0.002 to 2.0/0.06/0.5) and 128 coagulase-negative staphylococci (0.004 to 0.25/0.016/0.125). Among strains tested, 76 S. aureus strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC50/MIC90 values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 μg/ml and sitafloxacin at 1.0 μg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32μ g/ml after <50 days of selection compared to 16 to> 32 μg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4× MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains.

scholarly journals Alcohol use disorder causes global changes in splicing in the human brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Derek Van Booven ◽  
Mengying Li ◽  
J. Sunil Rao ◽  
Ilya O. Blokhin ◽  
R. Dayne Mayfield ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Human Brain ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Gene Set Enrichment Analysis ◽  
Splicing Factor ◽  
Central Nucleus ◽  
Global Changes ◽  
Aberrant Expression ◽  
Altered Expression

AbstractAlcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

scholarly journals Contribution of Target Gene Mutations and Efflux to Decreased Susceptibility of Salmonella enterica Serovar Typhimurium to Fluoroquinolones and Other Antimicrobials

2006 ◽  
Vol 51 (2) ◽  
pp. 535-542 ◽  
Author(s):  
Sheng Chen ◽  
Shenghui Cui ◽  
Patrick F. McDermott ◽  
Shaohua Zhao ◽  
David G. White ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Efflux Pump ◽  
Critical Role ◽  
Gene Mutations ◽  
Efflux Pumps ◽  
Fluoroquinolone Resistance ◽  
Naturally Occurring ◽  
Serovar Typhimurium ◽  
Resistant Mutants ◽  
Increased Susceptibility

ABSTRACT The mechanisms involved in fluoroquinolone resistance in Salmonella enterica include target alterations and overexpression of efflux pumps. The present study evaluated the role of known and putative multidrug resistance efflux pumps and mutations in topoisomerase genes among laboratory-selected and naturally occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 μg/ml were derived in vitro using serovar Typhimurium S21. These mutants also showed decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials, including tetracycline, chloramphenicol, and several β-lactams. The expression of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were substantially increased (≥2-fold) among the fluoroquinolone-resistant mutants. Increased expression was also observed, but to a lesser extent, with three other putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with ciprofloxacin MICs of ≥32 μg/ml. Deletion of acrAB or tolC in S21 and its fluoroquinolone-resistant mutants resulted in increased susceptibility to fluoroquinolones and other tested antimicrobials. In naturally occurring fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA double mutations (S83F D87N) with wild-type gyrA increased susceptibility >500-fold. These results indicate that a combination of topoisomerase gene mutations, as well as enhanced antimicrobial efflux, plays a critical role in the development of fluoroquinolone resistance in both laboratory-derived and naturally occurring quinolone-resistant serovar Typhimurium strains.

scholarly journals Antimicrobial Susceptibility of Shigella sonnei Isolates in Japan and Molecular Analysis of S. sonnei Isolates with Reduced Susceptibility to Fluoroquinolones

2005 ◽  
Vol 49 (3) ◽  
pp. 1203-1205 ◽  
Author(s):  
Kenji Hirose ◽  
Jun Terajima ◽  
Hidemasa Izumiya ◽  
Kazumichi Tamura ◽  
Eiji Arakawa ◽  
...  
Keyword(s):  
Nalidixic Acid ◽  
Molecular Analysis ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Shigella Sonnei ◽  
Fluoroquinolone Resistance ◽  
Resistant Strains

ABSTRACT We performed susceptibility testing with Shigella sonnei isolates from imported and domestic cases of infection in Japan during 2001 and 2002. Some S. sonnei isolates were resistant to nalidixic acid, tetracycline, and trimethoprim-sulfamethoxazole. Most of the nalidixic acid-resistant strains showed reduced susceptibility to fluoroquinolones but did not show fluoroquinolone resistance.

scholarly journals Molecular Epidemiology of Antimicrobial-Resistant Commensal Escherichia coli Strains in a Cohort of Newborn Calves

2005 ◽  
Vol 71 (11) ◽  
pp. 6680-6688 ◽  
Author(s):  
Deborah V. Hoyle ◽  
Catherine M. Yates ◽  
Margo E. Chase-Topping ◽  
Esther J. Turner ◽  
Sarah E. Davies ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Turning Point ◽  
Temporal Trends ◽  
Resistant Isolate ◽  
Phenotypic Characterization ◽  
Environmental Source ◽  
Newborn Calves ◽  
Resistant Strains ◽  
Multiple Strains ◽  
Common Combination

ABSTRACT Pulsed-field gel electrophoresis (PFGE) was used to investigate the dissemination and diversity of ampicillin-resistant (Ampr) and nalidixic acid-resistant (Nalr) commensal Escherichia coli strains in a cohort of 48 newborn calves. Calves were sampled weekly from birth for up to 21 weeks and a single resistant isolate selected from positive samples for genotyping and further phenotypic characterization. The Ampr population showed the greatest diversity, with a total of 56 different genotype patterns identified, of which 5 predominated, while the Nalr population appeared to be largely clonal, with over 97% of isolates belonging to just two different PFGE patterns. Distinct temporal trends were identified in the distribution of several Ampr genotypes across the cohort, with certain patterns predominating at different points in the study. Cumulative recognition of new Ampr genotypes within the cohort was biphasic, with a turning point coinciding with the housing of the cohort midway through the study, suggesting that colonizing strains were from an environmental source on the farm. Multiply resistant isolates dominated the collection, with >95% of isolates showing resistance to at least two additional antimicrobials. Carriage of resistance to streptomycin, sulfamethoxazole, and tetracycline was the most common combination, found across several different genotypes, suggesting the possible spread of a common resistance element across multiple strains. The proportion of Ampr isolates carrying sulfamethoxazole resistance increased significantly over the study period (P < 0.05), coinciding with a decline in the most common genotype pattern. These data indicate that calves were colonized by a succession of multiply resistant strains, with a probable environmental source, that disseminated through the cohort over time.

scholarly journals Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1527
Author(s):  
Miki Kawada-Matsuo ◽  
Mi Nguyen-Tra Le ◽  
Hitoshi Komatsuzawa
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Antibacterial Peptides ◽  
Low Concentrations ◽  
Component Systems ◽  
Two Component Systems ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
High Concentrations

Staphylococcus aureus is a bacterium that mainly colonizes the nasal cavity and skin. To colonize the host, it is necessary for S. aureus to resist many antibacterial factors derived from human and commensal bacteria. Among them are the bacteria-derived antimicrobial peptides (AMPs) called bacteriocins. It was reported that some two-component systems (TCSs), which are signal transduction systems specific to bacteria, are involved in the resistance to several bacteriocins in S. aureus. However, the TCS-mediated resistance is limited to relatively low concentrations of bacteriocins, while high concentrations of bacteriocins still exhibit antibacterial activity against S. aureus. To determine whether we could obtain highly bacteriocin-resistant mutants, we tried to isolate highly nisin A-resistant mutants by exposing the cells to sub-minimum inhibitory concentrations (MICs) of nisin A. Nisin A is one of the bacteriocins produced by Lactococcus lactis and is utilized as a food preservative worldwide. Finally, we obtained highly nisin A-resistant mutants with mutations in one TCS, BraRS, and in PmtR, which is involved in the expression of pmtABCD. Notably, some highly resistant strains also showed increased pathogenicity. Based on our findings, this review provides up-to-date information on the role of TCSs in the susceptibility to antibacterial peptides. Additionally, the mechanism for high antimicrobial peptides resistance and its association with pathogenicity in S. aureus is elucidated.

scholarly journals C-Protein α-Antigen Modulates the Lantibiotic Thusin Resistance in Streptococcus Agalactiae

2021 ◽  
Author(s):  
Nemanja Mirkovic ◽  
Mina Obradovic ◽  
Paula M. O’Connor ◽  
Brankica Filipic ◽  
Branko Jovcic ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Sequence Analysis ◽  
Streptococcus Agalactiae ◽  
Protein A ◽  
Random Mutagenesis ◽  
Comparative Sequence Analysis ◽  
Receptor Protein ◽  
C Protein ◽  
Resistant Strains ◽  
Resistant Mutants

Abstract Screening for producers of potent antimicrobial peptides, resulted in the isolation of Bacillus cereus BGNM1 with strong antimicrobial activity against Listeria monocytogenes. Genome sequence analysis revealed that BGNM1 contains the gene cluster associated with the production of the lantibiotic, thusin, previously identified in B. thuringiensis. Purification of the antimicrobial activity confirmed that strain BGMN1 produces thusin. Both thusin sensitive and resistant strains were detected among clinical isolates of Streptococcus agalactiae. Random mutagenesis of a thusin sensitive strain, S. agalactiae B782, was performed in an attempt to identify the receptor protein for thusin. Three independent thusin resistant mutants were selected and their complete genomes sequenced. Comparative sequence analysis of these mutants with the WT strain revealed that duplication of a region encoding a 79 amino acids repeat in a C-protein a-antigen was a common difference, suggesting it to be responsible for increased resistance to thusin. Since induced thusin resistant mutants showed higher level of resistance than the naturally resistant B761 strain, complete genome sequencing of strain B761 was performed to check the integrity of the C-protein a-antigen-encoding gene. This analysis revealed that this gene is deleted in B761, providing further evidence that this protein promotes interaction of the thusin with receptor.

scholarly journals Streptococcus suis in Brazil: Genotypic, Virulence, and Resistance Profiling of Strains Isolated from Pigs between 2001 and 2016

Pathogens ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 31 ◽  
Author(s):  
Carlos E. C. Matajira ◽  
Luisa Z. Moreno ◽  
Andre P. Poor ◽  
Vasco T. M. Gomes ◽  
Andressa C. Dalmutt ◽  
...  
Keyword(s):  
Streptococcus Suis ◽  
Multidrug Resistant ◽  
Swine Industry ◽  
Pfge Typing ◽  
Resistance Selection ◽  
Important Challenge ◽  
Resistant Strains ◽  
Resistance Rates ◽  
Isolation Period

Streptococcus suis remains an important challenge for the worldwide swine industry. Considering that Brazil is a major pork producer and exporter, proper monitoring of the pathogen and resistance rates are required. We present here the characterization of Brazilian S. suis strains isolated over a 15 year period by pulsed-field gel electrophoresis (PFGE) typing, capsular, virulence, and antimicrobial resistance profiling. Serotype prevalence revealed a predominance of serotype 2/½ followed by 3, 7, 1/14, 6, 8, 18, 28, and 27; the latter had not yet been reported in Brazil. Resistance profiling enabled the differentiation of nine profiles presenting resistance to three and up to eight antimicrobial classes. Even though an association between the most resistant strains and isolation year starting from 2009 was observed, a high frequency of multidrug-resistant strains isolated from 2001 to 2003 was also detected. This suggests that despite the isolation period, S. suis strains already presented high resistance selection pressure. A slight association of serotype 2/½ with some virulence profiles and PFGE pulsotypes was also identified. Nevertheless, no clonal dispersion or persistency of clones over the analyzed years and herds was detected.

scholarly journals In Vitro Derivation of Fluoroquinolone-Resistant Mutants from Multiple Lineages of Haemophilus influenzae and Identification of Mutations Associated with Fluoroquinolone Resistance

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Hiroyuki Honda ◽  
Toyotaka Sato ◽  
Masaaki Shinagawa ◽  
Yukari Fukushima ◽  
Chie Nakajima ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Clinical Setting ◽  
Pathogenic Bacterium ◽  
Fluoroquinolone Resistance ◽  
Novel Mutations ◽  
Content Type ◽  
Resistant Mutants ◽  
High Level ◽  
Current Risk

ABSTRACT Haemophilus influenzae is a pathogenic bacterium that causes respiratory and otolaryngological infections. The increasing prevalence of β-lactamase–negative high-level ampicillin-resistant H. influenzae (high-BLNAR) is a clinical concern. Fluoroquinolones are alternative agents to β-lactams. However, the emergence and increasing prevalence of fluoroquinolone-resistant H. influenzae have been reported. The current risk of fluoroquinolone resistance in H. influenzae (especially in high-BLNAR) has not yet been evaluated. Here, we examined the development of fluoroquinolone resistance in fluoroquinolone-susceptible clinical H. influenzae isolates in vitro during passaging in the presence of moxifloxacin (from 0.03 to 128 mg/liter). Twenty-nine isolates were examined. Seventeen isolates (58.6%) showed reduced moxifloxacin susceptibility, and 10 of these 17 isolates (34.5% of all isolates) exceeded the Clinical and Laboratory Standards Institute breakpoint for moxifloxacin (MIC of >1 mg/liter) after repeat cultivation on moxifloxacin-containing agar. Seven of these ten isolates were high-BLNAR and represented multiple lineages. We identified 56 novel mutations in 45 genes induced during the development of fluoroquinolone resistance, except the defined quinolone resistance-determining regions (Ser84Leu and Asp88Tyr/Gly/Asn in GyrA and Gly82Asp, Ser84Arg, and Glu88Lys in ParC). Glu153Leu and ΔGlu606 in GyrA, Ser467Tyr and Glu469Asp in GyrB, and ompP2 mutations were novel mutations contributing to fluoroquinolone resistance in H. influenzae. In conclusion, H. influenzae clinical isolates from multiple lineages can acquire fluoroquinolone resistance by multiple novel mutations. The higher rate of derivation of fluoroquinolone-resistant H. influenzae from high-BLNAR than β-lactamase-negative ampicillin-susceptible isolates (P = 0.01) raises the possibility of the emergence and spread of fluoroquinolone-resistant high-BLNAR in the clinical setting.

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