scholarly journals Comparison of the Efficacies of Oral β-Lactams in Selection of Haemophilus influenzae Transformants with Mutated ftsI Genes

2008 ◽  
Vol 52 (5) ◽  
pp. 1880-1883 ◽  
Author(s):  
Sho Takahata ◽  
Yoshihisa Kato ◽  
Yumiko Sanbongi ◽  
Kazunori Maebashi ◽  
Takashi Ida
Keyword(s):  
Haemophilus Influenzae ◽  
Horizontal Transfer ◽  
Susceptible Strain ◽  
Genetic Transfer ◽  
Selection Window ◽  
Selection Of

ABSTRACT Horizontal transfer of the mutated ftsI gene from β-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae to a susceptible strain was examined in vitro under selection with nine oral β-lactams (ampicillin, amoxicillin, cefprozil, cefuroxime, cefpodoxime, cefdinir, cefcapene, cefditoren, and tebipenem). Compared to the penicillins and the carbapenem, the cephalosporins showed a wide selection window for the genetic transfer.

In Vitro Selection of RNA Aptamers Directed Against Protein E: A Haemophilus influenzae Adhesin

2014 ◽  
Vol 56 (8) ◽  
pp. 714-725 ◽  
Author(s):  
Anders Barfod ◽  
Birendra Singh ◽  
Urban Johanson ◽  
Kristian Riesbeck ◽  
Per Kjellbom
Keyword(s):  
Haemophilus Influenzae ◽  
In Vitro Selection ◽  
Rna Aptamers ◽  
Selection Of

scholarly journals Cotrimoxazole Prophylaxis Specifically Selects for Cotrimoxazole Resistance inStreptococcus mutansandStreptococcus sobrinuswith Varied Polymorphisms in the Target GenesfolAandfolP

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Buwembo William ◽  
Charles Mugisha Rwenyonyi ◽  
Göte Swedberg ◽  
Fred Kironde
Keyword(s):  
Mutans Streptococci ◽  
Streptococcus Sobrinus ◽  
Genetic Transfer ◽  
Cotrimoxazole Prophylaxis ◽  
Sulfonamide Drug ◽  
Prophylaxis Group ◽  
Folate Pathway ◽  
Reference Sequences ◽  
Selection Of

The selection of antibiotic resistance by cotrimoxazole prophylaxis was evaluated, and we characterized the mechanism of cotrimoxazole resistance inStreptococcus mutansandStreptococcus sobrinus.In vitrosusceptibility to six antibiotics was evaluated on 64 mutans streptococci group (MSG) isolates from a cotrimoxazole prophylaxis group and compared to 84 MSG isolates from a nonprophylaxis group. ThefolAandfolPgenes were sequenced and compared with reference sequences at NCBI. Only resistance to cotrimoxazole was significantly higher in the prophylaxis group (54.7% versus 15.5%,OR=6.59, 95% CI: 2.89–15.3,P<0.05). Resistance to amoxicillin, ceftriaxone, chloramphenicol, erythromycin, and tetracycline was 1.4%, 25.5%, 6.2%, 6.5%, and 29.6% of the isolates, respectively. Considerable polymorphisms were found in thefolPgene inS. mutans, but this could not be linked to sulfonamide drug resistance. No variation was seen infolPorfolAgenes ofS. sobrinus. Genetic transfer of folate pathway genes seems unlikely in these isolates.

scholarly journals Influence of Inoculum Size on the Selection of Resistant Mutants of Escherichia coli in Relation to Mutant Prevention Concentrations of Marbofloxacin

2007 ◽  
Vol 51 (11) ◽  
pp. 4163-4166 ◽  
Author(s):  
Aude Ferran ◽  
Véronique Dupouy ◽  
Pierre-Louis Toutain ◽  
Alain Bousquet-Mélou
Keyword(s):  
Escherichia Coli ◽  
Bacterial Population ◽  
Inoculum Size ◽  
Pharmacodynamic Model ◽  
Initial Size ◽  
Mutant Selection ◽  
Selection Window ◽  
Resistant Mutants ◽  
Selection Of

ABSTRACT We demonstrate using an in vitro pharmacodynamic model that the likelihood of selection of Escherichia coli mutants resistant to a fluoroquinolone was increased when the initial size of the bacterial population, exposed to fluoroquinolone concentrations within the mutant selection window, was increased.

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 β-lactams

2004 ◽  
Vol 49 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Catherine Clark ◽  
Klaudia Kosowska ◽  
Bülent Bozdogan ◽  
Kim Credito ◽  
Bonifacio Dewasse ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
In Vitro Selection ◽  
Selection Of ◽  
Selection Of Resistance

scholarly journals Horizontal Gene Transfer of ftsI, Encoding Penicillin-Binding Protein 3, in Haemophilus influenzae

2007 ◽  
Vol 51 (5) ◽  
pp. 1589-1595 ◽  
Author(s):  
Sho Takahata ◽  
Takashi Ida ◽  
Nami Senju ◽  
Yumiko Sanbongi ◽  
Aiko Miyata ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Haemophilus Influenzae ◽  
Binding Protein ◽  
Resistant Mutant ◽  
Penicillin Binding Protein ◽  
Genetic Transfer ◽  
Complete Sequences

ABSTRACT Horizontal gene transfer has been identified in only a small number of genes in Haemophilus influenzae, an organism which is naturally competent for transformation. This report provides evidence for the genetic transfer of the ftsI gene, which encodes penicillin-binding protein 3, in H. influenzae. Mosaic structures of the ftsI gene were found in several clinical isolates of H. influenzae. To identify the origin of the mosaic sequence, complete sequences of the corresponding gene from seven type strains of Haemophilus species were determined. Comparison of these sequences with mosaic regions identified a homologous recombination of the ftsI gene between H. influenzae and Haemophilus haemolyticus. Subsequently, ampicillin-resistant H. influenzae strains harboring identical ftsI sequences were genotyped by pulsed-field gel electrophoresis (PFGE). Divergent PFGE patterns among β-lactamase-nonproducing ampicillin-resistant (BLNAR) strains from different hospitals indicated the potential for the genetic transfer of the mutated ftsI gene between these isolates. Moreover, transfer of the ftsI gene from BLNAR strains to β-lactamase-nonproducing ampicillin-susceptible (BLNAS) H. influenzae strains was evaluated in vitro. Coincubation of a BLNAS strain (a rifampin-resistant mutant of strain Rd) and BLNAR strains resulted in the emergence of rifampin- and cefdinir-resistant clones at frequencies of 5.1 × 10−7 to 1.5 × 10−6. Characterization of these doubly resistant mutants by DNA sequencing of the ftsI gene, susceptibility testing, and genotyping by PFGE revealed that the ftsI genes of BLNAR strains had transferred to BLNAS strains during coincubation. In conclusion, horizontal transfer of the ftsI gene in H. influenzae can occur in an intraspecies and an interspecies manner.

scholarly journals Quinolone-Resistant Haemophilus influenzae: Determination of Mutant Selection Window for Ciprofloxacin, Garenoxacin, Levofloxacin, and Moxifloxacin

2004 ◽  
Vol 48 (11) ◽  
pp. 4460-4462 ◽  
Author(s):  
Xinying Li ◽  
Noriel Mariano ◽  
James J. Rahal ◽  
Carl M. Urban ◽  
Karl Drlica
Keyword(s):  
Haemophilus Influenzae ◽  
Wild Type ◽  
Mutant Selection ◽  
Stepwise Selection ◽  
Type Selection ◽  
Selection Window ◽  
Fourth Step ◽  
Selection Of

ABSTRACT Stepwise selection of ciprofloxacin-resistant Haemophilus influenzae mutants produced first-, second-, third-, and fourth-step substitutions in GyrA (S84Y), ParC (S84R), GyrA (D88N), and ParC (E88K), respectively. Successive mutations raised the mutant selection window. The wild-type selection window for garenoxacin, levofloxacin, and moxifloxacin was also measured.

Quinolone resistance is transferred horizontally via uptake signal sequence recognition in Haemophilus influenzae

2021 ◽  
Author(s):  
Emi Tanaka ◽  
Takeaki Wajima ◽  
Kei-ichi Uchiya ◽  
Hidemasa Nakaminami
Keyword(s):  
Amino Acid ◽  
Haemophilus Influenzae ◽  
Horizontal Transfer ◽  
Signal Sequence ◽  
Quinolone Resistance ◽  
Extracellular Dna ◽  
Amino Acid Substitutions ◽  
Sequence Recognition ◽  
Resistance Transfer

The presence of Haemophilus influenzae strains with low susceptibility to quinolones has been reported worldwide. However, the emergence and dissemination mechanisms remain unclear. In this study, a total of 14 quinolone-low-susceptible H. influenzae isolates were investigated phylogenetically and in vitro resistance transfer assay in order to elucidate the emergence and dissemination mechanisms. The phylogenetic analysis based on gyrA sequences showed that strains with the same sequence type determined by multilocus sequence typing were classified into different clusters, suggesting that H. influenzae quinolone resistance emerges not only by point mutation, but also by the horizontal transfer of mutated gyrA . Moreover, the in vitro resistance transfer assay confirmed the horizontal transfer of quinolone resistance and indicated an active role of extracellular DNA in the resistance transfer. Interestingly, the horizontal transfer of parC only occurred in those cells that harbored a GyrA with amino acid substitutions, suggesting a possible mechanism of quinolone resistance in clinical settings. Moreover, the uptake signal and uptake-signal-like sequences located downstream of the quinolone resistant-determining regions of gyrA and parC , respectively, contributed to the horizontal transfer of resistance in H. influenzae . Our study demonstrates that the quinolone resistance of H. influenzae could emerge due to the horizontal transfer of gyrA and parC via recognition of an uptake signal sequence or uptake-signal-like sequence. Since the presence of quinolone-low-susceptible H. influenzae with amino acid substitutions in GyrA have been increasing in recent years, it is necessary to focus our attention to the acquisition of further drug resistance in these isolates.

scholarly journals In Vivo Validation of the Mutant Selection Window Hypothesis with Moxifloxacin in a Murine Model of Tuberculosis

2007 ◽  
Vol 51 (12) ◽  
pp. 4261-4266 ◽  
Author(s):  
Deepak Almeida ◽  
Eric Nuermberger ◽  
Sandeep Tyagi ◽  
William R. Bishai ◽  
Jacques Grosset
Keyword(s):  
Drug Exposure ◽  
Serum Concentrations ◽  
Mutant Selection ◽  
Drug Concentrations ◽  
Selection Window ◽  
Mutant Prevention Concentration ◽  
Resistant Mutants ◽  
Selection Of

ABSTRACT Combination therapy is the most effective strategy to prevent emergence of resistance during tuberculosis (TB) treatment. Another strategy, albeit theoretical, is to limit the time that drug concentrations fall in the “mutant selection window” (MSW) between the MIC and the mutant prevention concentration (MPC). Drug concentrations above the MPC prevent selective amplification of resistant mutants in vitro even with a single drug exposure. The MSW concept has been validated using fluoroquinolones against Mycobacterium tuberculosis in vitro but not in vivo. Using a mouse model in which serum moxifloxacin (MXF) concentrations were maintained above the MPC, we tested whether this strategy prevents selection of MXF-resistant mutants. Beginning 2 weeks after aerosol infection with M. tuberculosis, when the mean lung log10 CFU count was 7.9 ± 0.2, mice received either no treatment or MXF in the diet at 0.25% to approximate the conventional human dose or 1.5% to maintain serum concentrations above the MPC (8 μg/ml). After 56 days of treatment, lung CFU counts were 3.5 ± 0.8 and 0.9 ± 0.6 in 0.25% and 1.5% of the MXF-treated mice, respectively. In mice given 0.25% MXF, MXF-resistant mutants were selected by day 28 and detected in 16% (3/19) of mice tested on day 56. No selection of MXF-resistant mutants was detected in mice given 1.5% MXF. We conclude that maintaining serum concentrations of MXF above the MPC prevents selection of MXF-resistant mutants. Although this target cannot be achieved clinically with MXF, it might be possible with new fluoroquinolones with more potent activity and/or improved pharmacokinetics.

Ultrastructural studies on the interaction of haemophilus influenzae with human endothelial cells in vitro

1990 ◽  
Vol 48 (3) ◽  
pp. 636-637
Author(s):  
D.J.P. Ferguson ◽  
M. Virji ◽  
H. Kayhty ◽  
E.R. Moxon
Keyword(s):  
Endothelial Cells ◽  
Haemophilus Influenzae ◽  
Intercellular Junctions ◽  
Blood Stream ◽  
Ultrastructural Studies ◽  
Endothelial Barriers ◽  
Serotype B ◽  
Meningitis In Children ◽  
Respiratory Epithelial

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.

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