Isolation and biochemical characterization of a novel antimicrobial agent produced by Streptomyces violaceusniger isolated from Yemeni soil

Shadia A. Fathy, Mohamed R. Mohamed, Mostafa M. Elhady, Mohamed H. Al-habal


Background: Infections caused by multidrug-resistant bacteria present daily challenges to infectious disease physicians in hospitals throughout the world and these pathogens are spreading into the community. The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infective research.

Methods: The experiments were carried out to search for new natural antibiotics through isolation of various Streptomyces strains from different soil samples from Yemen and studying the antimicrobial effects of metabolites that produced. In the same time, the toxicological and biochemical effects of the extracted antibiotic on animals were studied.

Results: Streptomyces violaceusniger, was isolated from Yemeni soil sample produced active metabolite that was designated faqihmycin has substantial antimicrobial potential against different microbial species. Investigations into the possible mode of action of faqihmycin revealed that it affects cell wall synthesis and intracellular macromolecule contents of the Gram-positive bacteria Bacillus subtilis. Toxicity studies of faqihmycin confirmed the hepatotoxicity of faqihmycin, there is no strong evidence to suggest that it is nephrotoxic.

Conclusions: Further studies with Faqihmycin are needed in order to elucidate its detailed mechanism of action on bacterial cells, as well as studies with Faqihmycin with different doses in order to determine its potential therapeutic use.



Antimicrobial agent, Streptomyces, Antibiotic resistance, Hepatotoxicity, Nephrotoxicity

Full Text:



Kohanski M, Dwyer D, Collins, J. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol. 2010;8(6):423–35.

Bugg T, Braddick D, Dowson C, Roper D. Bacterial cell wall assembly: still an attractive antibacterial target. Trends Biotechnol. 2011;29:167-73.

Payne D, Gwynn M, Holmes D, Pompliano L. Drugs for bad bugs: Confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6:29-40.

Hopwood DA. Streptomyces in nature and medicine: the antibiotic makers. New York, USA: Oxford University Press; 2007.

Devasahayam G, Scheld W, Hoffman P. Newer Antibacterial Drugs for a New Century. Expert Opin Investig Drugs. 2010;19:215-34.

Wang J, Soisson S, Young K, Shoop W, Kodali S, Galgoci A, et al. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature. 2006;441:358-61.

Clardy J, Fischbach M, Walsh C. New antibiotics from bacterial natural products. Nat Biotechnol. 2006;24:1541-50.

Baltz R. Marcel Faber Roundtable: Is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration? J Ind Microbiol Biotechnol. 2006;33:507-13.

Hopwood D. Complex Enzymes in Microbial Natural Product Biosynthesis. In Methods In Enzymology. vol. 458, Part A overview particales and peptides. USA: Academic press Elsevier Inc; 2009:1-141.

Shirling D, Gottlieb S. Methods for characterization of Streptomycesspecies. Int J Syst Bacteriol. 1966;16:3313-40.

Cooper K. The theory of antibiotic inhibition zones. In: Kavanagh F edr. Analytical microbiology, volume II, New York, USA: Academic Press, Inc; 1972:13–30.

Waksman S. The Actinomycetes, classification, identification and descriptions of Genera and Species. Baltimore: The Williams & Wilkins Comp; 1967; vol. 2:61.

Boudjella H, Bouti K, Zitouni A, Mathieu F, Lebrihi A, Sabaou N. Isolation and partial characterization of pigment-like antibiotics produced by a new strain of Streptosporangium isolated from an Algerian soil. J Appl Microbiol. 2007;103:228-36.

Schmidt G, Thannhauser S. A method for extraction and estimation of deoxyribonucleic acid, ribonucleic acid and phosphoproteins in tissues. J Biol Chem. 1945;161:83-9.

Toribarn J, Chen P, Warner H. Assay of inorganic phosphate, total phosphatases. In: Elizabeth F, Vitor G, eds. “Methods in Enzymalogy”. Academic press, 1956;3:55-66.

Knight J, Andreson S, Rawle J. Sulfo-Phosphovanillin reaction for the estimation of total serum lipids. Clin Chem. 1972;18:199-202.

Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem. 1976;72:248-54.

Lewy G, McAllan A. Colorimetric methods for free and acetylated hexosamines. In: Methods in Enzymology. Academic press, 1959;3:58-66.

Nagai K, Yamaki H, Suzuki H, Tanaka N, Umezawa H. Decrease of melting temperature and single strand scission of DNA by Bleomycin in the presence of 2–mercaptoethanol. J Antibiot (Tokyo). 1969;22:569-73.

Sakuri Y. Methods for determining acquired resistance to drugs. Natl. Cancer Inst. Monogr. 1964;16:207-39.

Laemmli U. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-5.

Baß R, Günzel P, Henschler D, Konig J, Lorke D, Neubert D, Schiitz E, Schuppan D, Zbinden G. LD50 versus acute toxicity: critical assessment of the methodology currently in use. Arch Toxicoll. 1982;51:183-6.

Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957;28:56-63.

Kind P, King E. Estimation of plasma phosphatase by determination of hydrolyzed phenol with antipyrine. J Clin Pathol. 1954;7:322-6.

Cooper G. Methods for determining the amount of glucose in blood. Crit Rev Clin Lab Sci. 1973;4(2):101-45.

Henry R, Cannon D, Winkelman J. (1974): Clinical Chemistry-Principles and Technics, 2nd ed. Harper and Row, New York, USA; 1974:543-552.

Kaplan A. Urea: In: Kaplan L, Pesce A, eds. Clinical chemistry: theory, analysis, and correlation. St Louis, Toronto: Mosby Co. Princeton; 1984a:1257-1260.

Fossati P, Prencipe L, Berti G. Use of 3, 5-dichloro-2 hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin. Chem. 1980;26:227-31.

Doumas B, Watson W, Biggs H. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta. 1971;31(1):87-96.

Kaplan A. Lipids. In: Kaplan L, Pesce A, eds. Clinical chemistry: theory, analysis, and correlation. Princeton, Toronto: Mosby Co. St Louis; 1984b:918-919.

Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem. 1973;19:1350-6.

Bucolo G, David R. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem. 1973;19:476-82.

Donadio S, Maffioli S, Monciardini P, Sosio M, Jabes D. Antibiotic discovery in the twenty-first century: current trends and future perspectives. J Antibiot. 2010;63:423-30.

Rasko D, Webster D, Sahl J, Bashir A, Boisen N, Scheutz F, et al. Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany. N Engl J Med. 2011;365:709-17.

Turner M. Phage on the rampage: Antibiotic use may have driven the development of Europe's deadly E. coli. Nature; 2011.

Payne D, Gwynn M, Holmes D, Pompliano L. Drugs for bad bugs: Confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 2007;6:29-40.

Butler M. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat. Prod. Rep. 2008;25:475-516.

Lodish H. In: “Molecular Cell Biology”. 4th ed. Library of Congress Cataloging-in-Publication Data; 2000:454-459.

Waring M, Markeoff A. The effect of antimicrobial drugs on protein synthesis using labeled precursor. J Mol pharmacol. 1999;10:214-224.

Novo D, Perlmatter N, Hunt R, Shapiro H. Multiparameter Flow Cytometric Analysis of Antibiotic Effects on Membrane Potential, Membrane Permeability, and Bacterial Counts of Staphylococcus aureus and Micrococcus luteus. Antimicrob. Agents Chemother. 2000;44:827-34.

Gruszecki W, Gagoś M, Hereć M, Kernen P. Organization of antibiotic amphotericin B in model lipid membranes. Cell Mol Biol Lett. 2003;8:161-70.

Axelsen P. A chaotic pore model of polypeptide antibiotic action. Biophys J. 2008;94:1549-50.

Roy B, Sarkar AK, Sengupta P, Dey G, Das A, Pal TK. Twenty-eight days repeated oral dose toxicity study of gemifloxacin in Wistar albino rats. Regul Toxicol Pharmacol. 2010;58:196-207.

Meyer D, Harvey J. Hepatobiliary and skeletal muscle enzymes and liver function tests. In: Veterinary Laboratory Medicine: Interpretation and Diagnosis. 3rd ed. WB. St. Louis, MO, USA: Saunders Co; 2004:169-192.

Ojo O, Kabutu F, Bello M, Babayo U. Inhibition of paracetamol-induced oxidative stress in rats by extracts of lemongrass (Cymbropogon citratus) and green tea (Camellia sinensis) in rats. Afr J Biotechnol. 2006;5:1227-32.

Farombi E, Nwankwo J, Wara S, Odutola B, Emerole G. Chloramphenicol and ampicillin-induced changes in rat hepatic esterase and amidase activities. Biosci Rep. 2000;20:13-9.

Sarich TC, Adams SP, Zhou T, Wright JM. Isoniazid-induced hepatic necrosis and steatosis in rabbits: absence of effect of gender. Can J Physiol Pharmacol. 1997;75:1108-11.

Fernandez-Bussy S, Akindipe O, Baz M, Gosain P, Rosenberg A, Zumberg M. Sirolimus-induced severe hypertriglyceridemia in a lung transplant recipient. Transplantation. 2010;89:481-2.

Skottova N, Krecman V. Sylimarin as a potential hypocholesterolaemic drug. Physiol. Res. 1998;47:1-7.

Cryer P. "Hypoglycemia". In: Jefferson L, Cherrington A, Goodman H, eds. For the American Physiological Society. Handbook of Physiology; Section 7, The Endocrine System. II. The endocrine pancreas and regulation of metabolism. New York: Oxford University Press; 2001:1057-1092.

Best C, Tailor N. Physiological bases of medical practice. 11th ed. Baltimore, New York, U.S.A: Williams and Wiklins; 1986.

Garber S, Pound M, Miller S. Hypoglycemia associated with the use of levofloxacin. Am J Health Syst Pharm. 2009;66:1014-9.

Bussing R, Gende A. Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction. Diabetes Care. 2002;25:1659-61.

Liu Y, Behr M, Small P, Kurn N. Genotypic determination of mycobacterium tuberculosis antibiotic resistance. J Clin Microbio. 2003;38:3656-62.

Basaria S, Braga M, Moore W. Doxycycline-induced hypoglycemia in a nondiabetic young man. South Med. J. 2002;95:1353-4.

Brogan S, Cahalan M. Gatifloxacin as a possible cause of serious postoperative hypoglycemia. Anesh. Analg. J. 2005;101:635-6.

Kendall C, Wooltorton E. People with diabetes should avoid antibiotic gatifloxacin. CMAJ. 2006; 174:1089-90.

Heritage J, Evans E, Killington R. Microbiology in Action. 2nd ed. UK: Cambridge University Press; 2000:247-66.

Waring M. Binding of Antibiotics to DNA, in Ciba Foundation Symposium 158. In: Chadwick DJ, Widdows K, eds. Host-Guest Molecular Interactions: From Chemistry to Biology. Chichester, UK: John Wiley & Sons, Ltd.; 2007:128-142.