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Antibiotics That Inhibit Nucleic Acid Synthesis

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Chemistry of Antibiotics and Related Drugs

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Abstract

Antibiotics that inhibit the synthesis of nucleic acids including DNA and RNA are presented. Background biochemistry information on the structure of DNA, replication, and transcription is provided. Antibiotics discussed include DNA intercalators, topoisomerase inhibitors such as nalidixic acid and fluoroquinolones, and nitroheterocycles such as nitroimidazoles and nitrofurans, RNA synthesis inhibitors such as actinomycin D and rifamycins are also included. Mechanisms of action of these drugs and resistance development against them are discussed.

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References

  1. Wainwright M (2001) Acridine—a neglected antibacterial chromophore. J Antimicrob Chemother 47:1–13

    Article  CAS  PubMed  Google Scholar 

  2. Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E, Inouye M (1966) Frameshift mutations and the genetic code. Cold Spring Harb Symp Quant Biol 31:77–84

    Article  CAS  PubMed  Google Scholar 

  3. Denny WA, Turner PM, Atwell GJ, Rewcastle GW, Ferguson LR (1990) Structure-activity relationships for the mutagenic activity of tricyclic intercalating agents in Salmonella typhimurium. Mutat Res 232:233–241

    Article  CAS  PubMed  Google Scholar 

  4. Ferguson LR, Denny WA (2007) Genotoxicity of non-covalent interactions: DNA intercalators. Mutat Res 623:14–23

    Article  CAS  PubMed  Google Scholar 

  5. Stevenson P, Sones KR, Gicheru MM, Mwangi EK (1995) Comparison of isometamidium chloride and homidium bromide as prophylactic drugs for trypanosomiasis in cattle at Nguruman, Kenya. Acta Trop 59:77–84

    Article  CAS  PubMed  Google Scholar 

  6. Lesher GY, Forelich EJ, Gruett MD, Bailey JH, Brundage RP (1962) 1,8-naphthyridine derivatives, a new class of chemotherapeutic agents. J Med Chem 5:1063–1065

    Article  CAS  Google Scholar 

  7. King DE, Malone R, Lilley SH (2000) New classification and update on the quinolone antibiotics. Am Fam Physician 61:2741–2748

    CAS  PubMed  Google Scholar 

  8. Emmerson AM, Jones AM (2003) The quinolones: decades of development and use. J Antimicrob Chemother 51(Suppl 1):13–20

    Article  CAS  PubMed  Google Scholar 

  9. Galante D, Pennucci C, Esposito S, Barba D (1985) Comparative in vitro activity of ciprofloxacin and five other quinoline derivatives against gram-negative isolates. Drugs Exp Clin Res 11:331–334

    CAS  PubMed  Google Scholar 

  10. Smith SM, Eng RH (1985) Activity of ciprofloxacin against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 27:688–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ridgway GL, Mumtaz G, Gabriel FG, Oriel JD (1984) The activity of ciprofloxacin and other 4-quinolones against Chlamydia trachomatis and Mycoplasmas in vitro. Eur J Clin Microbiol 3:344–346

    Article  CAS  PubMed  Google Scholar 

  12. Lawrence LE, Wu P, Fan L, Gouvei KE, Card A, Casperson M, Denbleyker K, Barrett JF (2001) The inhibition and selectivity of bacterial topoisomerases by BMS-284756 and its analogues. J Antimicrob Chemother 48:195–201

    Article  CAS  PubMed  Google Scholar 

  13. Collin F, Karkare S, Maxwell A (2011) Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 92:479–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Drlica K, Zhao X (1997) DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377–392

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hoshino K, Kitamura A, Morrissey I, Sato K, Kato J, Ikeda H (1994) Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition. Antimicrob Agents Chemother 38:2623–2627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Khodursky AB, Zechiedrich EL, Cozzarelli NR (1995) Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci U S A 92:11801–11805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hawkey PM (2003) Mechanisms of quinolone action and microbial response. J Antimicrob Chemother 51(SI):29–35

    Article  CAS  PubMed  Google Scholar 

  18. Chen CR, Malik M, Snyder M, Drlica K (1996) DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage. J Mol Biol 258:627–637

    Article  CAS  PubMed  Google Scholar 

  19. Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, Collins JJ (2007) A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130:797–810

    Article  CAS  PubMed  Google Scholar 

  20. Dwyer D, Kohanski M, Hayete B, Collins J (2007) Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol Syst Biol 3:91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Drlica K, Hiasa H, Kerns R, Malik M, Mustaev A, Zhao X (2009) Quinolones: action and resistance updated. Curr Top Med Chem 9:981–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Walsh TJ, Standiford HC, Reboli AC, John JF, Mulligan ME, Ribner BS, Montgomerie JZ, Goetz MB, Mayhall CG, Rimland D, Stevens DA, Hansen SL, Gerard GC, Ragual RJ (1993) Randomized double-blinded trial of Rifampin with either Novobiocin or trimethoprimsulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: prevention of antimicrobial resistance and effect of host factors on outcome. Antimicrob Agents Chemother 37:1334–1342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nikaido H (1998) Antibiotic resistance caused by gram negative multidrug efflux pumps. Clin Infect Dis 27(suppl 1):S32–S41

    Article  CAS  PubMed  Google Scholar 

  24. Li XZ, Livermore DM, Nikaido H (1994) Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin. Antimicrob Agents Chemother 38:1732–1741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ruiz J (2003) Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother 51:1109–1117

    Article  CAS  PubMed  Google Scholar 

  26. Ito H, Yoshida H, Bogaki-Shonai M, Niga T, Haytori H, Nakamura S (1994) Quinolone resistance mutations in the DNA Gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob Agents Chemother 38:2014–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stevenson JE, Gray K, Barrett TJ, Medalla F, Chilller TM, Angulo FJ (2007) Increase in nalidixic acid resistance among non-Typhi Salmonella enterica isolates in the United States from 1996 to 2003. Antimicrob Agents Chemother 51:195–197

    Article  CAS  PubMed  Google Scholar 

  28. Maruri F, Sterling TR, Kaiga AW, Blackman A, van der Heijden YF, Mayer C, Cambau E, Aubry A (2012) A systematic review of gyrase mutations associated with fluoroquinolone resistant Mycobacterium tuberculosis and a proposed gyrase numbering system. J Antimicrob Chemother 67:819–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Valdezate S, Vindel A, Baquero F, Cantón R (1999) Comparative in vitro activity of quinolones against Stenotrophomonas maltophilia. Eur J Clin Microbiol Infect Dis 18:908–911

    Article  CAS  PubMed  Google Scholar 

  30. Gu Y, Xu X, Lin L, Ren X, Cui X, Hou X, Cui S (2013) Functional characterization of quinolone-resistant mechanisms in a lab-selected Salmonella enterica typhimurium mutant. Microb Drug Resist 19:15–20

    Article  CAS  PubMed  Google Scholar 

  31. Martinez-Martinez L, Pascual A, Jacoby GA (1998) Quinolone resistance from a transferable plasmid. Lancet 351:797–799

    Article  CAS  PubMed  Google Scholar 

  32. Tran JH, Jacoby GA (2002) Mechanism of plasmid mediated quinolone resistance. Proc Natl Acad Sci U S A 99:5638–5642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jacoby GA, Chow N, Waites KB (2003) Prevalence of plasmid-mediated quinolone resistance. Antimicrob Agents Chemother 47:559–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pommier Y, Leo E, Zhang HL, Marchand C (2010) DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol 17:421–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nitiss JL (2009) Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer 9:338–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Maeda K, Osato T, Umezawa H (1953) A new antibiotic, azomycin. J Antibiot (Tokyo) 6:182

    CAS  Google Scholar 

  37. Shinn DLS (1962) Metronidazole in acute ulcerative gingivitis. Lancet 279:1191

    Article  Google Scholar 

  38. Edwards DI (1980) Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs. Br J Vener Dis 56:285–290

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ings RMJ, McFadzean JA, Ormerod WE (1974) The mode of action of metronidazole in Trichomonas vaginalis and other micro-organisms. Biochem Pharmacol 23:1421–1429

    Article  CAS  PubMed  Google Scholar 

  40. Muller M (1983) Mode of action of metronidazole on anaerobic bacteria and protozoa. Surgery 93:165–171

    CAS  PubMed  Google Scholar 

  41. Samuelson J (1999) Why metronidazole is active against both bacteria and parasites. Antimicrob Agents Chemother 43:1533–1541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vidakovic M, Crossnoe CR, Neidre C, Kim K, Krause KL, Germanas JP (2003) Reactivity of reduced [2Fe-2S] ferredoxins parallels host susceptibility to nitroimidazoles. Antimicrob Agents Chemother 47:302–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Miyachi Y, Imamura S, Niwa Y (1986) Anti-oxidant action of metronidazole: a possible mechanism of action in rosacea. Br J Dermatol 114:231–234

    Article  CAS  PubMed  Google Scholar 

  44. Akamatsu H, Oguchi M, Nishijima S, Asada Y, Takahashi M, Ushijima T, Niwa Y (1990) The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne. Arch Dermatol Res 282:449–454

    Article  CAS  PubMed  Google Scholar 

  45. Chaudhry R, Mathur P, Dhawan B, Kumar L (2001) Emergence of metronidazole-resistant bacteroides fragilis, India. Emerg Infect Dis 7:485–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Goodwin A, Kersulyte D, Sisson G, Veldhuyzen van Zanten SJ, Berg DE, Hoffman PS (1998) Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol Microbiol 28:383–393

    Article  CAS  PubMed  Google Scholar 

  47. McCalla DR, Reuvers A, Kaiser C (1971) Breakage of bacterial DNA by nitrofuran derivatives. Cancer Res 31:2184–2188

    CAS  PubMed  Google Scholar 

  48. Munoz-Davila MJ (2014) Role of old antibiotics in the era of antibiotic resistance. Highlighted nitrofurantoin for the treatment of lower urinary tract infections. Antibiotics 3:39–48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Sandegren L, Lindqvist A, Kahlmeter G, Andersson DI (2008) Nitrofurantoin resistance mechanism and fitness cost in Escherichia coli. J Antimicrob Chemother 62:495–503

    Article  CAS  PubMed  Google Scholar 

  50. McOsker CC, Fitzpatrick PM (1994) Nitrofurantoin: mechanism of action and implications for resistance development in common uropathogens. J Antimicrob Chemother 33(Suppl A):23–30

    Article  CAS  PubMed  Google Scholar 

  51. Whiteway J, Koziarz P, Veall J, Sandhu N, Kumar P, Hoecher B, Lambert IB (1998) Oxygen insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli. J Bacteriol 180:5529–5539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bala S, Khanna R, Dadhwal M, Prabagaran SR, Shivaji S, Cullum J, Lal R (2004) Reclassification of Amycolatopsis mediterranei DSM 46095 as Amycolatopsis rifamycinica sp. nov. Int J Syst Evol Microbiol 54:1145–1149

    Article  CAS  PubMed  Google Scholar 

  53. Kim TK, Hewavitharana AK, Shaw PN, Fuerst JA (2006) Discovery of a new source of rifamycin antibiotics in marine sponge actinobacteria by phylogenetic prediction. Appl Environ Microbiol 72:2118–2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA (2001) Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104:901–912

    Article  CAS  PubMed  Google Scholar 

  55. Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, Matter L, Schopfer K, Bodmer T (1993) Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 341:647–650

    Article  CAS  PubMed  Google Scholar 

  56. Chaisson RE (2003) Treatment of chronic infections with rifamycins: is resistance likely to follow? Antimicrob Agents Chemother 47:3037–3039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sobell HM (1985) Actinomycin and DNA transcription. Proc Natl Acad Sci U S A 82:5328–5331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot 62:5–16

    Article  CAS  Google Scholar 

  59. Artsimovitch I, Seddon J, Sears P (2012) Fidaxomicin is an inhibitor of the initiation of bacterial RNA synthesis. Clin Infect Dis 55(S2):S127–S131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Babakhani F, Seddon J, Sears P (2014) Comparative microbiological studies of transcription inhibitors fidaxomicin and the rifamycins in Clostridium difficile. Antimicrob Agents Chemother 58:2934–2937

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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  1. Department of Chemistry and Biochemistry, Long Island University, Brooklyn, NY, USA

    Mrinal K. Bhattacharjee

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  1. Mrinal K. Bhattacharjee
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Bhattacharjee, M.K. (2022). Antibiotics That Inhibit Nucleic Acid Synthesis. In: Chemistry of Antibiotics and Related Drugs. Springer, Cham. https://doi.org/10.1007/978-3-031-07582-7_5

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