New Strategies of Antibiotic Development

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Since discovery of wonder drug penicillin by Sir Alexander Flaming, many antibiotics have previously been discovered while many others are in process of development and clinical evaluation .However a newly discovered  antibiotics has a short valuable life time since its long term clinical use results into development of resistance in target pathogens rendering the antibiotics ineffective against its target(s).Therefore for antibiotics to remain in demand for clinical use. So pains are needed towards search for antibiotics with distinctive scaffolds and/or  novel mechanism of action besides useful shelf and clinical life time. Some of  the hopeful strategies to accomplish this target are (a)Finding new antibiotics from old microbial sources(b)Finding new microbial sources of antibiotics (c)Accessing greater bacterial diversity thus exploiting known/unknown microbial sources in large numbers.(d)Adapting novel culture techniques. The paper presented here draws focus on some valuable clues in finding new antibiotics
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Antibiotics; Resistance; New Strategies; Development

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Walsh Christopher (2003) Perspective-Where will new antibiotics come from?. Nature publishing group 1: 65-70.

Bax RP, Anderson R, Crew J, Fletcher P, Johnson T, Kaplan E, et al. (1998) Antibiotic resistance—what can we do. Nat Med 4:545–546.

Coates A R M and Hu Y(2007).Novel approaches to developing new antibiotics for bacterial infections Br J Pharmacol 152(8): 1147–1154.

Bax RP, Mullan N (1999) Response of the pharmaceutical industry to antimicrobial resistance. Balliere Clin Infect Dis 5:289–304.

Coates A, Hu Y, Bax R, Page C. The future challenges facing the development of new antimicrobial drugs. Nat Rev Drug Discov. 2002;1:895–910.

Fleming A. (1929) On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol. 10:226.

Abraham EP, Cephalosporins 1945–86 The Cephalosporins (1987) Adis Press: Auckland; 1–14.14In: Williams, JD (ed).

Pelaez F (2006) The historical delivery of antibiotics from microbial natural products—can history repeat. Biochem Pharmacol. 71:981–990.

Rolinson GN, Geddes AM (2007) The 50th anniversary of the discovery of 6-aminopenicillanic acid (6-APA) Int J Antimicrob Agents. 29:3–8.

Zhanel GG, Homenuik K, Nichol K, Noreddin A, Vercaigne L, Embil J (2004) The glycylcyclines: a comparative review with the tetracyclines. Drugs. 64:63–88.

Zuckerman JM(2004) Macrolides and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin North Am. 18:621–649.

Clardy jon, fischbach A Michael ,Walse T Christopher (2006) New antibiotics from bacterial natural product,Nature biotechnology 24(12) : 1541-1550

Fernandez P(2006) Antibacterial discovery and development-the failure of success. Nat Biotechnol. 24:1497–1503.

Barbachyn MR, Ford CW (2003) Structure–activity relationships leading to linezolid. Angew Chem Int Ed Engl 42:2010–2023.

Finch R. (2006) Gram-positive infections: lessons learnt and novel solutions. Clin Microbiol Infect. 12 Suppl 8:3–8.

Kern WV. Daptomycin (2006) first in a new class of antibiotics for complicated skin and soft-tissue infections. Int J Clin Pract. 60:370–378.

Tally FP, DeBruin MF(2000) development of daptomycin for gram-positive infections. J Antimicrob.chemother 46 :523-526.

Rolinson GN. The history and background of Augmentin. S Afr Med J. 1982;28:3A–4A.

Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE (2004) Jr Trends in antimicrobial drug development: implications for the future. Clin Infect Dis. 38:1279–1286.

Coates AR, Hu Y (2006) New strategies for antibacterial drug design: targeting non-multiplying latent bacteria. Drugs R D 7:133–151.

Reynolds R, Potz N, Colman M, Williams A, Livermore D, MacGowan A., BSAC Extended Working Party on Bacteraemia Resistance Surveillance Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001–2002: the BSAC Bacteraemia Resistance Surveillance Programme. J Antimicrob Chemother. 2004;53:1018–1032.

Karchmer AW(2004) Increased antibiotic resistance in respiratory tract pathogens: PROTEKT US—an update. Clin Infect Dis. 39 suppl 3:S142–S150.

Paterson DL(2006) The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clin Infect Dis. 43 Suppl 2:S43–S48.

Livermore D.M.(2004)The need for new antibiotics. Clinical Microbiol infect 10 (Suppl. 4): 1–9

CJ Thomson, E Power , H Ruebsamen-Waigmann, H Labischinski (2004) Antibacterial research and development in the 21(st) Century--an industry perspective of the challenges.Curr Opin Microbiol. 7(5):445-50.

Projan SJ, Shlaes DM(2004) Antibacterial drug discovery: is it all downhill from here. Clin Microbiol Infect. 10:18–22.

Zurenko GE, Ford CW, Hutchinson DK, Brickner SJ, Barbachyn MR (1997) Oxazolidinone antibacterial agents: development of the clinical candidates eperezolid and linezolid. Expert Opin Investig Drugs. 6:151–158.

Ford CW, Zurenko GE, Barbachyn MR (2001) The discovery of linezolid, the first oxazolidinone antibacterial agent. Curr Drug Targets Infect Disord. 1:181–199.

Fox JL. (2006)The business of developing antibacterials. Nat Biotechnol. 24:1521–1528.

Metlay JP, Powers JH, Dudley MN, Christiansen K, Finch RG (2006) Antimicrobial drug resistance, regulation, and research. Emerg Infect Dis. 12:183–190.

Bradley JS, Guidos R, Baragona S, Bartlett JG, Rubinstein E, Zhanel GG (2007) Anti-infective research and development—problems, challenges, and solutions. Lancet Infect Dis 7:68–78.

Norrby SR, Nord CE, Finch R (2005) European Society of Clinical Microbiology and Infectious Diseases Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancet Infect Dis. 5:115–119.

Sheridan C(2006). Antibiotics au naturel. Nat Biotechnol. 24:1494–1496.

Wang J, Soisson SM, Young K, Shoop W, Kodal S, Galgoci A (2006) Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature. 441:358–361.

Lewis K, Ausubel FM(2006)Prospects for plant-derived antibacterials. Nat Biotechnol. 24:1504–1507.

Watve M.G. tickoo,R.,jog,M.M. ,Bhole,B.D. (2001)How many antibiotics produced by the genus streptomyces ? Arch. Microbio. 176: 386-390.

Monaghan RL, Barrett JF(2006) Antibacterial drug discovery—then, now and the genomics future. Biochem Pharmacol. 71:901–909.

Haney SA, Alkane LE, Dunman PM, Murphy E, Projan SJ ,(2002) Genomics in anti-infective drug discovery-getting to endgame. Curr Pharmaceut Des. 8:1099–1118.

McDevitt D, Rosenberg M(2001). Exploiting genomics to discover new antibiotics. Trends Microbiol. 9:611–617.

Dougherty TJ, Miller PF (2006) Microbial genomics and drug discovery: exploring innovative routes of drug discovery in the postgenomic era. IDrugs 9:420–422.

Freiberg C(2005) Brotz-Oesterhelt H. Functional genomics in antibacterial drug discovery. Drug Discov Today 10:927–935.

Sakharkar KR, Sakharkar MK, Chow VT (2004) A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol. 4:355–360.

Arcus VL, Lott JS, Johnston JM, Baker EN(2006) The potential impact of structural genomics on tuberculosis drug discovery. Drug Discov Today 11:28–34.

Black MT, Hodgson J (2005) Novel target sites in bacteria for overcoming antibiotic resistance. Adv Drug Deliv Rev 57:1528–1538.

Fournier PE, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L (2006) Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet. 2:e7.

Jagusztyn-Krynicka Elzbieta k., wyszynnska agnieskzka(2008) The decline of Antibiotic Era-New Approaches for Antibacterial drug discovery. polish journal of microbiology 57(2):91-98

Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL (2007) Drugs for bad bugs: confronting the challenges of antibacterial drug discovery. Nat Rev Drug Discov. 6:29–40.

McAlpine, J. B. (2005)Microbial genomics as a guide to drug discovery and structure elucidation: ECO-02301, a novel antifungal agent, as an example. J. Nat. Prod. 68:493–496.

Banskota, A. H. et al (2006) Genomic analyses lead to novel secondary metabolites. Part 3. ECO-0501, a novel antibacterial of a new class. J. Antibiot. 59:533–542.

Gross, H (2007) The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters. Chem. Biol. 14:53–63.

Diaz-Torres ML, Villedieu A, Hunt N, McNab R, Spratt DA, Allan E (2006) Determining the antibiotic resistance potential of the indigenous oralmicrobiota of humans using a metagenomic approach. FEMS Microbiol Lett 258:257–262.

Garcia MH, Ivanova N, Kunin V, Warnecke F, Barry KW, McHardy AC (2006) Metagenomic analysis of two enhanced biological phosphorus removal (EBPR) sludge communities. Nat Biotechnol. 24:1263–1269.

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031.

Jones BV, Marchesi JR(2007) Transposon-aided capture (TRACA) of plasmids resident in the human gut mobile metagenome. Nat Methods 4:55–61.

Ono A, Miyazaki R, Sota M, Ohtsubo Y, Nagata Y, Tsuda M (2007) Isolation and characterization of naphthalene-catabolic genes and plasmids from oil-contaminated soil by using two cultivation-independent approaches. Appl Microbiol Biotechnol. 74:501–510.

Singh S. B., Phillips, J. W..Wang, J.(2007) Highly sensitive target-based whole-cell antibacterial discovery strategy by antisense RNA silencing. Curr. Opin. Drug Discov. Devel. 10:160–166.

Donadio S, Maffioli S, Monciardini P, Sosio M,Jabes D (2010) Antibiotic discovery in the twenty-first century: current trends and future perspectives. The Journal of Antibiotics 1–8.

Borysowski J, Weber-Dabrowska B, Gorski A. Bacteriophage endolysins as a novel class of antibacterial agents. Exp Biol Med (Maywood) 2006;231:366–377.

Hendrix RW (2002) Bacteriophages: evolution of the majority. Theor Popul Biol 61:471–480.

Sulakvelidze A, Alavidze Z, Morris JG(2001). Bacteriophage therapy. Antimicrob Agents Chemother. 45:649–659.

Liu J, Dehbi M, Moeck G, Arhin F, Bauda P, Bergeron D (2004) Antimicrobial drug discovery through bacteriophage genomics. Nat Biotechnol. 22:185–191.

Skurnik M. and E. Strauch, 2006. Phage therapy: facts and fiction. In. J. Med. Microbiol. 296: 5-14.

Withey S, Cartmell E, Avery LM, Stephenson T (2005) Bacteriophages—potential for application in wastewater treatment processes. Sci Total Environ. 339:1–18.

Nakai T, Park SC (2002) Bacteriophage therapy of infectious diseases in aquaculture. Res Microbiol.,153:13–18.

Huff WE, Huff GR, Rath NC, Balog JM, Donoghue AM(2003) Bacteriophage treatment of a severe Escherichia coli respiratory infection in broiler chickens. Avian Dis. 47:1399–1405.

Doyle MP, Erickson MC (2006) Reducing the carriage of foodborne pathogens in livestock and poultry. Poult Sci. 85:960–973.

Sheng H, Knecht HJ, Kudva IT, Hovde CJ (2006) Application of bacteriophages to control intestinal Escherichia coli O157:H7 levels in ruminants. Appl Environ Microbiol. 72:5359–5366.

Dabrowska K, Switala-Jelen K, Opolski A, Weber-Dabrowska B, Gorski A(2005) Bacteriophage penetration in vertebrates. J Appl Microbiol 98:7–13.

Matsuda T, Freeman TA, Hilbert DW, Duff M, Fuortes M, Stapleton PP (2005)Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model. Surgery. 137:639–646.

Yacoby I, Shamis M, Bar H, Shabat D, Benhar I(2006) Targeting antibacterial agents by using drug-carrying filamentous bacteriophages. Antimicrob Agents Chemother.,50:2087–2097.

Fischetti VA, Nelson D, Schuch R(2006) Reinventing phage therapy: are the parts greater than the sum. Nat Biotechnol 24:1508–1511.

Nelson D, Loomis L, Fischetti VA(1997) Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme. Proc Natl Acad Sci USA 98:4107–4112.

Loeffler JM, Nelson D, Fischetti VA(2001) Rapid killing of Streptococcus pneumoniae with a bacteriophage cell wall hydrolase. Science. 294:2170–2172.

Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S (2004) Bacterial persistence as a phenotypic switch. Science 305:1622–1625.

Entenza JM, Loeffler JM, Grandgirard D, Fischetti VA, Moreillon P(2005) Therapeutic effects of bacteriophage Cpl-1 lysin against Streptococcus pneumoniae endocarditis in rats. Antimicrob Agents Chemother. 49:4789–4792.

Bernhardt TG, Wang IN, Struck DK, Young R(2001) A protein antibiotic in the phage Qbeta virion: diversity in lysis targets. Science 292:2326–2329.

Bugg TD, Lloyd AJ, Roper DI (2006) Phospho-MurNAc-pentapeptide translocase (MraY) as a target for antibacterial agents and antibacterial proteins. Infect Disord Drug Targets 6:85–106.

World Health Organisation. WHO global strategy for the containment of antimicrobial resistance. Available at : http:// Accessed on 24th October 2011.)

Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496–512.

Hu Y, Coates AR, Mitchison DA(2003) Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 47:653–657.

World Health Organisation. WHO 51.17 Emerging and other communicable diseases. Available at: docs/index/assoc/s16334e/s16334e.pdf. Accessed on 24th October 2011.

World Health Organisation. WHO efforts to contain antimicrobial resistance. Available at: en/. Accessed on 24th October 2011.


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