scholarly journals A novelqacAallele results in an elevated chlorhexidine glu conate minimum inhibitory concentration in cutaneousStaphylococcus epidermidisisolates

2018 ◽  
Author(s):  
Amin Addetia ◽  
Alexander L Greninger ◽  
Amanda Adler ◽  
Shuhua Yuan ◽  
Negar Makhsous ◽  
...  

AbstractChlorhexidine gluconate (CHG) is a topical antiseptic widely used in healthcare settings. InStaphylococcusspp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneousStaphylococcusisolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed 63 (6%) of these isolates had elevated CHG MICs (≥ 4 μg/mL). Screening of all 1,050 isolates forqacA/Bby restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novelqacA/BRFLP pattern,qacAB273. The CHG MIC was significantly higher forqacAB273-positive isolates (MIC50: 4 μg/mL, [range: 0.5 – 4 μg/mL]) compared to otherqacgroups:qacA-positive (n=559, 1 μg/mL, [0.5 – 4 μg/mL]),qacB-positive (n=17, 1 μg/mL, [0.25 – 2 μg/mL]), andqacA/B-negative (n=418, 1 μg/mL, [0.125 – 2 μg/mL], p=0.001). TheqacAB273-positive isolates also displayed a high proportion of methicillin resistance (96.4%) compared to otherqacgroups (24.9 – 61.7%, p=0.001). Whole genome sequencing revealed thatqacAB273-positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, namedqacA4, was carried on the novel plasmid pAQZ1. TheqacA4-carrying isolates belonged to the highly resistantS. epidermidisclone ST2 and were collected from multiple centers across the United States and Canada. Curing an isolate ofqacA4resulted in a four-fold decrease in the CHG MIC, confirming the role ofqacA4in the elevated CHG MIC. Our results highlight the importance of further studyingqacA4and its functional role in clinical staphylococci.ImportanceStaphylococcus epidermidisis an important cause of infections in patients with implanted devices. Bathing with chlorhexidine gluconate (CHG), a topical antiseptic, has been shown to reduce rates of device-associated infections, especially those caused byS. epidermidis. InS. epidermidis, reduced susceptibility to CHG is associated with carriage of theqacAgene. As part of a multicenter CHG bathing trial, we obtained cutaneousStaphylococcusisolates from pediatric oncology patients across the United States and Canada. We identified a group of isolates capable of surviving in higher concentrations of CHG and determined a novel allele ofqacA, termedqacA4and carried on the novel plasmid pAQZ1, was responsible for the isolates’ survival in higher CHG concentrations. TheqacA4-carryingS. epidermidisisolates belonged to the highly resistant and virulent ST2 clonal type. Our results highlight the need to understand the global distribution of novelqacAalleles, includingqacA4, and their mechanistic effect on efflux.

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Amin Addetia ◽  
Alexander L. Greninger ◽  
Amanda Adler ◽  
Shuhua Yuan ◽  
Negar Makhsous ◽  
...  

ABSTRACTChlorhexidine gluconate (CHG) is a topical antiseptic widely used in health care settings. InStaphylococcusspp., the pump QacA effluxes CHG, while the closely related QacB cannot due to a single amino acid substitution. We characterized 1,050 cutaneousStaphylococcusisolates obtained from 173 pediatric oncology patients enrolled in a multicenter CHG bathing trial. CHG susceptibility testing revealed that 63 (6%) of these isolates had elevated CHG MICs (≥4 μg/ml). Screening of all 1,050 isolates for theqacA/Bgene (the sameqacgene with A or B allele) by restriction fragment length polymorphism (RFLP) yielded 56 isolates with a novelqacA/BRFLP pattern,qacA/B273. The CHG MIC was significantly higher forqacA/B273-positive isolates (MIC50, 4 μg/ml; MIC range, 0.5 to 4 μg/ml) than for otherqacgroups:qacA-positive isolates (n = 559; MIC50, 1 μg/ml; MIC range, 0.5 to 4 μg/ml),qacB-positive isolates (n = 17; MIC50, 1 μg/ml; MIC range, 0.25 to 2 μg/ml), andqacA/B-negative isolates (n = 418, MIC50, 1 μg/ml; MIC range, 0.125 to 2 μg/ml) (P = 0.001). A high proportion of theqacA/B273-positive isolates also displayed methicillin resistance (96.4%) compared to the otherqacgroups (24.9 to 61.7%) (P = 0.001). Whole-genome sequencing revealed thatqacA/B273-positive isolates encoded a variant of QacA with 2 amino acid substitutions. This new allele, namedqacA4, was carried on the novel plasmid pAQZ1. TheqacA4-carrying isolates belonged to the highly resistantStaphylococcus epidermidissequence type 2 clone. By searching available sequence data sets, we identified 39 additionalqacA4-carryingS. epidermidisstrains from 5 countries. Curing an isolate ofqacA4resulted in a 4-fold decrease in the CHG MIC, confirming the role ofqacA4in the elevated CHG MIC. Our results highlight the importance of further studyingqacA4and its functional role in clinical staphylococci.


Author(s):  
Deirdre David

In the mid- to late 1950s, Pamela emerged as a critically acclaimed novelist, particularly after the family returned to London. In perhaps her best-known novel, The Unspeakable Skipton, she explores the life of a paranoid writer who sponges on English visitors to Bruges. The novel was hailed for its wit and sensitive depiction of the life of a writer. She also published a fine study of a London vicar martyred in marriage to a vain and selfish wife: The Humbler Creation is remarkable for its incisive and empathetic depiction of male despair. The Last Resort sealed her distinction as a brilliant novelist of domestic life in its frank depiction of male homosexuality. While continuing to publish fiction, Pamela maintained her reputation as a deft reviewer. In 1954, she and Charles travelled to the United States—the first of many trips that were to follow.


2005 ◽  
Vol 79 (17) ◽  
pp. 11412-11421 ◽  
Author(s):  
Chang-Won Lee ◽  
David E. Swayne ◽  
Jose A. Linares ◽  
Dennis A. Senne ◽  
David L. Suarez

ABSTRACT In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular criteria for classification as a highly pathogenic AIV was isolated from chickens in the state of Texas in the United States. However, clinical manifestations in the affected flock were consistent with avian influenza caused by a low-pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04 [TX/04]) was not virulent for experimentally inoculated chickens. The hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered from chickens in Texas in 2002. However, the TX/04 isolate had one additional basic amino acid at the HA cleavage site, which could be attributed to a single point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had sequence of a clearly different origin. The TX/04 isolate also had a stalk deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing viruses constructed by in vitro mutagenesis followed by reverse genetics, we found that the pathogenicity of the TX/04 virus could be increased in vitro and in vivo by the insertion of an additional basic amino acid at the HA cleavage site and not by the loss of a glycosylation site near the cleavage site. Our study provides the genetic and biologic characteristics of the TX/04 isolate, which highlight the complexity of the polygenic nature of the virulence of influenza viruses.


PMLA ◽  
2009 ◽  
Vol 124 (1) ◽  
pp. 25-43 ◽  
Author(s):  
Timothy Aubry

This essay considers the American reception of Khaled Hosseini's The Kite Runner in the context of the Bush administration's global war on terrorism by examining the customer reviews of the novel posted on Amazon. As many of the responses indicate, identification serves as a paradoxical means of negotiating with fictional representations of foreignness. The intense and painful empathy inspired by The Kite Runner serves a valorizing function for American readers, strengthening their sense of their own humanity—an effect that resists strict political categorization. Hosseini's ambivalent conception of what it means to be human, I argue, supports a diversity of competing attitudes toward the United States' military intervention in the Middle East and central Asia, while simultaneously catering to fantasies of escape from ideological and cultural divisions altogether.


Author(s):  
Genoveffa Giambona ◽  

The purpose of this article is to analyse Roddy Doyle’s representations of Irishness and Ireland in Oh, Play That Thing (2004). The novel is the second instalment in Doyle’s The Last Roundup Trilogy, a historical fiction describing the making of the Irish nation through the adventures and misadventures of Henry Smart, its protagonist. In the novel, constructions of Irishness are projected onto the outside world through Henry’s picaresque travels in the United States. The article examines how Irishness is constructed in the book and how it becomes intertwined with identity construction in other minority groups.


Author(s):  
S.M. Mahan ◽  
B.H. Simbi ◽  
M.J. Burridge

White-tailed deer are susceptible to heartwater (Ehrlichia [Cowdria] ruminantium infection) and are likely to suffer high mortality if the disease spreads to the United States. It is vital, therefore, to validate a highly specific and sensitive detection method for E. ruminantium infection that can be reliably used in testing white-tailed deer, which are reservoirs of antigenically or genetically related agents such as Ehrlichia chaffeensis, Anaplasma (Ehrlichia) phagocytophilum (HGE agent) and Ehrlichia ewingii. Recently, a novel but as yet unnamed ehrlichial species, the white-tailed deer ehrlichia (WTDE), has been discovered in deer populations in the United States. Although the significance of WTDE as a pathogen is unknown at present, it can be distinguished from other Ehrlichia spp. based on 16S rRNA gene sequence analysis. In this study it was differentiated from E. ruminantium by the use of the pCS20 PCR assay which has high specificity and sensitivity for the detection of E. ruminantium. This assay did not amplify DNA from the WTDE DNA samples isolated from deer resident in Florida, Georgia and Missouri, but amplified the specific 279 bp fragment from E. ruminantium DNA. The specificity of the pCS20 PCR assay for E. ruminantium was confirmed by Southern hybridization. Similarly, the 16S PCR primers (nested) that amplify a specific 405-412 bp fragment from the WTDE DNA samples, did not amplify any product from E. ruminantium DNA. This result demonstrates that it would be possible to differentiate between E. ruminantium and the novel WTDE agent found in white tailed deer by applying the two respective PCR assays followed by Southern hybridizations. Since the pCS20 PCR assay also does not amplify any DNA products from E. chaffeensis or Ehrlichia canis DNA, it is therefore the method of choice for the detection of E. ruminantium in these deer and other animal hosts.


Lateral ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Kristin Moriah

Kristin Moriah’s essay is rooted in extensive archival work in the US and Germany, examining the transatlantic circulation of Uncle Tom’s Cabin through markets of performance and literature in and between Germany and the United States. The essay follows the performative tropes of Uncle Tom’s Cabin from its originary political resonances to the present-day restaurants, train-stops, and housing projects named for the novel. Moriah reveals how the figurations of blackness arising from these texts are foundational to the construction of Germanness and American-German relations in the early 20th century and beyond.


Parasite ◽  
2021 ◽  
Vol 28 ◽  
pp. 22 ◽  
Author(s):  
Eric Tielemans ◽  
Tomoko Otsuki ◽  
Tara Cheesman ◽  
Fiona Selmes ◽  
Anthony Pfefferkorn ◽  
...  

Esafoxolaner is a purified afoxolaner enantiomer with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in a novel topical endectoparasiticide formulation for cats. This novel formulation was tested in four field studies, in the United States, Europe, Japan and Australia. In all studies, naturally flea-infested domestic cats were treated with the novel formulation at the label dose and conditions of use. The main objective, identical in the four studies, was to assess efficacy on fleas, based on comparison of mean number of fleas found on infested cats before and one month after treatment. Tolerance to the product was also evaluated in the four studies. Otherwise, the studies had some differences in their design and secondary objectives, for example testing for a reduction in flea infestation-related cutaneous signs, testing of one treatment or of three monthly treatments, and use of a positive control group. In the four studies, a total of 307 cats were treated with the novel formulation. The reduction of fleas one month after treatment was 97.7%, 98.8%, 100% and 99.7% in the United States, Europe, Japan and Australia, respectively. There were no significant health abnormalities attributed to treatment in any of the studies.


Design Issues ◽  
2022 ◽  
Vol 38 (1) ◽  
pp. 17-28
Author(s):  
Lauren Downing Peters

Abstract This article considers the possibilities and limitations of plus-size clothing— a subcategory of ready-to-wear that is deeply embedded in the history of dieting, exercise, standardized sizing, and the industrialization of clothing manufacturing in the United States. In doing so, it draws on fashion theory and disability theory in exposing how plus-size clothing functions as a normalizing mechanism, thereby inhibiting innovation in this sector. The article concludes with a counterexploration of the possibilities of “fat clothes” and the novel w ays of seeing and existing in the world that they might enable.


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