51 research outputs found

    Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use

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    The genetic basis for antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community in parallel with antimicrobial use. The results showed that fluoroquinolones, and not chloroquine as has been hypothesized elsewhere, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Jennie Crowe and Rebeccah Lijek are student co-authors. --author-supplied descriptio

    Quinolone resistance in Escherichia coli from Accra, Ghana

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    We documented for the first time the molecular basis for quinolone resistance in Ghana and the presence of horizontally disseminated genes conferring resistance to these drugs. --author-supplied descriptio

    Quinolone resistance in Escherichia coli from Accra, Ghana

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    <p>Abstract</p> <p>Background</p> <p>Antimicrobial resistance is under-documented and commensal <it>Escherichia coli </it>can be used as indicator organisms to study the resistance in the community. We sought to determine the prevalence of resistance to broad-spectrum antimicrobials with particular focus on the quinolones, which have recently been introduced in parts of Africa, including Ghana.</p> <p>Results</p> <p>Forty (13.7%) of 293 <it>E. coli </it>isolates evaluated were nalidixic acid-resistant. Thirteen (52%) of 2006 and 2007 isolates and 10 (66.7%) of 2008 isolates were also resistant to ciprofloxacin. All but one of the quinolone-resistant isolates were resistant to three or more other antimicrobial classes. Sequencing the quinolone-resistance determining regions of <it>gyrA </it>and <it>parC</it>, which encode quinolone targets, revealed that 28 quinolone-resistant <it>E. coli </it>harboured a substitution at position 83 of the <it>gyrA </it>gene product and 20 of these isolates had other <it>gyrA </it>and/or <it>parC </it>substitutions. Horizontally-acquired quinolone-resistance genes <it>qnrB1</it>, <it>qnrB2</it>, <it>qnrS1 </it>or <it>qepA </it>were detected in 12 of the isolates. In spite of considerable overall diversity among <it>E. coli </it>from Ghana, as evaluated by multilocus sequence typing, 15 quinolone-resistant <it>E. coli </it>belonged to sequence type complex 10. Five of these isolates carried <it>qnrS1 </it>alleles.</p> <p>Conclusions</p> <p>Quinolone-resistant <it>E. coli </it>are commonly present in the faecal flora of Accra residents. The isolates have evolved resistance through multiple mechanisms and belong to very few lineages, suggesting clonal expansion. Containment strategies to limit the spread of quinolone-resistant <it>E. coli </it>need to be deployed to conserve quinolone effectiveness and promote alternatives to their use.</p

    Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase Supports Mitochondrial Metabolism and Host-Cell Invasion ofTrypanosoma cruzi

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    Proline is crucial for energizing critical events throughout the life cycle of Trypanosoma cruzi, the etiological agent of Chagas disease. The proline breakdown pathway consists of two oxidation steps, both of which producereducing equivalents as follows: the conversion of proline to Δ1-pyrroline-5-carboxylate (P5C), and the subsequent conversion of P5C to glutamate. We have identified and characterized the Δ1-pyrroline-5-carboxylate dehydrogenase from T. cruzi (TcP5CDH) and report here on how this enzyme contributes to a central metabolic pathway in this parasite. Size-exclusionchromatography, two-dimensional gel electrophoresis, and small angle x-ray scattering analysis of TcP5CDH revealed an oligomericstate composed of two subunits of six protomers. TcP5CDH was found to complement a yeast strain deficient in PUT2 activity,confirming the enzyme's functional role; and the biochemical parameters (Km, kcat, and kcat/Km) of the recombinant TcP5CDH were determined, exhibiting values comparable with those from T. cruzi lysates. In addition, TcP5CDH exhibited mitochondrial staining during the main stages of the T. cruzi life cycle. mRNA and enzymatic activity levels indicated the up-regulation (6-fold change) of TcP5CDH during the infectivestages of the parasite. The participation of P5C as an energy source was also demonstrated. Overall, we propose that thisenzymatic step is crucial for the viability of both replicative and infective forms of T. cruzi

    Host-mediated interactions between bacterial pathogens of the upper respiratory tract

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    The mucosal surface of the upper respiratory tract is densely colonized with microorganisms, including many opportunistic pathogens such as S. pneumoniae, H. influenzae, and S. aureus . Colonization with a given species induces innate and adaptive immune responses in the host. These host responses can have far-reaching effects on other members of the microbial community, including other pathogens. Therefore, differential susceptibility to inflammation and immunity can result in the selection of certain microbial species and the elimination of others from the microbial community. By shaping the microbial landscape, these pathogen-host-pathogen interactions can influence disease outcome and transmission of major human pathogens. Here, we develop and employ animal models of co-colonization to elucidate the molecular mechanisms responsible for immune-mediated interactions between S. pneumoniae and H. influenzae, and S. pneumoniae and S. aureus. Specifically, we investigate how the innate immune response to colonization with H. influenzae affects S. pneumoniae using animal models and theoretical mathematical modeling. We demonstrate that inflammatory pressure exerted by co-colonizing H. influenzae selects for virulent S. pneumoniae capsule types during colonization. Our findings imply that immune-mediated interactions between H. influenzae and S. pneumoniae enhance the pathogenic potential of S. pneumoniae. We also investigate how the adaptive immune response to colonization with S. pneumoniae affects S. aureus colonization using a novel animal model that we develop. We demonstrate that antibody elicited by pneumococcal colonization cross-reacts with S. aureus and inhibits S. aureus colonization. We identify the antigens responsible for this cross-reactivity and show that they are necessary and sufficient to protect against S. aureus colonization. Our findings imply that immune-mediated interactions between S. pneumoniae and S. aureus inhibit S. aureus nasal colonization and thus reveal a novel paradigm for identifying protective antigens against S. aureus. Together, these studies illustrate how polymicrobial colonization of mucosal surfaces influences innate and adaptive immune response in the host, and vice versa. The study of immune-mediated interaction during colonization can provide novel insight into the outcome of bacterial colonization, disease progression, transmission, and evolution

    Preprint Peer Review Enhances Undergraduate Biology Students' Disciplinary Literacy and Sense of Belonging in STEM

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    ABSTRACT Education about scientific publishing and manuscript peer review is not universally provided in undergraduate science courses. Since peer review is integral to the scientific process and central to the identity of a scientist, we envision a paradigm shift where teaching peer review becomes integral to undergraduate science education. We hypothesize that teaching undergraduates how to peer review scientific manuscripts may facilitate their development of scientific literacy and identity formation. To this end, we developed a constructivist, service-learning curriculum for biology undergraduates to learn about the mechanisms of peer review using preprints and then to write and publish their own peer reviews of preprints as a way to authentically join the scientific community of practice. The curriculum was implemented as a semester-long intervention in one class and, in another class, as an embedded module intervention. Students' scientific literacy and peer review ability were assessed using quantitative methods. Student’s perceptions of their scientific literacy and identity were assessed using thematic analysis of students’ reflective writing. Here, we present data on the improvement in the peer review ability of undergraduates in both classes and data on the curriculum’s interrelated impact on students’ development of scientific literacy, identity, and belonging in peer and professional discourse spaces. These data suggest that undergraduates can and should be trained in peer review to foster the interrelated development of their scientific literacy, scientific identity, and sense of belonging in science

    Ecological consequences of ingestion of Bacillus cereus on Bacillus thuringiensis infections and on the gut flora of a lepidopteran host

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    The Bacillus cereus group comprises a diverse array of non-pathogenic bacteria as well as pathogens such as Bacillus thuringiensis. Their spores are found together in soil and leaves and are therefore likely to commonly interact within hosts. Mixed infections of pathogenic B. thuringiensis and non-pathogenic strains have been little studied, despite their potential impact on biological control and the evolutionary ecology of virulence. Antibiotic secreting strains of B. cereus have been shown to be able to synergize B. thuringiensis (Bt) infections. We explored the ecology of these mixed infections more broadly in the diamondback moth (DBM). We tested whether antibiotic-expressing B. cereus can synergize Bt infections initiated with spores, investigated whether ingestion of antibiotic-expressing B. cereus had any consequences for the larval gut flora and whether synergistic interactions with B. cereus increase Bt reproduction. Ingestion of high-antibiotic secreting B. cereus synergized infections of B. thuringiensis in diamondback moth larvae, but at a lower level than previously reported. Coinfection also increased slightly the number of Bt spores found in cadavers. Culture independent analysis of gut homogenates indicated that ingestion of an antibiotic-expressing strain of B. cereus reduced the abundance of the gut flora and led to gut communities being dominated bacteria with DGGE profiles very similar to pure B. cereus cultures. Ingestion of B. cereus, regardless of genotype, reduced densities of an enteric isolate of Enterobacter sp. These findings support the hypothesis that antibiotic secretion in the gut synergizes B. thuringiensis infections by reducing the abundance of the commensal gut flora and facilitating invasion by bacteria in the B. cereus group
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