RECENT PROMISING ADVANCES IN DEVELOPMENT OF ANTIMICROBIAL AGENTS: A REVIEW

  • Mudasir Maqbool Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India
  • Geer Mohamed Ishaq Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Abstract

Antimicrobial resistance is a serious global threat. There is a global menace of antibiotic resistant “super bug”, though the extent and the severity of the problem varies. Resistance hampers therapeutic options and drives clinicians to use newer and more expensive drugs. In serious cases, multi-resistance provides no treatment options. To overcome resistance, a continuous supply of new antibiotics offers an obvious way; but the pipeline of agents in development by the Pharmaceutical industry is very limited. There is an ever-evolving need to develop and evaluate newer alternative strategies for countering a worsening clinical situation to overcome resistance and reduce the morbidity and mortality associated with infections caused by antibiotic-resistant bacteria. The widespread distribution of Antimicrobial resistance has not been paralleled by the development of newer antimicrobials. This happens due to the process of drug discovery and clinical trials of new antimicrobials taking longer time and only a fewer new agents been approved for use. In modern era, where obstacles like chemo-resistance and mutations torment medicine, scientists across the world are looking to adapt lateral approaches in encountering diseases.


Keywords: antimicrobial resistance, super bug, antibiotics

Downloads

Download data is not yet available.

Author Biographies

Mudasir Maqbool, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir,  Hazratbal Srinagar-190006, Jammu and Kashmir, India

Geer Mohamed Ishaq, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir,  Hazratbal Srinagar-190006, Jammu and Kashmir, India

References

1. Dr. Margaret Chan, Director General-World Health Organization. Available from htpp://www.who.int/world-health-day/2011
2. Appelbaum PC. 2012 and beyond: Potential for the start of a second pre-antibiotic era? J Antimicrob Chemother. 2012; 67(9):2062-8. doi: 10.1093/jac/dks213.
3. Fox JL. The business of developing antibacterials. Nat Biotechnol 2006; 24:1521–8.
4. Projan SJ, Shales DM. Antibacterial drug discovery: is it all downhill from here? Clin Microbial Infect, 2004; 10 (Suppl 4):18-22.
5. Chang Q., Wang W., Regev-Yochay G., Lipsitch M., and Hanage W.P. Antibiotics in agriculture and risk to human health: how worried should we be ? Evol Appl. 2015 Mar; 8(3): 240–247. doi: 10.1111/eva.12185
6. Murima P, McKinney JD, Pethe K. Targeting bacterial central metabolism for drug development. Chem Biol. 2014; 21(11):1423-32. doi: 10.1016/j.chembiol.2014.08.020.
7. Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005 Jan 14; 307(5707):223-7.
8. K Pethe, P Bifani, J Jang, S Kang, S Park, S Ahn S., et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis .Nat Med. 2013; 19(9):1157-60. doi: 10.1038/nm.3262.
9. Sass P., and Brötz-Oesterhelt H. Bacterial cell division as a target for new antibiotics. Curr Opin Microbiol. 2013; 16(5):522-30. doi: 10.1016/j.mib.2013.07.006.
10. Krol,E., de Sousa Borges, A., da Silva, I., Polaquini, C. R., Regasini, L. O., Ferreira, H., et al. (2015). Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes. Front Microbiol. 2015; 29(6):390. doi: 10.3389/fmicb.2015.00390.
11. Foley T. L., and Simeonov, A. Targeting iron assimilation to develop new antibacterials. Expert Opin Drug Discov. 2012; 7(9):831-47. doi: 10.1517/17460441.2012.708335.
12. Urfer M., Bogdanovic J., Lo Monte F., Moehle K., Zerbe K., Omasits U., et al. A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli. J Biol Chem. 2016; 291(4):1921-32. doi: 10.1074/jbc.M115.691725.
13. Rao C. V. S., De Waelheyns E., Economou A., and Anné J. Antibiotic targeting of the bacterial secretory pathway. Biochim Biophys Acta. 204; 1843(8):1762-83. doi: 10.1016/j.bbamcr.2014.02.004.
14. Hooper D. C., and Jacoby G. A. Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci. 2015; 1354:12-31. doi: 10.1111/nyas.12830.
15. Shaw K. J. , Rather P. N., Hare R. S., and Miller, G. H. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev. 1993; 57(1):138-63.
16. Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Microbiol Mol Biol Rev. 2003; 67(4):593-656.
17. Sun J., Deng Z., and Yan A. Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun. 2014: 453(2):254-67. doi: 10.1016/j.bbrc.2014.05.090.
18. Opperman, T. J., and Nguyen, S. T. Recent advances toward a molecular mechanism of efflux pump inhibition. Front Microbiol. 2015; 6:421. doi: 10.3389/fmicb.2015.00421.
19. Pule C. M., Sampson S. L., Warren R. M., Black P. A., van Helden P. D., Victor T. C., et al. Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy. J Antimicrob Chemother. 2016; 71(1):17-26. doi: 10.1093/jac/dkv316.
20. King D.T., and Strynadka N. C. (2013). Targeting metallo-beta-lactamase enzymes in antibiotic resistance. Future Med Chem. 2013; 5(11):1243-63. doi: 10.4155/fmc.13.55.
21. Dharmesh Harwani The Great Plate Count Anomaly and the Unculturable Bacteria International Journal of Scientific Research, 2013; 2(9).
22. Cesar A. Arias, M.D., Ph.D., and Barbara E. Murray, M.D. A New Antibiotic and the Evolution of Resistance., N Engl J Med. 2015 ;3 72(12):1168–1170.
23. Ling LL, Schneider T, Peoples AJ et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015; 517(7535):455-9. doi: 10.1038/nature14098.
24. Kaeberlain et al, “Isolating ‘uncultivable’ Microorganisms in Pure Culture in Simulated Natural Environment,”Science 2002; 296(5570):1127-1129.
25. Nichols et al. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl. Environ. Microbiol. 2010; 76(8):2445-2450.
26. Fleming, A. 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. 1929; 10(3):226–236.
27. Marr AK, Gooderham WJ, Hancock RE. Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol. 2006; 6(5):468-72.
28. Hancock RE, Lehrer R. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 1998; 16(2):82-8.
29. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005; 3(3):238-50.
30. Shai Y. Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta. 1999; 1462(1-2):55-70.
31. Huang Y, Huang J, Chen Y. Alpha-helical cationic antimicrobial peptides: relationships of structure and function. Protein Cell. 2010; 1(2):143-52. doi: 10.1007/s13238-010-0004-3.
32. Peters BM, Shirtliff ME, Jabra-Rizk MA. Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog. 2010; 6(10):e1001067. doi: 10.1371/journal.ppat.1001067.
33. McGrath DM, Barbu EM, Driessen WHP, Lasco TM, Tarrand JJ, Okhuysen PC, Kontoyiannis DP, Sidman RL, Pasqualini R, Arap W. Mechanism of action and initial evaluation of a membrane active all-D-enantiomer antimicrobial peptidomimetic. Proc Natl Acad Sci USA. 2013; 110:3477–82. http://dx.doi.org/10.1073/pnas.1221924110.
34. Barbu EM, Shirazi F, McGrath DM, Albert N, Sidman RL, Pasqualini R, Arap W, Kontoyiannis DP. An antimicrobial peptidomimetic induces mucorales cell death through mitochondria-mediated apoptosis. PLoS One. 2013; 8(10):e76981. doi: 10.1371/journal.pone.
35. Griebling TL. Urologic diseases in America project: trends in resource use for urinary tract infections in women. J Urol. 2005; 173(4):1281-7.
36. Gupta K, Hooton TM, Stamm WE. Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med. 2001; 135(1):41-50.
37. Chen SL, Hung CS, Pinkner JS, Walker JN, Cusumano CK, Li Z, Bouckaert J, Gordon JI, Hultgren SJ. Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding. Proc Natl Acad Sci USA. 2009; 106(52):22439-44. doi: 10.1073/pnas.0902179106.
38. Cusumano CK, Pinkner JS, Han Z, Greene SE, Ford BA, Crowley JR, Henderson JP, Janetka JW, Hultgren SJ. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci Transl Med. 2011; 3(109):109ra115. doi: 10.1126/scitranslmed.3003021.
39. Han Z, Pinkner JS, Ford B, Chorell E, Crowley JM, Cusumano CK, Campbell S, Henderson JP, Hultgren SJ, Janetka JW. Lead optimization studies on FimH antagonists: discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides. J Med Chem. 2012; 55(8):3945-59. doi: 10.1021/jm300165m.
40. Tran N, Mir A, Mallik D, Sinha A, Nayar S, Webster TJ. Bactericidal effect of iron oxide nanoparticles on Staphylococcus aureus. Int J Nanomedicine. 2010; 5:277–283.
41. Hazan R, He J, Xiao G, Dekimpe V, Apidianakis Y, Lesic B, Astrakas C, Déziel E, Lépine F, Rahme LG. Homeostatic interplay between bacterial cell-cell signaling and iron in virulence. PLoS Pathog. 2010 Mar 12;6(3):e1000810. doi: 10.1371/journal.ppat.1000810.
42. Ng W, Bassler BL. Bacterial quorum-sensing network architectures. Annu Rev Genet.2009; 43:197–222. doi: 10.1146/annurev-genet-102108-134304.
43. Que Y, Hazan R, Ryan CM, Milot S, Lépine F, Lydon M, Rahme LG. Production of Pseudomonas aeruginosa Intercellular Small Signaling Molecules in Human Burn Wounds. J Pathog.2011; 2011:549302. doi: 10.4061/2011/549302.
44. Lesic B, Lépine F, Déziel E, Zhang J, Zhang Q, Padfield K, Castonguay M, Milot S, Stachel S, Tzika AA, Tompkins RG, Rahme LG. Inhibitors of pathogen intercellular signals as selective anti- infective compounds. PLoS Pathog. 2007; 3(9):1229-39.
45. Habich D, Von Nussbaum F. Platensimycin, a new antibiotic and “superbug challenger” from nature. ChemMedChem. 2006; 1(9):951-4.
46. Clatworthy AE, Pierson E, Hung DT. Targeting virulence: A new paradigm for antimicrobial therapy. Nat Chem Biol. 2007; 3(9):541-8.
47. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006; 311(5768):1770-3.
48. Wilkinson A, Holmes S, Pitts K. Proceedings of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, USA: 2007. Sep 17-20, SASP: A novel antibacterial DNA binding protein and its targeted delivery to Staphylococcus aureus. Abstract F1-2132.
49. Randhawa GK, Kullar JS, Rajkumar. Bioenhancers from mother nature and their applicability in modern medicine. Int J Appl Basic Med Res. 2011; 1(1):5-10. doi: 10.4103/2229-516X.81972.
50. Ejim L, Farha MA, Falconer SB, Wildenhain J, Coombes BK, Tyers M, et al. Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat Chem Biol. 2011; 7(6):348-50. doi: 10.1038/nchembio.559.
51. Coutinho HD, Lobo KM, Bezerra DA, Lobo I. Peptides and proteins with antimicrobial activity. Indian J Pharmacol. 2008; 40:3–9.
52. Asahina Y, Nagae O, Sato T, Takadoi M, Ohata K, Shibue T, et al. Proceedings of the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Disease Society of America (IDSA) 46th Annual Meeting. Washington DC: 2008. Oct 25-28, AM-3005: Synthesis and in vitro antibacterial activity of novel mutilin-quinolone hybrid antibacterial agent (F1-2030).
53.Meers P, Neville M, Malinin V, Scotto AW, Sardaryan G, Kurumunda R, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother. 2008; 61(4):859-68. doi: 10.1093/jac/dkn059.
54. Nautiyal CS, Chauhan PS, Nene YL. Medicinal smoke reduces airborne bacteria. J Ethnopharmacol. 2007; 114(3):446-51.
Statistics
44 Views | 32 Downloads
How to Cite
Maqbool, M., & Ishaq, G. M. (2018). RECENT PROMISING ADVANCES IN DEVELOPMENT OF ANTIMICROBIAL AGENTS: A REVIEW. Journal of Drug Delivery and Therapeutics, 8(5-s), 82-86. https://doi.org/10.22270/jddt.v8i5-s.1959
Section
Review