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19 results on '"Baylay, Alison J."'

9. Clinically relevant fluoroquinolone resistance due to constitutive overexpression of the PatAB ABC transporter in Streptococcus pneumoniae is conferred by disruption of a transcriptional attenuator

Author

Baylay, Alison J. and Piddock, Laura J. V.

Subjects
antimicrobial resistance mechanisms, regulation, Gene Expression Regulation, Bacterial, efflux, Anti-Bacterial Agents, Streptococcus pneumoniae, multidrug resistance, Transcription Termination, Genetic, Drug Resistance, Bacterial, Mutation, Humans, ATP-Binding Cassette Transporters, Original Research, Fluoroquinolones
Abstract

Objectives Constitutive overexpression of patAB has been observed in several unrelated fluoroquinolone-resistant laboratory mutants and clinical isolates; therefore, we sought to identify the cause of this overexpression. Methods Constitutive patAB overexpression in two clinical isolates and a laboratory-selected mutant was investigated using a whole-genome transformation approach. To determine the effect of the detected terminator mutations, the WT and mutated patA leader sequences were cloned upstream of a GFP reporter. Finally, mutation of the opposing base in the stem–loop structure was carried out. Results We identified three novel mutations causing up-regulation of patAB. All three of these were located in the upstream region of patA and affected the same Rho-independent transcriptional terminator structure. Each mutation was predicted to destabilize the terminator stem–loop to a different degree, and there was a strong correlation between predicted terminator stability and patAB expression level. Using a GFP reporter of patA transcription, these terminator mutations led to increased transcription of a downstream gene. For one mutant sequence, terminator stability could be restored by mutation of the opposing base in the stem–loop structure, demonstrating that transcriptional suppression of patAB is mediated by the terminator stem–loop structure. Conclusions This study showed that a mutation in a Rho-independent transcriptional terminator structure confers overexpression of patAB and fluoroquinolone resistance. Understanding how levels of the PatAB efflux pump are regulated increases our knowledge of pneumococcal biology and how the pneumococcus can respond to various stresses, including antimicrobials.

Published
2014

11. Desert dust as a source of iron to the globally important diazotroph Trichodesmium

Author

Polyviou, Despo, Baylay, Alison J., Hitchcock, Andrew, Robidart, Julie, Moore, C.M., Bibby, Thomas S., Polyviou, Despo, Baylay, Alison J., Hitchcock, Andrew, Robidart, Julie, Moore, C.M., and Bibby, Thomas S.

Abstract

The marine cyanobacterium Trichodesmium sp. accounts for approximately half of the annual ‘new’ nitrogen introduced to the global ocean but its biogeography and activity is often limited by the availability of iron (Fe). A major source of Fe to the open ocean is Aeolian dust deposition in which Fe is largely comprised of particles with reduced bioavailability over soluble forms of Fe. We report that Trichodesmium erythraeum IMS101 has improved growth rate and photosynthetic physiology and down-regulates Fe-stress biomarker genes when cells are grown in the direct vicinity of, rather than physically separated from, Saharan dust particles as the sole source of Fe. These findings suggest that availability of non-soluble forms of dust-associated Fe may depend on cell contact. Transcriptomic analysis further reveals unique profiles of gene expression in all tested conditions, implying that Trichodesmium has distinct molecular signatures related to acquisition of Fe from different sources. Trichodesmium thus appears to be capable of employing specific mechanisms to access Fe from complex sources in oceanic systems, helping to explain its role as a key microbe in global biogeochemical cycles.

Published
2018

15. The Comprehensive Antibiotic Resistance Database

Author

McArthur, Andrew G., primary, Waglechner, Nicholas, additional, Nizam, Fazmin, additional, Yan, Austin, additional, Azad, Marisa A., additional, Baylay, Alison J., additional, Bhullar, Kirandeep, additional, Canova, Marc J., additional, De Pascale, Gianfranco, additional, Ejim, Linda, additional, Kalan, Lindsay, additional, King, Andrew M., additional, Koteva, Kalinka, additional, Morar, Mariya, additional, Mulvey, Michael R., additional, O'Brien, Jonathan S., additional, Pawlowski, Andrew C., additional, Piddock, Laura J. V., additional, Spanogiannopoulos, Peter, additional, Sutherland, Arlene D., additional, Tang, Irene, additional, Taylor, Patricia L., additional, Thaker, Maulik, additional, Wang, Wenliang, additional, Yan, Marie, additional, Yu, Tennison, additional, and Wright, Gerard D., additional

Published
2013
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17. Molecular mechanisms of antibiotic resistance.

Author

Blair, Jessica M. A., Webber, Mark A., Baylay, Alison J., Ogbolu, David O., and Piddock, Laura J. V.

Subjects
ANTIBIOTICS, DRUG accessibility, PREVENTIVE medicine, BIOSYNTHESIS, PHYTONCIDES
Abstract

Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics. [ABSTRACT FROM AUTHOR]

Published
2015
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18. Overexpression of patA and patB, Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae

Author

Garvey, Mark I., Baylay, Alison J., Wong, Ryan L., and Piddock, Laura J. V.

Abstract

Fifty-seven clinical isolates of Streptococcus pneumoniae were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes patA and patB, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing patA and patB accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of patA and patB by in vitro mariner mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the patAB-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of patA and patB in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.

Published
2010

19. Overexpression of patAand patB, Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae

Author

Garvey, Mark I., Baylay, Alison J., Wong, Ryan L., and Piddock, Laura J. V.

Abstract

ABSTRACTFifty-seven clinical isolates of Streptococcus pneumoniaewere divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes patAand patB, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing patAand patBaccumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of patAand patBby in vitro marinermutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the patAB-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of patAand patBin clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.

Published
2010
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