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143 results on '"Baughn, Anthony D."'

1. Unique genomic sequences in a novel Mycobacterium avium subsp. hominissuis lineage enable fine scale transmission route tracing during pig movement

Author

Komatsu, Tetsuya, Ohya, Kenji, Ota, Atsushi, Nishiuchi, Yukiko, Yano, Hirokazu, Matsuo, Kayoko, Odoi, Justice Opare, Suganuma, Shota, Sawai, Kotaro, Hasebe, Akemi, Asai, Tetsuo, Yanai, Tokuma, Fukushi, Hideto, Wada, Takayuki, Yoshida, Shiomi, Ito, Toshihiro, Arikawa, Kentaro, Kawai, Mikihiko, Ato, Manabu, Baughn, Anthony D., Iwamoto, Tomotada, and Maruyama, Fumito

Published
2023
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13. Structure-Aware Mycobacterium tuberculosis Functional Annotation Uncloaks Resistance, Metabolic, and Virulence Genes

Author

Modlin, Samuel J., primary, Elghraoui, Afif, additional, Gunasekaran, Deepika, additional, Zlotnicki, Alyssa M., additional, Dillon, Nicholas A., additional, Dhillon, Nermeeta, additional, Kuo, Norman, additional, Robinhold, Cassidy, additional, Chan, Carmela K., additional, Baughn, Anthony D., additional, and Valafar, Faramarz, additional

Published
2021
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14. Genomic features of Mycobacterium avium subsp. hominissuis isolated from pigs in Japan

Author

Komatsu, Tetsuya, primary, Ohya, Kenji, additional, Ota, Atsushi, additional, Nishiuchi, Yukiko, additional, Yano, Hirokazu, additional, Matsuo, Kayoko, additional, Odoi, Justice Opare, additional, Suganuma, Shota, additional, Sawai, Kotaro, additional, Hasebe, Akemi, additional, Asai, Tetsuo, additional, Yanai, Tokuma, additional, Fukushi, Hideto, additional, Wada, Takayuki, additional, Yoshida, Shiomi, additional, Ito, Toshihiro, additional, Arikawa, Kentaro, additional, Kawai, Mikihiko, additional, Ato, Manabu, additional, Baughn, Anthony D, additional, Iwamoto, Tomotada, additional, and Maruyama, Fumito, additional

Published
2021
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15. The two-component regulatory system senX3-regX3 regulates phosphate-dependent gene expression in Mycobacterium smegmatis

Author

Glover, Robert T., Kriakov, Jordan, Garforth, Scott J., Baughn, Anthony D., and Jacobs, William R., Jr.

Subjects
Gene expression -- Research, Mycobacteria -- Genetic aspects, Mycobacteria -- Research, Mycobacterium -- Genetic aspects, Mycobacterium -- Research, Genetic regulation -- Research, Phosphates -- Research, Biological sciences
Abstract

Phosphate import is required for the growth of mycobacteria and is regulated by environmental inorganic phosphate ([P.sub.i]) concentrations, although the mechanism of this regulation has not been characterized. The expression of genes involved in [P.sub.i] acquisition is frequently regulated by two-component regulatory systems (2CRs) consisting of a sensor histidine kinase and a DNA-binding response regulator. In this work, we have identified the senX3-regX3 2CR as a [P.sub.i]-dependent regulator of genes involved in phosphate acquisition in Mycobacterium smegmatis. Characterization of senX3 mutants with different PhoA phenotypes suggests a dual role for SenX3 as a phosphatase or a phosphodonor for the response regulator RegX3, depending upon [P.sub.i] availability. Expression of PhoA activity required phosphorylation of RegX3, consistent with a role for phosphorylated RegX3 (RegX3~P) as a transcriptional activator of phoA. Furthermore, purified RegX3~P bound to promoter sequences from phoA, senX3, and the high-affinity phosphate transporter component pstS, demonstrating direct transcriptional control of all three genes. DNase I footprinting and primer extension analyses have further defined the DNA-binding region and transcriptional start site within the phoA promoter. A DNA motif consisting of an inverted repeat was identified in each of the promoters bound by RegX3~P. Based upon our findings, we propose a model for [P.sub.i]-regulated gene expression mediated by SenX3-RegX3 in mycobacteria.

Published
2007

17. The strict anaerobe Bacteroides fragilis grows in and benefits from nanomolar concentrations of oxygen

Author

Baughn, Anthony D. and Malamy, Michael H.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Anthony D. Baughn; Michael H. Malamy (corresponding author) Strict anaerobes cannot grow in the presence of greater than 5 µ M dissolved oxygen [1]. Despite this growth inhibition, many [...]

Published
2004
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27. Activity of 5-chloro-pyrazinamide in mice infected with Mycobacterium tuberculosis or Mycobacterium bovis

Author

Ahmad, Zahoor, Tyagi, Sandeep, Minkowski, Austin, Almeida, Deepak, Nuermberger, Eric L., Peck, Kaitlin M., Welch, John T., Baughn, Anthony D., Jacobs, Williams R., and Grosset, Jacques H.

Subjects
Mice, Mice, Inbred BALB C, pyrazinamide, Experimental chemotherapy, tuberculosis, Antitubercular Agents, Animals, Original Article, Female, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Mycobacterium bovis, mouse
Abstract

Background & objectives: Pyrazinamide is an essential component of first line anti-tuberculosis regimen as well as most of the second line regimens. This drug has a unique sterilizing activity against Mycobacterium tuberculosis. Its unique role in tuberculosis treatment has lead to the search and development of its structural analogues. One such analogue is 5-chloro-pyrazinamide (5-Cl-PZA) that has been tested under in vitro conditions against M. tuberculosis. The present study was designed with an aim to assess the activity of 5-Cl-PZA, alone and in combination with first-line drugs, against murine tuberculosis. Methods: The minimum inhibitory concentration (MIC) of 5-Cl-PZA in Middlebrook 7H9 broth (neutral pH) and the inhibitory titre of serum from mice that received a 300 mg/kg oral dose of 5-Cl-PZA 30 min before cardiac puncture were determined. To test the tolerability of orally administered 5-Cl-PZA, uninfected mice received doses up to 300 mg/kg for 2 wk. Four weeks after low-dose aerosol infection either with M. tuberculosis or M. bovis, mice were treated 5 days/wk with 5-Cl-PZA, at doses ranging from 37.5 to 150 mg/kg, either alone or in combination with isoniazid and rifampicin. Antimicrobial activity was assessed by colony-forming unit counts in lungs after 4 and 8 wk of treatment. Results: The MIC of 5-Cl-PZA against M. tuberculosis was between 12.5 and 25 μg/ml and the serum inhibitory titre was 1:4. Under the same experimental conditions, the MIC of pyrazinamide was >100 μg/ml and mouse serum had no inhibitory activity after a 300 mg/kg dose; 5-Cl-PZA was well tolerated in uninfected and infected mice up to 300 and 150 mg/kg, respectively. While PZA alone and in combination exhibited its usual antimicrobial activity in mice infected with M. tuberculosis and no activity in mice infected with M. bovis, 5-Cl-PZA exhibited antimicrobial activity neither in mice infected with M. tuberculosis nor in mice infected with M. bovis. Interpretation & conclusion: Our findings showed that 5-Cl-PZA at doses up to 150 mg/kg was not active in chronic murine TB model. Further studies need to be done to understand the mechanism and mode of inactivation in murine model of tuberculosis.

Published
2012

33. The essential role of fumarate reductase in haem-dependent growth stimulation of Bacteroides fragilis

Author

Baughn, Anthony D. and Malamy, Michael H.

Subjects
Anaerobic bacteria -- Physiological aspects, Anaerobic bacteria -- Genetic aspects, Gene expression -- Analysis, Heme -- Influence, Heme -- Physiological aspects, Biological sciences
Abstract

Research reveals the operon for the fumarate reductase contains three genes, including the haemoprotein in Bacteroides fragilis. The genes encode the cytochrome, iron-sulfur cluster protein and flavoprotein of the fumarate reductase. Data indicate that fumarate reductase is required for both energy metabolism and succinate biosynthesis in these bacteria.

Published
2003

35. Mutual potentiation drives synergy between trimethoprim and sulfamethoxazole.

Author

Yusuke Minato, Dawadi, Surendra, Kordus, Shannon L., Sivanandam, Abiram, Aldrich, Courtney C., and Baughn, Anthony D.

Subjects
CO-trimoxazole, TETRAHYDROFOLATE synthase, BIOSYNTHESIS, MYCOSES, FOLIC acid
Abstract

Trimethoprim (TMP)-sulfamethoxazole (SMX) is a widely used synergistic antimicrobial combination to treat a variety of bacterial and certain fungal infections. These drugs act by targeting sequential steps in the biosynthetic pathway for tetrahydrofolate (THF), where SMX inhibits production of the THF precursor dihydropteroate, and TMP inhibits conversion of dihydrofolate (DHF) to THF. Consequently, SMX potentiates TMP by limiting de novo DHF production and this mono-potentiation mechanism is the current explanation for their synergistic action. Here, we demonstrate that this model is insufficient to explain the potent synergy of TMP-SMX. Using genetic and biochemical approaches, we characterize a metabolic feedback loop in which THF is critical for production of the folate precursor dihydropterin pyrophosphate (DHPPP). We reveal that TMP potentiates SMX activity through inhibition of DHPPP synthesis. Our study demonstrates that the TMP-SMX synergy is driven by mutual potentiation of the action of each drug on the other. [ABSTRACT FROM AUTHOR]

Published
2018
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42. Binding Pocket Alterations in Dihydrofolate Synthase Confer Resistance to para -Aminosalicylic Acid in Clinical Isolates of Mycobacterium tuberculosis

Author

Zhao, Fei, primary, Wang, Xu-De, additional, Erber, Luke N., additional, Luo, Ming, additional, Guo, Ai-zhen, additional, Yang, Shan-shan, additional, Gu, Jing, additional, Turman, Breanna J., additional, Gao, Yun-rong, additional, Li, Dong-fang, additional, Cui, Zong-qiang, additional, Zhang, Zhi-ping, additional, Bi, Li-jun, additional, Baughn, Anthony D., additional, Zhang, Xian-En, additional, and Deng, Jiao-Yu, additional

Published
2014
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43. Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria.

Author

Ojha, Anil K, Baughn, Anthony D, Sambandan, Dhinakaran, Hsu, Tsungda, Trivelli, Xavier, Guerardel, Yann, Alahari, Anuradha, Kremer, Laurent, Jacobs, William R, Hatfull, Graham F, Ojha, Anil K, Baughn, Anthony D, Sambandan, Dhinakaran, Hsu, Tsungda, Trivelli, Xavier, Guerardel, Yann, Alahari, Anuradha, Kremer, Laurent, Jacobs, William R, and Hatfull, Graham F

Abstract

Successful treatment of human tuberculosis requires 6-9 months' therapy with multiple antibiotics. Incomplete clearance of tubercle bacilli frequently results in disease relapse, presumably as a result of reactivation of persistent drug-tolerant Mycobacterium tuberculosis cells, although the nature and location of these persisters are not known. In other pathogens, antibiotic tolerance is often associated with the formation of biofilms--organized communities of surface-attached cells--but physiologically and genetically defined M. tuberculosis biofilms have not been described. Here, we show that M. tuberculosis forms biofilms with specific environmental and genetic requirements distinct from those for planktonic growth, which contain an extracellular matrix rich in free mycolic acids, and harbour an important drug-tolerant population that persist despite exposure to high levels of antibiotics.

Published
2008

50. Mycobacterium tuberculosisFolate Metabolism and the Mechanistic Basis for para-Aminosalicylic Acid Susceptibility and Resistance

Author

Minato, Yusuke, Thiede, Joshua M., Kordus, Shannon Lynn, McKlveen, Edward J., Turman, Breanna J., and Baughn, Anthony D.

Abstract

ABSTRACTpara-Aminosalicylic acid (PAS) entered clinical use in 1946 as the second exclusive drug for the treatment of tuberculosis (TB). While PAS was initially a first-line TB drug, the introduction of more potent antitubercular agents relegated PAS to the second-line tier of agents used for the treatment of drug-resistant Mycobacterium tuberculosisinfections. Despite the long history of PAS usage, an understanding of the molecular and biochemical mechanisms governing the susceptibility and resistance of M. tuberculosisto this drug has lagged behind that of most other TB drugs. Herein, we discuss previous studies that demonstrate PAS-mediated disruption of iron acquisition, as well as recent genetic, biochemical, and metabolomic studies that have revealed that PAS is a prodrug that ultimately corrupts one-carbon metabolism through inhibition of the formation of reduced folate species. We also discuss findings from laboratory and clinical isolates that link alterations in folate metabolism to PAS resistance. These advancements in our understanding of the basis of the susceptibility and resistance of M. tuberculosisto PAS will enable the development of novel strategies to revitalize this and other antimicrobial agents for use in the global effort to eradicate TB.

Published
2015
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