リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Impact of QnrB19, a pentapeptide repeat protein mimicking double stranded DNA, on the quinolone resistance in Salmonella Typhimurium.」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Impact of QnrB19, a pentapeptide repeat protein mimicking double stranded DNA, on the quinolone resistance in Salmonella Typhimurium.

Ruttana, PACHANON 北海道大学

2020.09.25

概要

Fluoroquinolones have been used for the drugs of choice to treat non-typhoidal Salmonella (NTS) infection in humans and animals. However, plasmid-mediated quinolone resistance (PMQR) mechanism has emerged in Enterobacteriaceae. Plasmid-encoded quinolone resistance protein Qnr is an important factor among PMQR in bacterial resistance to quinolones. This protein interacts with DNA gyrase and reduces susceptibility to quinolones.

　However, as there are limited information of the predominant Qnr types in Salmonella isolates, I investigated the prevalence of Qnr in 692 reports published from 2008 to 2017 and found that 4,459 Enterobacteriaceae isolates had Qnrs (1,917 QnrB, 1,545 QnrS, 498 QnrA, 459 QnrD, 27 QnrVC, 12 QnrC and 1 QnrE). And QnrB19 was found in the highest number of isolates among Qnr reported in Salmonella isolates.

　In Chapter I, in vitro assays for wild type S. Typhimurium DNA gyrases, QnrB19 and quinolones were performed. The IC50s of norfloxacin and ciprofloxacin against DNA gyrases were increased around 3-fold by the addition of QnrB19 and the results exhibited that the contribution of QnrB19 did not associate with the difference between R1 group of these two quinolones. The IC50 of nalidixic acid was 59- and 110-folds higher than norfloxacin and of ciprofloxacin in the absence of QnrB19, respectively, and this was similar to the that in the presence of 18 nM QnrB19. These results showed that the fluorine at R6 and/or piperazine at R7 and/or hydrogen at R8 group might associate with the ability of QnrB19 to increase IC50s. QnrB19 was shown for the first time in vitro to have ability to grant non-classical quinolone resistance to S. Typhimurium DNA gyrase in connection with the structure at R6 and/or R7 and/or R8.

　In Chapter II, I identified the activity of novel fluoroquinolones with the potentiality attributed by unique R1 group, 6-amino-3,5-difluoropyridine-2-yl, by in vitro assay. I compared IC50 of WQ-3810, WQ-3334 and WQ-4065 with specific features of quinolones at positions R1, R6, R7 or R8. WQ-3810 and WQ-3334 (6-amino-3,5-difluoropyridine-2-yl at the R1 group) showed stronger inhibitory activity against S. Typhimurium DNA gyrases with a lower IC50s than WQ-4065 (6-ethylamino-3,5-difluoropyridine-2-yl at the R1). Moreover, WQ-3810 and WQ-3334 showed greater inhibitory activity against S. Typhimurium DNA gyrases even in the presence of QnrB19. The results suggested that novel fluoroquinolones, WQ-3810 and WQ-3334 could be the good candidate drug for wild type Salmonella and Salmonella carrying QnrB19.

　Comparison of conventional quinolones (nalidixic acid, norfloxacin and ciprofloxacin) in Chapter I and novel fluoroquinolones (WQ-3810, WQ-3334 and WQ-4065) in Chapter II showed that 6-amino-3,5-difluoropyridine-2-yl group at the R1 in WQ-3810 and WQ-3334 added a strong inhibitory activity against S. Typhimurium DNA gyrases to quinolones with very low IC50. IC50s of WQ-3810 and WQ-3334 were greatly increased in the presence of QnrB19, however, similar to those of ciprofloxacin and norfloxacin. Structural at R1 may cause the different impact by QnrB19 on the inhibitory activities of quinolones against DNA gyrase. The knowledge obtained in my study can be applied to design new compounds against bacteria carrying QnrB19 or other pentapeptide repeat proteins.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

[1] Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ et al. Typhoid fever. N Engl J Med. 347:1770-82, 2002.

[2] Parry CM, Basnyat B, Crump JA. The management of antimicrobial-resistant enteric fever. Expert Rev Anti Infect Ther. 11:1259-61, 2013.

[3] Jessica MH, Beau BB. CDC. Salmonellosis (Nontyphoidal) - Chapter 4, https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious- diseases/salmonellosis-nontyphoidal; 2019 [accessed 21 November 2019].

[4] WHO. Salmonella (non-typhoidal), https://www.who.int/news-room/fact- sheets/detail/salmonella-(non-typhoidal); 2019 [accessed 3 October 2019].

[5] Gal-Mor O, Boyle EC, Grassl GA. Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. Front Microbiol. 5:1–10, 2014.

[6] Sakugawa Shinohara NK, Bezerra de Barros V, Castro Jimenez SM, de Castro Lima Machado E, Fireman Dutra RA, de Lima JL. Salmonella spp., importante agente patogênico veiculado em alimen-tos. Ciênc Saúde Coletiva. 13:1675–83, 2008.

[7] Berger CN, Sodha SV, Shaw RK, Griffin PM, Pink D, Hand P, Frankel G. Fresh fruit and vegetables as vehicles for the transmission of human pathogens: fresh produce as vehicles for transmission of human pathogens. Environ Microbiol. 12:2385–97, 2010.

[8] World Health Organization, Foodborne Disease Burden Epidemiology Reference Group. WHO estimates of the global burden of food-borne diseases. World Health Organization, Geneva, Switzerland, 2015.

[9] Uzzau S, Brown DJ, Wallis T, Rubino S, Leori G, Bernard S, et al. Host-adapted serotypes of Salmonella enterica. Epidemiol Infect. 125:229-55, 2000.

[10] Ao TT, Feasey NA, Gordon MA, Keddy KH, Angulo FJ et al. Global burden of invasive nontyphoidal Salmonella disease, 2010. Emerg Infect Dis. 21:941–9, 2015.

[11] Stanaway J, Parisi A, Sarkar K, Blacker B, Reiner R et al. The global burden of non- typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 19: 1312-24, 2019.

[12] Whistler T, Sapchookul P, McCormick D, Sangwichian O, Jorakate P et al. Epidemiology and antimicrobial resistane of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014. PLoS Negl Trop Dis. 12(8):e0006718, 2018.

[13] Uche IV, MacLennan CA, Saul A. A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014). PLoS Negl Trop Dis. 11(1):e0005118, 2017.

[14] Crump JA, Heyderman RS. A Perspective on Invasive Salmonella Disease in Africa. Clin Infect Dis. 61(Suppl 4):S235-40, 2015

[15] Morpeth SC, Ramadhani HO, Crump JA. Invasive non-Typhi Salmonella disease in Africa. Clin Infect Dis. 49(4):606-11, 2009.

[16] Bula-Rudas FJ, Rathore MH, Maraqa NF. Salmonella Infections in Childhood. Adv in Pediatr. 62(1):29-58, 2015.

[17] Garcia C, Hinostroza N, Astocondor L, Ochoa T, Jacobs J, For The Salmoiber Cyted Network. Characterization of ESBL-Producing Salmonella enterica Serovar Infantis Infection in Humans, Lima, Peru. Am J Trop Med Hyg. 101:746-8, 2019.

[18] Li Y, Xie X, Xu X et al. Nontyphoidal Salmonella infection in children with acute gastroenteritis: Prevalence, serotypes, and antimicrobial resistance in Shanghai, China. Foodborne Pathog. Dis. 11:200-6, 2014.

[19] Crump JA, Medalla FM, Joyce KW et al. Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National antimicrobial resistance monitoring system, 1996 to 2007. Antimicrob Agents Chemother. 55: 1148-54, 2011.

[20] Lee H-Y, Su L-H, Tsai M-H, Kim S-W, Chang H-H, Jung S-I, et al. High rate of reduced susceptibility to ciprofloxacin and ceftriaxone among nontyphoid Salmonella clinical isolates in Asia. Antimicrob Agents Chemother. 53(6):2696-9, 2009.

[21] Cuypers WL, Jacobs J, Wong V, Klemm EJ, Deborggraeve S, Van Puyvelde S. Fluoroquinolone resistance in Salmonella: Insights by wholegenome sequencing. Microb Genom. 4(7), 2018.

[22] Hooper DC. Bacterial Topoisomerases, Anti-Topoisomerases, and Anti-Topoisomerase Resistance. Clin Infect Dis. 27 Suppl 1:S54-63, 1998.

[23] Klostermeier D. Why two? On the role of (A-) symmetry in negative supercoiling of DNA by gyrase. Int. J. Mol. Sci. 19(5) pp:1489, 2018.

[24] Deweese JE, Osheroff N. The use of divalent metal ions by type II topoisomerases. Metallomics. 2(7):450-9, 2010.

[25] Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry. 18;53(10):1565-74, 2014.

[26] Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis. 6(10):629-40, 2006.

[27] Correia S, Hebraud M, Chafsey I, Chambon C, Viala D et al. Impacts of experimentally induced and clinically acquired quinolone resistance on the membrane and intracellular subproteomes of Salmonella Typhimurium DT104B. J Proteomics. 145:46-59, 2016.

[28] Vetting MW, Hegde SS, Fajardo JE, Fiser A, Roderick SL, Takiff HE, Blanchard JS. Pentapeptide repeat proteins. Biochem. 45(1):1-10, 2006.

[29] Tran JH, Jacoby GA. Mechanism of plasmid-mediated quinolone resistance. Proc Natl Acad Sci U S A. 99(8):5638-42, 2002.

[30] Tran JH, Jacoby GA, Hooper DC. Interaction of the plasmid-encoded quinolone resistance protein Qnr with Escherichia coli DNA gyrase. Antimicrob Agents Chemother. 49(1):118-25, 2005a.

[31] Shah S, Heddle JG. Squaring up to DNA: pentapeptide repeat proteins and DNA mimicry. Appl Microbiol Biotechnol. 98:9545-60, 2014.

[32] Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature. 466(7309):935-40, 2010a

[33] Xiong X, Bromley EH, Oelschlaeger P, Woolfson DN, Spencer J. Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a gram-negative bacterium. Nucleic Acids Res. 39(9):3917-27, 2011.

[34] Jacoby G, Cattoir V, Hooper D, Martínez-Martínez L, Nordmann P, Pascual A, et al. qnr Gene Nomenclature. Antimicrob Agents Chemother. 52(7):2297-9, 2008.

[35] Wang M, Jacoby GA, Mills DM, Hooper DC. SOS regulation of qnrB expression. Antimicrob Agents Chemother. 53(2):821-3, 2009.

[36] Da Re S, Garnier F, Guérin E, Campoy S, Denis F, Ploy MC. The SOS response promotes qnrB quinolone-resistance determinant expression. EMBO Rep. 10(8):929-33, 2009.

[37] Vetting M, Hegde S, Wang M, Jacoby G, Hooper D, Blanchard J. Structure of QnrB1, a plasmid-mediated fluoroquinolone resistance facter. J Biol Chem. 15;286(28)25265-73, 2011.

[38] Jacoby GA, Walsh KE, Mills DM, Walker VJ, Oh H, Robicsek A, et al. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother. 50(4):1178-82, 2006.

[39] Mérens A, Matrat S, Aubry A, Lascols C, Jarlier V, Soussy CJ, et al. The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the Ternary gyrase-DNA-quinolone complex. J Bacteriol. 191(5):1587-94, 2009.

[40] Tavío MM, Jacoby GA, Hooper DC. QnrS1 structure-activity relationships. J Antimicrob Chemother. 69(8):2102-9, 2014.

[41] Kazamori D, Aoi H, Sugimoto K, Ueshima T, Amano H, Itoh K, et al. In vitro activity of WQ-3810, a novel fluoroquinolone, against multidrug-resistant and fluoroquinolone- resistant pathogens. Int J Antimicrob Agents. 44:443-9, 2014.

[42] Koide K, Kongsoi S, Nakajima C, Suzuki Y. WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium. Biosci Biotechnol Biochem. 12:2249-56, 2019.

[43] Ouchi Y, Mukai T, Koide K, Yamaguchi T, Park JH, Kim H, et al. WQ-3810: A new fluoroquinolone witha high potential against fluoroquinolone-resistant Mycobacterium tuberculosis. Tuberculosis (Edinb). 120:101891, 2020.

[44] Park JH, Yamaguchi T, Ouchi Y, Kentaro K, Mori S, Kim H, et al. WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae. J Infect Chemother. 26(4):335-42, 2020.

[45] Itoh K, Kuramoto Y, Amano H, et al. Discovery of WQ-3810: design, synthesis, and evaluation of 7-(3-alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents. Eur J Med Chem. 103:354-60, 2015.

[46] Tsumoto K, Umetsu M, Kumagai I, Ejima D, Philo JS, Arakawa T. Role of arginine in protein refolding, solubilization, and purification. Biotechnol Prog. 20(5):1301-8, 2004.

[47] Kongsoi S, Yokoyama K, Suprasert A, Utrarachkij F, Nakajima C, Suthienkul O, et al. Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones. Drug Test Anal. 7:714-20, 2015.

[48] Matrat S, Petrella S, Cambau E, Sougakoff W, Jarlier V, Aubry A. Expression and purification of an active form of the Mycobacterium leprae DNA gyrase and its inhibition by quinolones. Antimicrob Agents Chemother. 51(5):1643-8, 2007.

[49] Kim H, Nakajima C, Yokoyama K, Rahim Z, Kim YU, Oguri H, et al. Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance. Antimicrob Agents Chemother. 55(8):3661-7, 2011.

[50] Yokoyama K, Kim H, Mukai T, Matsuoka M, Nakajima C, Suzuki Y. Amino acid substitutions at position 95 in GyrA can add fluoroquinolone resistance to Mycobacterium leprae. Antimicrob Agents Chemother. 56(2):697-702, 2012.

[51] Hegde SS, Vetting MW, Mitchenall LA, Maxwell A, Blanchard JS. Structural and Biochemical Analysis of the Pentapeptide Repeat Protein EfsQnr, a Potent DNA Gyrase Inhibitor. Antimicrob Agents Chemother. 55(1):110-7, 2011.

[52] Arsène S, Leclercq R. Role of a qnr-Like Gene in the Intrinsic Resistance of Enterococcus faecalis to Fluoroquinolones. Antimicrob Agents Chemother. 51(9):3254-8, 2007.

[53] Peterson LR. Quinolone molecular structure-activity relationships: what we have learned about improving antimicrobial activity. Clin Infect Dis. 15;33 Suppl 3:S180-6, 2001.

[54] Pachanon R, Koide K, Kongsoi S, Nakajima C, Kapalamula TF, Suthienkul O, and Suzuki, Y, 2020. Interaction of the plasmid-encoded quinolone resistance protein QnrB19 with Salmonella Typhimurium DNA gyrase. J Infect Chemother, in press.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る