Laboratory of Regulation of Expression of Microorganisms’ Genes | Institute of Molecular Genetics

Khmel Inessa Aleksandrovna


Main directions of research

  1. Bacterial plasmids: molecular, genetic and functional investigations  (1973—1990).
  2. Antibiotics of enterobacteria microcins, genetic determinants of synthesis, mechanisms of the action (1990—2006).
  3. Quorum Sensing (QS) regulation of gene expression of bacteria: molecular, genetic and functional studies, the role in the regulation of cell processes. Regulation of the bacterial biofilms formation  (2003 – at present time).
  4. Volatile organic compounds (VOC) synthesized by  bacteria:  nature, action on various biological objects, mechanisms of the action, functional role  (2011 – at present time ).
  5. Interactions of metal nanoparticles with bacterial cell. Biogenesis of nanoparticles using bacterial cultures ( 2009  – at present time).

Main scientific results

I. Bacterial plasmids: molecular, genetic and functional investigations  (1973—1990).
Genetic control and regulation of the replication of the group of multicopy  colicinogenic  plasmids  have been studied. Plasmids fragments  responsible for its autonomous replication were identified and nucleotide sequence and structure of the replication apparatus  determined.
Mechanisms of the induction of the synthesis of colicins (antibiotics of protein nature encoded plasmid genes) were investigated.  The structure of plasmid ColD colicin operon have been determined.
The mechanism of the protective and enhancing the induced mutagenesis action of colicinogenic  plasmids ColIb and ColIa have been elucidated. It was found that the effect of the plasmids under UV irradiation caused by the action of the plasmid-encoded products - functional analogs of the products of chromosomal genes umuC and umuD
II.  Antibiotics of enterobacteria microcins, genetic determinants of synthesis, mechanisms of the action (1990—2006).
The ability of enterobacteria to synthesize antibiotics microcins was studied, the plasmids nature of genes involved in their synthesis has been shown. Microcin C51, nucleotide-peptide antibiotic with unusual structure, found in the Laboratory, and genetic determinants of its synthesis have been investigated. The nucleotide sequence of the microcin operon has been determined and polypeptides related to the synthesis of microcin and immunity to it of producer cells were identified.  The possibility of horizontal transfer of gene cluster associated with the synthesis of microcin C51 has been shown.
The mechanism of inhibition of translation by microcin C has been determined. It was shown that microcin processed inside sensitive cells, forming a modified aspartyl adenylate, a competitive inhibitor of aspartyl-tRNA synthetase (together with K.V. Severinov group).
The regulation of expression of bacterial genes  functioning in the absence of active cell growth was studied on the model of microcin C51 operon. It is shown that the expression of the operon is activated when  E. coli cells passed in the stationary phase of growth, and implemented with the participation of the complex regulatory network including  four global transcription regulators. The detailed analysis and site-directed mutagenesis of the promoter region of the microcin operon has been performed and sites essential to the regulation of expression of the operon have been determined.
III.  Quorum Sensing (QS) regulation of gene expression of bacteria: molecular, genetic and functional investigations, role in the regulation of cell processes ( 2003 -  at present time ).
The ability to synthesize autoinducers of Quorum Sensing (QS) systems of regulation of gene expression of bacteria N-acyl-homoserine lactones (AHL) in more than 200 strains of soil-born and rhizosphere pseudomonads isolated in various geographic zones was studied; AHL synthesis was observed in 17% strains investigated.
QS systems of model strains  Pseudomonas chlororaphis, Burkholderia cenocepacia, Serratia proteamaculans were studied in details. Genes of QS systems have been cloned and sequenced, their organization was defined, the role of global transcription regulators in the control of the expression of  QS systems genes was explained. The data on the role of QS systems in the regulation of cellular processes of bacteria have been  obtained.
The stimulating action of subinhibitory concentrations of nitrofurans, NO donors, plant phenolic compounds, some phytohormones, including salicylic acid, and hydrogen peroxide on the bacterial biofilms formation  have been shown. In the case of the action of phenols and hydrogen peroxide this effect was associated with QS regulation of bacterial genes expression. As the concentrations of these compounds increase they inhibited the formation of biofilms. The results  obtained are important for medicine because pathogenic bacteria living in biofilms are much more resistant to the action of antibacterial agents than planctonic bacteria. Therefore, data on biofilm formation stimulation by low concentrations of antibacterial agents must be considered in defining of schemes of antibacterial therapy using preparations containing these compounds or their derivatives.
IV.  Volatile organic compounds (VOC), synthesized by bacteria: nature,   action on various biological objects, mechanisms of action, functional role (2011-at present time).
The synthesis of volatile organic compounds (VOCs)  by  Pseudomonas and Serratia strains was studied, the individual VOCs  were identified (in collaboration with Dr. L. Chernin, Jerusalem University, Israel). It was shown that total pools of volatiles and individual VOCs (dimethyldisulfide, ketones)  suppressed the growth of phytopathogenic bacteria and fungi, cyanobacteria, bacterial biofilms formation.  They could also exert a lethal effect on insects (Drosophila) and nematodes.
It was shown for the first time that VOCs inhibit functioning of QS regulation systems of bacteria.
V.  Interactions of metal nanoparticles with bacterial cell. Biogenesis of nanoparticles using bacterial cultures ( 2009  – at present time).
The action  of silver and gold nanoparticles and ions on the growth, viability of bacteria  and on bacterial biofilms was studied.
 Mutations in genes responsible for the repair of DNA containing oxidative lesions were shown to increase the sensibility of  E. coli cells to silver nanoparticles and silver ions. This suggests that these genes may be involved  in the repair of damaged DNA caused by silver ions and  nanoparticles.
The data about the important role of transport proteins porins in antibacterial effect of silver nanoparticles have been obtained.
The experiments on obtaining nanoparticles of gold  by "green synthesis" in cultures of cyanobacteria and Azotobacter were performed; the importance of the process of nitrogen fixation for the biogenesis of nanoparticles have been established.


  1. Khmel, I.A., V.M. Bondarenko, I.M. Manokhina, E.I. Basyuk, A.Z.   Metlitskaya, V.A. Lipasova,   and Yu. M  Romanova.   Isolation and characterization of Escherichia coli strains producing  microcins of B and C types. FEMS Microbiol. Lett. 1993, v. 111, 269-274. 
  2. Kurepina, N.E., E.I. Basyuk, A.Z. Metlitskaya, D.A.Zaitsev,  and I.A . Khmel. 1993.  Cloning and  mapping of the genetic determinants  for microcin C51 production and immunity. Mol .Gen.   Genet. 1993, v.  241, 700-706. 
  3. Metlitskaya,  A.Z., G.S. Katrukha, A.S. Shashkov, D.A. Zaitsev, Ts.A. Egorov,  I.A. Khmel.  Structure of microcin C51, a new antibiotic with a broad spectrum of activity. FEBS Letters, 1995, v.  357, 235-238. 
  4. Khmel I.A., Sorokina T.A., Lemanova N.B., Lipasova V.A., Metlitski O.Z., Burdeinaya T.V., Chernin L.S. Biological control of crown gall in grapewine and raspberry by two Pseudomonas spp. with a wide spectrum of antagonistic activity. Biocontrol Science and Technology, 1998, v. 8, 45-57. 
  5. Fomenko D., Veselovskii A., Khmel I. Regulation of the microcin  C51 operon expression: the role of global regulators of transcription. Research in   Microbiology,  2001, v. 152, 469-479. 
  6. Fomenko D.M., Metlitskaya A.Z., Peduzzi J., Goulard C., Katrukha G.S., Gening, L.V., Rebuffat S., Khmel I.A.  Microcin C51 plasmid genes: possible  source of  horizontal gene transfer. Antimicrobial Agents and Chemotherapy, 2003, v. 47,  2868-2874.
  7. Veselova M., Kholmeckaya M., Klein S., Voronina E., Lipasova V.,  Metlitskaya A., Mayatskaya A., Lobanok E., Khmel I., Chernin L.  Production of N-acylhomoserine lactone signal molecules by Gram-negative soil-borne and plant- associated  bacteria. Folia Microbiol., 2003, v. 48, 794-798.
  8. Сhernin L.,  Klein S.,  Khmel I.,   Veselova M., Metlitskaya  A., Bass I.,  Mayatskaya  A.,    Kholmeckaya M., Lobanok L.,  Liu  Xiaoguang,   Chet I.  Intracellular communication  in the environment and  biocontrol  activity of  plant-associated bacteria producing N-acyl homoserine  lactone  signal molecules.  Scientific Israel - Technological Advantages,  2004, v. 6,  No 1-2  "Environmental  Engineering&Energy Engineering", pp. 19-30.          
  9. Khmel I.A. Regulation of expression of bacterial genes in the absence of active cell  growth. Russian Journal of Genetics, 2005, v. 41, 968-984.
  10. Khmel I.A., Ovadis M.I., Mayatskaya A.V., Veselovskii A.M., Bass I.A., Lipasova V.A., Bolshoy A., Chet I., Chernin L.S. Activity of Serratia plymuthica IC1270 gene chiA promoter region in Escherichia coli mutants deficient in global regulators of transcription. J. Basic Microbiol. 2005,  v. 45, 426-437.
  11. Khmel I.A., Metlitskaya A.Z. Quorum Sensing regulation of gene expression: a promising target for drugs against bacterial pathogenicity. Molecular Biology (Russian)  2006,  40, 169-182.
  12. Metlitskaya A., Kazakov T., Kommer A., Pavlova O., Praetorius-Ibba M., Ibba M.,  Krasheninnikov I., Kolb V., Khmel I.,  Severinov K. Aspartyl-tRNA synthetase is  the  target of peptidenucleotide antibiotic microcin C. J.Biol. Chem., 2006, v. 281, 18033-18042.
  13. Belik AS, Zavil'gel'skiĭ GB, Khmel IA. Influence of mutations at genes of global  transcriptional regulators on production of autoinducer AI-2 of Quorum Sensing system of Escherichia coli. Russian J. of Genetics, 2008 v., 44,1184-1190.
  14. Veselova M, Klein Sh, Bass IA, Lipasova VA, Metlitskaia AZ, Ovadis MI, Chernin LS, Khmel IA. Quorum sensing systems of regulation, synthesis of phenazine antibiotics, and antifungal activity in rhizospheric bacterium Pseudomonas chlororaphis 449. Russian J. of Genetics, 2008, v. 44, 1617-1626.
  15. Shedova E., Lipasova V., Velikodvorskaya G., Ovadis M., Chernin L., Khmel I. Phytase activity and its regulation in a rhizospheric strain of Serratia plymuthica. Folia   Microbiol. 2008,  v. 53, 110-114.
  16. Zaitseva J., Granik V., Belik A., Koksharova O., Khmel I. Effect of nitrofurans and NO  generators on biofilm formation by Pseudomonas aeruginosa PAO1 and Burkholderia  cenocepacia 370. Research in Microbiology. 2009, v. 160, 353-357.
  17. Lipasova V.A., Atamova E.E., Veselova M.A., Tarasova N.N., Khmel I.A. Expression of N-acyl-homoserine lactonase AiiA gene affects properties of   rhizospheric strain Pseudomonas chlororaphis 449. Russian J. of Genetics, 2009,  v. 45, 38-42.
  18. Veselova M., Lipasova V., Protsenko M.A., Buza N., Khmel I.A. GacS-Dependent  regulation of  enzymic and antifungal activities and synthesis of N-acylhomoserine  lactones in rhizospheric  strain Pseudomonas chlororaphis 449. Folia  Microbiologica. 2009,  v. 54, 401–408.
  19. Zaitseva Iu.V, Voloshina P.V., Liu X., Ovadis M.I., Berg G., Chernin .S., Khmel I.A. Involvement of the global regulators GrrS, RpoS, and SplIR in formation of biofilms in Serratia plymuthica. Russian J. of Genetics, 2010, v. 46, 616-621.
  20. Nadtochenko V.A., Radtsig M.A., Khmel I.A. Antimicrobial effect of metallic and  semiconductor nanoparticles. Nanotechnologies in Russia, 2010, v. 5, 277-289.
  21. Dandurishvili N., Toklikishvili N., Ovadis M.,  Eliashvili P., Giorgobiani N., Keshelava R., Tediashvili M., Vainshtein A., Khmel I., Szegedi E., Chernin L. Broad-range antagonistic rhizobacteria Pseudomonas fluorescens and Serratia plymuthica suppress Agrobacterium crown gall tumours on tomato plants. J. Appl.Microbiol. 2011, 110 (1), 341-352.
  22. Chernin L., Toklikishvili N., Ovadis M., Kim S., Ben-Ari J., Khmel I., Vainstein A. Quorum-sensing quenching by rhizobacterial volatiles. Environmental Microbiology Reports, 2011, v. 3,  698-704.
  23. Veselova MA, Lipasova VA, Zaĭtseva IuV, Koksharova OA, Chernukha MIu,  Romanova IuM, Khmel IA. Mutants of Burkholderia cenocepacia with a change in synthesis of N-acyl-homoserine lactones--signal molecules of Quorum Sensing regulation. Russian J. of Genetics,. 2012, v. 48, 608-616.
  24. M.A. Radzig, V.A. Nadtochenko, O.A. Koksharova , J. Kiwi, V.A. Lipasova ,   I.A. Khmel. Antibacterial effects of silver nanoparticles on Gram-negative bacteria: influence on the growth and biofilms formation, mechanisms of action. Colloids and Surfaces B: Biointerfaces, 2013, v. 102, 300-306.
  25. Plyuta V.A., Zaitseva J, Lobakova E, Zagoskina N, Kuznetsov A,  Khmel I. Effect of plant phenolic compounds on biofilm formation by Pseudomonas  aeruginosaAPMIS. 2013, v. 121, 1073-1081.
  26. Chernin L., Toklikishvili N., Ovadis M., Khmel I. Quorum-Sensing quenching by  volatile organic compounds emitted by rhizosphere bacteria. In: Molecular Microbiol. Ecology of the Rhizosphere, v. 2, Ed. By Frans J. de     Bruijn, 2013, John Wiley & Sons, Inc. P. 791-800.
  27. Plyuta V.A., Lipasova V.A., Kuznetsov A.E., Khmel I.A. Effect of salicylic, indole-3-acetic, gibberellic, and abscisic acids on biofilm formation by Agrobacterium tumefaciens C58 and Pseudomonas aeruginosa PAO1. Applied Biochemistry and Microbiology, 2013, V. 49 N 8, P. 706-710
  28. Zaitseva Yu.V., Popova A.A., Khmel I.A. Quorum Sensing regulation in bacteria of the family Enterobacteriaceae. Russian J. of Genetics, 2014, v. 50, 323-340.
  29. A.  A. Popova, O. A. Koksharova, V. A. Lipasova, Ju. V. Zaitseva, O. A. Katkova-Zhukotskaya, S. Iu. Eremina, A. S. Mironov, L. S. Chernin, I. A. Khmel. Inhibitory and toxic Effects of Volatiles emitted by Strains of Pseudomonas and Serratia on Growth and Survival of selected Microorganisms, Caenorhabditis elegans and Drosophila melanogaster.  BioMed Research International,   Volume 2014, Article ID 125704, 11 pages,