scholarly journals In vitro selection of resistance in Streptococcus pneumoniae at in vivo fluoroquinolone concentrations

2009 ◽  
Vol 63 (4) ◽  
pp. 721-727 ◽  
Author(s):  
E. De Vecchi ◽  
L. Nicola ◽  
F. Ossola ◽  
L. Drago
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Selection Of ◽  
Selection Of Resistance

scholarly journals In Vitro Selection of Resistance to Four β-Lactams and Azithromycin in Streptococcus pneumoniae

1998 ◽  
Vol 42 (11) ◽  
pp. 2914-2918 ◽  
Author(s):  
Glenn A. Pankuch ◽  
Shane A. Jueneman ◽  
Todd A. Davies ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Antimicrobial Agents ◽  
Penicillin G ◽  
Resistance Selection ◽  
Resistant Strains ◽  
Selection Of ◽  
Selection Of Resistance

ABSTRACT Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 μg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 μg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 μg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 μg/ml) for three of the six strains, with MICs of other β-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 μg/ml to 0.125 to 0.5 μg/ml) for all six strains without significantly altering the MICs of other β-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect β-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for β-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 μg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 μg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 μg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin containedermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

scholarly journals Topoisomerase Mutations Associated with In Vitro Selection of Resistance to Moxifloxacin in Streptococcus pneumoniae

2002 ◽  
Vol 46 (8) ◽  
pp. 2712-2715 ◽  
Author(s):  
Serge Houssaye ◽  
Laurent Gutmann ◽  
Emmanuelle Varon
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Second Step ◽  
Wild Type ◽  
Topoisomerase Iv ◽  
Selection Step ◽  
Gyra Mutation ◽  
Selection Of ◽  
Selection Of Resistance

ABSTRACT We analyzed the frequencies of selection, the order of acquisition, and the mutations selected on moxifloxacin in two wild-type pneumococcal strains, R6 and 5714. The first selection step showed either a single GyrA mutation or no mutation in any of the quinolone resistance-determining regions. Second-step mutants selected had either a second mutation in ParC or in ParE. Moxifloxacin could belong to these fluoroquinolones, which preferentially target GyrA though probably acting equally through both gyrase and topoisomerase IV.

scholarly journals In vitro selection of resistance in Escherichia coli and Klebsiella spp. at in vivo fluoroquinolone concentrations

2010 ◽  
Vol 10 (1) ◽  
pp. 119 ◽  
Author(s):  
Lorenzo Drago ◽  
Lucia Nicola ◽  
Roberto Mattina ◽  
Elena De Vecchi
Keyword(s):  
Escherichia Coli ◽  
In Vitro Selection ◽  
Klebsiella Spp ◽  
Selection Of ◽  
Selection Of Resistance

The Effects of Shock Vancomycin Concentrations on the Formation of Heteroresistance in Staphylococcus aureus

2020 ◽  
Vol 65 (9-10) ◽  
pp. 3-7
Author(s):  
V. V. Gostev ◽  
Yu. V. Sopova ◽  
O. S. Kalinogorskaya ◽  
M. E. Velizhanina ◽  
I. V. Lazareva ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vitro Selection ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Concentration ◽  
Short Term ◽  
High Concentrations ◽  
Selection Of ◽  
Selection Of Resistance ◽  
Test Cultures

Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

In vitro selection of resistance to sofosbuvir in HCV replicons of genotype 1 to 6

2017 ◽  
Vol 22 (7) ◽  
pp. 587-597 ◽  
Author(s):  
Simin Xu ◽  
Brian Doehle ◽  
Sonal Rajyaguru ◽  
Bin Han ◽  
Ona Barauskas ◽  
...  
Keyword(s):  
In Vitro Selection ◽  
Genotype 1 ◽  
Selection Of ◽  
Selection Of Resistance

scholarly journals In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides

2005 ◽  
Vol 56 (4) ◽  
pp. 633-642 ◽  
Author(s):  
H. Carsenti-Dellamonica ◽  
M. Galimand ◽  
F. Vandenbos ◽  
C. Pradier ◽  
P. M. Roger ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Penicillin G ◽  
Selection Of

scholarly journals Robotic QM/MM-driven maturation of antibody combining sites

2016 ◽  
Vol 2 (10) ◽  
pp. e1501695 ◽  
Author(s):  
Ivan V. Smirnov ◽  
Andrey V. Golovin ◽  
Spyros D. Chatziefthimiou ◽  
Anastasiya V. Stepanova ◽  
Yingjie Peng ◽  
...  
Keyword(s):  
Immune Response ◽  
In Vitro Selection ◽  
Single Point ◽  
Combinatorial Libraries ◽  
Single Point Mutation ◽  
Wild Type ◽  
Selection Of ◽  
Maturation Function

In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.

In vitro Selection of a Peptide with High Selectivity for Cardiomyocytes In vivo

2004 ◽  
Vol 342 (1) ◽  
pp. 171-182 ◽  
Author(s):  
Michael J. McGuire ◽  
Kausar N. Samli ◽  
Stephen Albert Johnston ◽  
Kathlynn C. Brown
Keyword(s):  
In Vitro Selection ◽  
High Selectivity ◽  
Selection Of
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