scholarly journals In Vitro Activities of Garenoxacin (BMS-284756) against Haemophilus influenzae Isolates with Different Fluoroquinolone Susceptibilities

2003 ◽  
Vol 47 (11) ◽  
pp. 3539-3541 ◽  
Author(s):  
María Pérez-Vázquez ◽  
Federico Román ◽  
Belen Aracil ◽  
Rafael Cantón ◽  
José Campos
Keyword(s):  
Amino Acid ◽  
Haemophilus Influenzae ◽  
Amino Acid Change ◽  
Antimicrobial Agents ◽  
Acquired Resistance ◽  
Single Amino Acid ◽  
Intrinsic Activity ◽  
Single Amino Acid Change ◽  
Amoxicillin Clavulanate

ABSTRACT The in vitro activity of garenoxacin (BMS-284756) against 62 clinical Haemophilus influenzae isolates with different fluoroquinolone susceptibilities was determined by the microdilution susceptibility testing method and compared with the activities of other oral quinolones and nonquinolone oral antimicrobial agents. Cefixime presented the highest intrinsic activity (MIC at which 50% of the isolates tested were inhibited [MIC50], 0.01 μg/ml), followed by garenoxacin, moxifloxacin, and ciprofloxacin (MIC50, 0.06 μg/ml), levofloxacin (MIC50, 0.12 μg/ml), cefuroxime (MIC50, 1.0 μg/ml), and amoxicillin-clavulanate (MIC50, 1.0/0.5 μg/ml), amoxicillin (MIC50, 2 μg/ml), azithromycin (MIC50, 4 μg/ml), and erythromycin (MIC50, 8 μg/ml). In strains with ciprofloxacin MICs of ≤0.06 μg/ml, ciprofloxacin and garenoxacin displayed similar MIC50s and MIC90s, one dilution lower than those of moxifloxacin and levofloxacin. For strains for which ciprofloxacin MICs were ≥0.12 μg/ml, MIC50s were similar for the four quinolones tested, although garenoxacin presented the widest activity range (0.03 to 32 μg/ml) and the highest MIC at which 90% of the isolates tested were inhibited (16.0 μg/ml). For strains without amino acid changes in the quinolone resistance determining region (QRDR) of GyrA and ParC, garenoxacin MICs were ≤0.03 μg/ml; with a single amino acid change in GyrA, garenoxacin MICs were 0.06 to 0.12 μg/ml; with one amino acid change each in GyrA and ParC, garenoxacin MICs were 0.5 to 2.0 μg/ml; one amino acid change in ParC combined with two amino acid changes in GyrA increased the MICs to ≥4 μg/ml for all assayed quinolones. We conclude that garenoxacin has excellent activity against H. influenzae, although progressive acquired resistance was observed by step-by-step mutation in the QRDR of gyrA and parC.

scholarly journals Single amino acid changes in the mumps virus haemagglutinin–neuraminidase and polymerase proteins are associated with neuroattenuation

2009 ◽  
Vol 90 (7) ◽  
pp. 1741-1747 ◽  
Author(s):  
Tahir H. Malik ◽  
Candie Wolbert ◽  
Laura Nerret ◽  
Christian Sauder ◽  
Steven Rubin
Keyword(s):  
Amino Acid ◽  
Clinical Isolate ◽  
Amino Acid Change ◽  
Mumps Virus ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Supporting Evidence ◽  
L Protein ◽  
Single Amino Acid Change

It has previously been shown that three amino acid changes, one each in the fusion (F; Ala/Thr-91→Thr), haemagglutinin–neuraminidase (HN; Ser-466→Asn) and polymerase (L; Ile-736→Val) proteins, are associated with attenuation of a neurovirulent clinical isolate of mumps virus (88-1961) following serial passage in vitro. Here, using full-length cDNA plasmid clones and site-directed mutagenesis, it was shown that the single amino acid change in the HN protein and to a lesser extent, the change in the L protein, resulted in neuroattenuation, as assessed in rats. The combination of both amino acid changes caused neuroattenuation of the virus to levels previously reported for the clinical isolate following attenuation in vitro. The amino acid change in the F protein, despite having a dramatic effect on protein function in vitro, was previously shown to not be involved in the observed neuroattenuation, highlighting the importance of conducting confirmatory in vivo studies. This report provides additional supporting evidence for the role of the HN protein as a virulence factor and, as far as is known, is the first report to associate an amino acid change in the L protein with mumps virus neuroattenuation.

scholarly journals A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model

2017 ◽  
Vol 91 (15) ◽  
Author(s):  
Sujit K. Mohanty ◽  
Bryan Donnelly ◽  
Phylicia Dupree ◽  
Inna Lobeck ◽  
Sarah Mowery ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biliary Atresia ◽  
Amino Acid Change ◽  
Reverse Genetics ◽  
Single Amino Acid ◽  
Wild Type ◽  
Neonatal Mice ◽  
Single Amino Acid Change

ABSTRACT Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extrahepatic biliary tract and intrahepatic bile ducts. We previously showed that the amino acid arginine (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if this single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system. We demonstrated that the RRV mutant (RRVVP4-R446G) produced less symptomatology and replicated to lower titers both in vivo and in vitro than those seen with wild-type RRV, with reduced binding in cholangiocytes. Our results demonstrate that a single amino acid change in the RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in mice. IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in mice. We developed a reverse genetics system to create a mutant of RRV (RRVVP4-R446G) with a single amino acid change in the VP4 protein compared to that of wild-type RRV. In vitro, the mutant virus had reduced binding and infectivity in cholangiocytes. In vivo, it produced fewer symptoms and lower mortality in neonatal mice, resulting in an attenuated form of biliary atresia.

A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides

FEBS Letters ◽  
2000 ◽  
Vol 470 (2) ◽  
pp. 135-138 ◽  
Author(s):  
H. Vais ◽  
S. Atkinson ◽  
N. Eldursi ◽  
A.L. Devonshire ◽  
M.S. Williamson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sodium Channel ◽  
Amino Acid Change ◽  
Single Amino Acid ◽  
Pyrethroid Insecticides ◽  
Highly Sensitive ◽  
Single Amino Acid Change

Further characterization and determination of the single amino acid change in thetsI138reovirus thermosensitive mutant

2012 ◽  
Vol 58 (5) ◽  
pp. 589-595
Author(s):  
Guy Lemay ◽  
Martin Bisaillon
Keyword(s):  
Amino Acid ◽  
Amino Acid Change ◽  
Genetic Alterations ◽  
Biological Properties ◽  
Single Amino Acid ◽  
Temperature Sensitive ◽  
Nonpermissive Temperature ◽  
Gene Encoding ◽  
Viral Particles ◽  
Single Amino Acid Change

Many temperature-sensitive mutants have been isolated in early studies of mammalian reovirus. However, the biological properties and nature of the genetic alterations remain incompletely explored for most of these mutants. The mutation harbored by the tsI138 mutant was already assigned to the L3 gene encoding the λ1 protein. In the present study, this mutant was further studied as a possible tool to establish the role of the putative λ1 enzymatic activities in viral multiplication. It was observed that synthesis of viral proteins is only marginally reduced, while it was difficult to recover viral particles at the nonpermissive temperature. A single nucleotide substitution resulting in an amino acid change was found; the position of this amino acid is consistent with a probable defect in assembly of the inner capsid at the nonpermissive temperature.

scholarly journals Extreme Suppression of Lateral Floret Development by a Single Amino Acid Change in the VRS1 Transcription Factor

2017 ◽  
Vol 175 (4) ◽  
pp. 1720-1731 ◽  
Author(s):  
Shun Sakuma ◽  
Udda Lundqvist ◽  
Yusuke Kakei ◽  
Venkatasubbu Thirulogachandar ◽  
Takako Suzuki ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Amino Acid Change ◽  
Single Amino Acid ◽  
Lateral Floret ◽  
Single Amino Acid Change

scholarly journals A Single Amino Acid Change in the Newcastle Disease Virus Fusion Protein Alters the Requirement for HN Protein in Fusion

2000 ◽  
Vol 74 (11) ◽  
pp. 5101-5107 ◽  
Author(s):  
Theresa A. Sergel ◽  
Lori W. McGinnes ◽  
Trudy G. Morrison
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Protein Expression ◽  
Newcastle Disease ◽  
Amino Acid Change ◽  
Syncytium Formation ◽  
Single Amino Acid ◽  
Fusion Activity ◽  
Wild Type ◽  
Single Amino Acid Change

ABSTRACT The role of a leucine heptad repeat motif between amino acids 268 and 289 in the structure and function of the Newcastle disease virus (NDV) F protein was explored by introducing single point mutations into the F gene cDNA. The mutations affected either folding of the protein or the fusion activity of the protein. Two mutations, L275A and L282A, likely interfered with folding of the molecule since these proteins were not proteolytically cleaved, were minimally expressed at the cell surface, and formed aggregates. L268A mutant protein was cleaved and expressed at the cell surface although the protein migrated slightly slower than wild type on polyacrylamide gels, suggesting an alteration in conformation or processing. L268A protein was fusion inactive in the presence or absence of HN protein expression. Mutant L289A protein was expressed at the cell surface and proteolytically cleaved at better than wild-type levels. Most importantly, this protein mediated syncytium formation in the absence of HN protein expression although HN protein enhanced fusion activity. These results show that a single amino acid change in the F1 portion of the NDV F protein can alter the stringent requirement for HN protein expression in syncytium formation.

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