The Role of Peganum harmala Ethanolic Extract and Type II Toxin Antitoxin System in Biofilm Formation

Abstract

Toxin antitoxin system is a regulatory system that antitoxin inhibits the toxin. We aimed to determine the role of TA loci in biofilm formation in K. pneumoniae clinical and environmental isolates; also inhibition of biofilm formation by Peganum harmala. So, 40 K. pneumoniae clinical and environmental isolates were subjected for PCR to determine the frequency of mazEF, relEB, and mqsRA TA loci. Biofilm formation assay subjected for all isolates. Then, P. harmala was tested against positive biofilm formation strains. Our results demonstrated that relBE TA loci were dominant TA loci; whereas mqsRA TA loci were negative in all isolates. The most environmental isolates showed weak and no biofilm formation while strong and moderate biofilm formation observed in clinical isolates. Biofilm formations by K. pneumoniae in 9 ug/ml concentration were inhibited by P. harmala. In vivo study suggested to be performed to introduce Peganum harmala as anti-biofilm formation in K. pneumoniae.

Key words

Klebsiella pneumoniae - biofilm formation - Peganum harmala

• References

• 1 Naparstek L, Carmeli Y, Navon-Venezia SH. et al. Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother 2014; 69: 1027-1034
• 2 Gonzalez Barrios AF, Zuo R, Hashimoto Y. et al. Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (Mqsr, B3022). J Bacteriol 2006; 188: 305-316
• 3 Kim Y, Wang X, Ma Q. et al. Toxin-Antitoxin systems in Escherichia coli influence biofilm formation through Yjgk (Taba) and fimbriae. J Bacteriol 2009; 191: 1258-1267
• 4 Ghafourian S, Raftari M, Sadeghifard N. et al. Toxin-antitoxin systems: classification, biological function and application in biotechnology. Curr Issues Mol Biol 2014; 16: 9-14
• 5 Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004; 2: 95-108
• 6 Zubair M, Malik A, Ahmad J. et al. A study of biofilm production by gram-negative organisms isolated from diabetic foot ulcer patients. Biol Med 2011; 3: 147-157
• 7 Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet 2001; 358: 135-138
• 8 Karimi S, Ghafourian S, Taheri Kalani M. et al. Association between toxin-antitoxin systems and biofilm formation. Jundishapur. J Microbiol 2015; 8: e14540
• 9 Thompson JD, Manicacci D, Tarayre M. Thirty-five years of thyme: a tale of two polymorphisms. Why so many females? Why so many chemotypes?. J BioSci 1998; 48: 805-815
• 10 Moloudizargari M, Mikaili P, Aghajanshakeri SH. et al. Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. Pharmacogn Rev 2013; 7: 199-212
• 11 Mowat E, Rajendran R, Williams C. et al. Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation. FEMS Microbiol Lett 2010; 313: 96-102
• 12 Soheili S, Ghafourian S, Sekawi Z. et al. The mazEF toxin-antitoxin system as an attractive target in clinical isolates of Enterococcus faecium and Enterococcus faecalis. Drug Des Devel Ther 2015; 9: 2553-2561
• 13 Ghafourian S, Good L, Sekawi Z. et al. The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii. Mem Inst Oswaldo Cruz 2014; 109: 502-505
• 14 Sadeghifard N, Soheili S, Sekawi Z et al. Is the mazEF toxin-antitoxin system responsible for vancomycin resistance in clinical isolates of Enterococcus faecalis? GMS Hyg Infect Control 2014; 9:
• 15 Yamaguchi Y, Park JH, Inouye M. Toxin-Antitoxin systems in bacteria and archaea. Annu Rev Genet 2011; 45: 61-79
• 16 Soo VW, Wood TK. Antitoxin MqsA represses curli formation through the master biofilm regulator CsgD. Sci Rep 2013; 11: 3186
• 17 Pandey DP, Gerdes K. Toxin-Antitoxin Loci Are Highly Abundant in Free-Living but Lost from Host-Associated Prokaryotes. Nucl Acids Res 2005; 33: 966-976
• 18 Pecota DC, Wood TK. Exclusion of T4 phage by the Hok/Sok killer locus from plasmid R1. J Bacteriol 1996; 178: 2044-2050