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Recent updated aspects of colicins of Enterobacteriaceae

Aspectos atuais de colicinas de Enterobacteriaceae

Abstracts

The colicins are protein compounds produced by, and active against, Escherichia coli and others members of Enterobacteriaceae family. At least 34 different colicins have been described and found to share an interesting number of features. In the present review we focus on the major characteristics of colicins of gram-negative bacteria and explore their production and practical applications.The colicins are protein compounds produced by, and active against, Escherichia coli and others members of Enterobacteriaceae family. At least 34 different colicins have been described and found to share an interesting number of features. In the present review we focus on the major characteristics of colicins of gram-negative bacteria and explore their production and practical applications.

colicins; Escherichia coli; genetics; evolution; ecology


As colicinas são compostos proteináceos produzidos por Escherichia coli e outros membros da família Enterobacteriaceae, sendo ativas, principalmente, contra bactérias mais relacionadas. São conhecidos pelo menos 34 tipos diferentes de colicinas, apresentando algumas delas características intrigantes. Nesta revisão são abordados os principais aspectos das colicinas das bactérias gram-negativas, explorando desde sua produção até ass suas aplicações práticas.

colicinas; Escherichia coli; genética; evolução; ecologia


Recent updated aspects of colicins of Enterobacteriaceae

Aspectos atuais de colicinas de Enterobacteriaceae

Luciana CursinoI; Jan ŠmardaII; Edmar Chartone-SouzaII; Andréa M.A. NascimentoI

IDepartamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil

IIDepartment of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

Correspondence to Correspondence Av. Antônio Carlos, 6627 Departamento de Biologia Geral - Instituto de Ciências Biológicas Universidade Federal de Minas Gerais 31270-901, Belo Horizonte, MG, Brasil Fax: (+5531) 3499-2567 E-mail: amaral@icb.ufmg.br

MINI-REVIEW

ABSTRACT

The colicins are protein compounds produced by, and active against, Escherichia coli and others members of Enterobacteriaceae family. At least 34 different colicins have been described and found to share an interesting number of features. In the present review we focus on the major characteristics of colicins of gram-negative bacteria and explore their production and practical applications.The colicins are protein compounds produced by, and active against, Escherichia coli and others members of Enterobacteriaceae family. At least 34 different colicins have been described and found to share an interesting number of features. In the present review we focus on the major characteristics of colicins of gram-negative bacteria and explore their production and practical applications.

Key words: colicins, Escherichia coli, genetics, evolution, ecology

RESUMO

As colicinas são compostos proteináceos produzidos por Escherichia coli e outros membros da família Enterobacteriaceae, sendo ativas, principalmente, contra bactérias mais relacionadas. São conhecidos pelo menos 34 tipos diferentes de colicinas, apresentando algumas delas características intrigantes. Nesta revisão são abordados os principais aspectos das colicinas das bactérias gram-negativas, explorando desde sua produção até ass suas aplicações práticas.

Palavras-chave: colicinas, Escherichia coli, genética, evolução, ecologia

INTRODUCTION

The literature abounds with examples of antagonism between particular bacterial strains. In many instances the mediating agent is a bacteriocin. The bacteriocins are protein compounds produced by bacteria that inhibit or kill closed related species. Colicins are by far the best-characterized group of bacteriocins. They are produced by, and active against, Escherichia coli and others members of the Enterobacteriaceae family (79,98).

At least 34 different colicins have been described, 21 of them in greater detail (Table. 1) and they share an intriguing number of features. Under conditions of stress a fraction of colicinogenic bacteria are induced to produce colicin proteins. The type of stress causing the inductive activity needs to be better characterized. The release of colicins is in itself not always lethal to the producing cell. The colicinogenic bacteria are specifically protected against the colicins they produce. In addition, colicin gene clusters are plasmid encoded (82,98). A number of different applications have been suggested for colicins due to their broad spectrum of action. Examples of this kind include the control of diarrheal diseases caused by enteropathogenic bacteria, as food preservatives and others (61,98). In this review we focus on the most important aspects of these intriguing proteins called colicins.

PROTEIN STRUCTURE, RECEPTORS AND TRANSLOCATION ROUTES

All colicins show the same type of organization, coherent with their mechanism of action. The standard functional domain sequence of all colicin molecules is from N' (amino) to C' (carboxy) terminus. Their structure comprises three distinct domains: (A) a domain involved in recognition of specific receptors, (B) a domain involved in translocation, and (C) a domain responsible for their lethal activity, with a molecular mass of 30 to 70 kDa (5,50).

To exert their action, colicins must cross a physical barrier, the outer membrane with lipopolysaccharide molecules on the outer surface of its bilayer and its small pores, and be taken up by the sensitive cells (5). Thus, the colicins developed a mechanism of parasitism of multiprotein system used by sensitive cell for important biological functions. These proteins include porins (OmpF, OmpA and OmpC), vitamin B12 (BtuB), siderophore and nucleoside (Tsx) receptors, (Table. 1) as well as the multiprotein systems that contribute these proteins (49).

Two different but homologous translocation systems have been described, the Ton and the Tol systems (


MECHANISM OF ACTION

Colicins kill sensitive bacteria in three main and distinct ways (Fig. 2). The most frequent mechanism is the formation of ion channels in the plasma membrane (pore formation), resulting in membrane depolarization (5,98). The opening of the pore also induces a phosphate and sometimes K+ efflux, which leads to depletion of cytoplasmic ATP (50). Less frequent is the nuclease activity of colicins, which can be directed against the chromosomal DNA (acting as a nonspecific DNA endonuclease) or a specific endonuclease against 16S-rRNA. The least frequent is degradation, catalyzing the hydrolisis of the b-1,4 bond between N-acetyl glucosamine and N-acetylmuramic acid in the glycan backbone of the bacterial cell wall or inhibition of synthesis of wall peptidoglycan or murein inducing the formation of spheroplasts and consequently, cell lysis (47,98). Interestingly, the mechanism of inhibition of murein synthesis and hydrolysis is quite similar to betalactamic antibiotics and lisozyme action.


The mode of action of many colicins has not been clarified. However the colicin A (pore forming) and colicin E groups (nucleases) are the most thoroughly understood, as shown in


Figs. 3 and

4 , although the molecular events of translocation and final interaction with a particular cellular target are not known for most colicins (19,49).


GENETIC FEATURES, COLICIN SYNTHESIS, INDUCTION AND CELL DEATH

The synthesis of colicins is coded by genes on the so-called Col plasmids which may or may not be conjugative or even able to mobilize the transfer of genes encoding for antibiotic resistance and other genes encoding virulence factors of uropathogenic E.coli (16,32). The pCol plasmids vary widely in size, commonly from 6.6 Kb (pColE1) to 94 Kb (pColH); however plasmids smaller than 5.5 Kb and plasmids larger than 94 Kb have been detected (98).

The basic genetic structure of colicin consists of a gene cluster that carries at least two, usually three genes, the colicin structural gene (col or cea in the pColE1), followed by the gene (imm) for the structure of the immunity protein and finally the gene (kil) encodes for the lysis protein or bacteriocin release protein (BRP).

Colicin production is induced by DNA-damaging agents, or environmental factors such as increasing population density and nutrient depletion (65). E. coli cells containing the Col plasmid normally synthesize the bactericidal colicin at low levels, but exposure to DNA-damaging agents such as UV irradiation or mitomycin C induces high levels of synthesis (44). The factor responsible for this induction is the bacterial "SOS system of DNA repair" which causes RecA proteinase activation and consequent inactivation of Lex A protein, which is a repressor of many DNA repair genes and also of plasmid genes for colicin synthesis (56,99). Under standard, but unknown, conditions, colicin synthesis is switched off in most cells of the population; it occurs only in a small part of the population as a result of a random activation of the "SOS system of DNA repair" (98). Other mechanisms of colicin synthesis have been described such as nonspecific catabolic repression and mRNA regulation by "stringent response" (55,86).

Colicin release into extracellular medium requires the expression and activity of a so-called BRP or lysis protein (108).

The lytic protein is a small lipoprotein that activates the endogenous outer membrane phospholipase A which is important for the permeabilization of the cell envelope (lysis) and death of the producer bacteria (21). However, some colicin gene clusters do not contain a gene kil (lysis protein) and the mechanism by which these colicins reach extracellular environment is unclear.

IMMUNITY TO COLICINS

Colicinogenic bacteria are protected against colicin molecules they produce. This specific protection is provided by an immunity protein that interacts specifically with the C- terminus domain of the colicin protein, rendering it inactive (75). The immunity proteins that bind in the cytoplasm to the colicins with nucleasic activities such as E2 and E9 are released as an equimolar colicin-immunity protein complex into the extracellular medium. The immunity proteins of the colicins with pore-forming activity such as Ia and Ib are found and active in the cytoplasmic membrane, and these colicins are released without bound immunity proteins (12).

Expression of the immunity genes may or may not be subject to the "SOS system of DNA repair" control. The immunity genes with the same transcription polarity as the colicin genes are controlled by the "SOS system of DNA repair", whereas immunity genes transcribed in opposite orientation have their own, usually weak, promoter (10).

COLICIN ECOLOGY

From an ecological point of view, colicins are anticompetitor molecules (23). Although research on colicins has generated a wealth of information in terms of molecular genetics, mode of action and application, little is known about the natural ecology of colicins and the role it plays in the bacterial ecology (24). The production of substances that exhibit antimicrobial characteristics such as colicins is one of the numerous mechanisms that enable bacteria to respond to environmental challenges (11). It apparently plays a role in competitive interactions between members of a microbial community (82).

Although colicin production is widespread, colicins are assumed to be of greater significance in intra- rather than interspecies competitive interactions. This concept results from observations suggesting that a colicin produced by one species is usually not effective against strains from different species (28).

The best evidence for the ecological role of the colicins is the high frequency at which natural colicinogenic strains are encountered (75). The frequency of colicinogeny in E.coli strains is usually reported to be 24-45% (9). Little is known about the factors that determine the frequency of colicinogeny in natural populations (38,88). However, Pugsley (74) reported that more than 30% of lactose-fermenting gram-negative bacteria isolated from the River Seine produced one or more colicins, which were active against E. coli K12, a standard colicin indicator strain. Surprisingly, 98% of these strains were susceptible to classic antibiotics (76).

Studies suggest that colicinogeny is more frequent among pathogenic than commensal isolates and that it is more prevalent among humans isolates (50%) than animal isolates (16%) (80,109).

It seems unclear whether colicinogeny itself is an independent pathogenic factor or whether it is an associated marker of other virulence factors. However, several virulence factors including synthesis of aerobactin, alpha-haemolysin and P-fimbriae are known to be associated with some colicins and may account for this association (22,60,63).

The increased virulence of colicinogenic strains, in particular of those producing colicin V (has been now classified as a microcin V) might be due to these virulence determinants since colicin V itself does not seem to act as a pathogenic determinant, though a report has been shown that colicin V is directly involved in pathogenesis. (63,111).

Recent data reported by Šmarda and Obdrzálek (94) showed that 41% of E. coli strains isolated from healthy humans in the Czech population produce colicins. The same incidence of colicinogenic producers has been found in the bowel of patients suffering of salmonelloses or malignant tumors of bowel. The incidence of haemolytic uropathogenic strains detected in these patients was only 22%, whereas and incidence of 48% was found in the bowel of patients with Crohn's disease and the highest incidence, 56%, was found in patients with ulcerative colitis.

POPULATION ANALYSIS

A number the theoretical models investigating the population dynamics of bacteriocin-producing bacteria have been described (15,28,51). These models assumed the existence of a cost-benefit ratio. (23,51). The sensitive cells are favored because they do not need to pay the cost associated with colicin production, i.e. the loss to the colicinogenic population due to colicin synthesis and subsequent cell lysis and the growth rate disadvantage resulting from the energetic costs imposed by colicin plasmid carriage (11). However, for the colicin-producing strain to invade a new habitat these cost must be exceeded by the advantage gained due to the fact that colicin production is determined by: the initial density of colicinogenic cells and by the rate at which sensitive cells are killed by the colicins, which in turn is determined by the amount of colicin released per lysed cell and by the rate at which colicin binds to sensitive cells (15,28,51,82).

Some studies have suggested that the dynamics of these competitive interactions differ in different cells habitats (15,81). It has been proposed that invasion of a sensitive population by a producer strain is predicted to be ineffective in a homogeneous, well-mixed medium, such as liquid culture, unless initial frequencies is high. This is due to the dilution of toxin in liquid culture and the cost of colicin production. On the other hand, it has been predicted that sensitive strains at low initial frequencies will not invade a colicin-producing population in a liquid culture due to the high levels of toxin present (62,79). However, if there is a structure of the environment, such as a solid surface, and there is spatial heterogeneity in resource abundance, then a stable polymorphism of producer and sensitive strains can exist. In summary, sensitive strains will persist in poor habitats where the rate of resource competition is high, while producing strains will persist in rich habitats where resource competition is low and where they can take advantage of rich nutrient and energy sources for colicin production (28).

COLICINS EVOLUTION

Due to the large amount of information available, the colicins have served as a model to investigate the mechanism of evolution and diversification of bacteriocins (26,83,103). Most of these studies has involved comparisons of DNA and protein sequences among colicin, immunity, and lysis genes, and encoded proteins to infer evolutionary relationship and molecular mechanism of diversification (79).

Riley (77) distinguished five classes of colicin proteins based on sequence comparisons. In the cited study she found a high similarity within class, except for colicin B, which shows similarities with colicin D (Fredericq, personal communication). The most interesting inference from the phylogenetic data of colicin protein is that this class of proteins represents a highly heterogeneous group (78).

Tan and Riley, (102) propose two different hypothetical models to explain the evolutive diversification of the colicins: positive selection and recombination.

The role of positive selection in colicin evolution has been proposed to explain an unusual pattern of divergence between two pairs of gene clusters (E3/E6 and E2/E9- nucleases). Comparisons of DNA sequence showed an apparent excess of synonymous substitutions (which alter a codon but not alter the specific amino acid) and nonsynonymous substitutions (which alter a codon as well as the specific amino acid) in the immunity portion, the immunity gene and the immunity binding region of the colicin gene.

To elucidate this phenomenon, a process of diversification was proposed. First of all, a point mutation occurs in the immunity gene of a colicin that confers a broadened immunity function. Those cells are immune to themselves, to their immediate ancestors, and to several other colicins (Fig. 5.1). This evolved colicin gene cluster will have an advantage over its ancestor in the presence of colicin and will be selectively retained in the population. Then, a second mutation may occur in the evolved colicin gene, resulting in a gene cluster that has a colicin to which its ancestor is no longer immune (Fig. 5.2).



A strain carrying this evolved colicin gene cluster will have a large and selective advantage. Hence, positive selection will drive this 'super killer' rapidly into the population, and repeated rounds of this form of diversification of immunity function will result in the accumulation of synonymous and nonsynonymous substitutions in the immunity portion (79).

In this case, positive selection can act to produce more and more diversity. Thus, the mechanism of 'super killer' appearance could be contributing to the enormous variation in E. coli DNA (5%)- the highest diversity to be expected in a single species (58).

The second model, recombination, could explain why within pore-forming colicins the protein sequence similarity is low, rarely exceeding 40%. Some findings have shown that in this group of colicins regions of the colicin gene sequence encoding rather precise functional domains have recombined to give rise to new colicins. Such recombination events occur between and within the groups of pore-forming colicins (79). Comparisons of DNA and protein sequence similarity of this colicin group have shown that they represent a highly divergent class of proteins and that they share a common ancestor. Thus, the process of diversification of pore-forming colicins is the result of numerous recombination events that play a role in selecting random functional domains of these colicins and generating novel types of colicins (80).

COLICIN RESISTANCE

There are two primary mechanisms that result in insensitivity of E.coli cells to the action of colicins, aside from the immunity mechanisms of the colicinogenic host: (a) resistance that evolved as an alteration by mutation or absence of a colicin receptor, and (b) tolerance that is related to absence of a functional colicin translocation system (20,31,91,110,112).

Gordon et al. (33) revealed that more than 70% of natural isolates of E. coli were resistant to at least one colicin and 30% of the isolates were resistant to three or more colicins. Loss of the receptor can confer resistance to all colicins that recognize a certain receptor. However, other receptor mutations have been described that provide specific resistance to a single colicin or a subset of colicins (10,44,71).

It should be pointed out that the sensitivity of strains observed under natural conditions may change under in vitro conditions.

ACTION OF COLICINS ON EUKARYOTIC CELLS

Studies on the action of colicins on eukaryotic cells has been done since the 70's. Farkas-Himsley and Cheung (25) reported toxic effects of several bacteriocins produced by gram-negative bacteria, including colicins, on various eukaryotic cells. Šmarda et al. (95) detected inhibition of mouse fibroblasts L and human epithelial HeLa cells by colicin E3.

Saito and Watanabe (85) reported toxic effects of a colicin on the established mouse neoplastic L60T line. Many attempts were made to prove inhibitory effects of bacteriocins on mammalian cells, including tumor cells (92).

Standard cells were shown to be less sensitive to colicins than tumor-transformed ones and malignant animal cells were more sensitive than human cells. Šmarda et al. (95) and Šmarda (92) described the inhibitory effects of colicins on eukaryotic cells in culture and also in vivo. In the first of these studies, several degrees of activity of a colicin towards various cells were found to be common, as later observed by others (54).

Recent reports, (94) showed that both colicins E1 and E3 were cytotoxic to oncogene v-myb-transformed chicken monoblasts. Chumchalova and Šmarda (personal communication) reported that colicins E1 and especially A inhibited 11 human tumor cell lines carrying determined mutations of the p53 gene, while the parallel inhibition of a standard human fibroblast line was very low. The effect was cytotoxic. In the same systems, colicins E3 and U were shown to be ineffective. In addition, Oravec and Šmarda (personal communication) studied the effects of colicin E3 on solid HK-adenocarcinoma of mice in vivo. Tiny doses injected daily directly into subcutaneous nodes of the tumor reduced tumor weight by 61%. Colicin E2 and A dramatically decreased the viability of three murine lymphoma cells lines by 40-58 %. Colicin A treatment of mice with transplanted LP-2 plasmocytoma prolonged their survival by 43 %.

PRACTICAL APPLICATIONS OF COLICINS AND PERSPECTIVES

A number of practical applications of colicins have been suggested, especially due to their antimicrobial properties. Different biological problems can be addressed using the colicin system (44). Interest in natural products rather than man-made chemicals should lead to further opportunities for the use of colicins in areas such as the control of plant diseases of bacterial origin, and even in medical applications as preparations of colicinogenic E.coli strains commercially available under the names of MUTAFLORâ and SYMBIOFLORâwhich have proved to be successful in the treatment of idiopathic chronic constipation as well as functional intestinal disorders and chronic inflammatory bowel disease (45,52,53). In addition, a promising field in biotechnology is the use of bacteriocin release proteins (BRP) or lysis proteins mediating the release of a wide variety of heterologous proteins. Since expression of BRP causes the release of almost the entire periplasmic content, expression and processing of the target protein should be highly efficient to selectively enrich the culture medium with the target protein (100,108). The last, but most hopeful example, is the antitumor effect of colicins that was confirmed in vitro as well as in vivo. In the future, colicins could be used against certain types of tumor such as lymphosarcoma, breast carcinoma and different colon tumors (91,92,95,96).

CONCLUSIONS

The start of colicin research was not motivated by any concrete needs (34). The colicins were and are studied simply because they exist (98). They represent a special and highly successful adaptation form of environment challenge and an important source of data for the understanding of bacterial relationships, their evolution and diversity. Studies about colicins were and still are promising not only because of their possible applications, but especially to discover how complex and wonderful the bacterial universe is.

Submitted: August 20, 2001; Returned to authors for corrections: January 08, 2002; Approved: July 26, 2002

  • 1. Abbot, J.D.; Graham, J.M. Colicin typing of Shigella sonnei Moth. Bull. Minist. Health Lab. Serv, 20: 50-51, 1961.
  • 2. Ahmer, B.M.M.; Thomas, M.G.; Larsen, R.A.; Postle, K. Characterization of the exbBD operon of Escherichia coli and role of ExbB and ExbD in TonB function and stability. J. Bacteriol, 177: 4742-4747, 1995.
  • 3. Akutsu, A.; Masaki, H.; Ohta, T. Molecular structure and immunity specficity of colicin E6, an evolutionary intermediate between E-group colicins and cloacin DF13. J. Bacteriol, 171: 6430-6436, 1989.
  • 4. Baba, T.; Chneewind, O. Instruments of microbial warfare, bacteriocin synthesis, toxicity and immunity. Trends in Microbiol, 6: 66-71, 1998.
  • 5. Bénédetti, H.; Frenette, M.; Baty, D.; Knibiehler, M.; Pattus, F.; Lazdunski, J.C. Individual domains of colicins confer specificity in colicin uptake, in pore-properties and in immunity requirements. J. Mol. Biol., 217: 429-439, 1991.
  • 6. Ben-Gurion, R.; Hertman, I. Bacteriocin-like material produced by Pasteurella pestis J. Gen. Microbiol., 19: 289-294, 1958.
  • 7. Bradley, D.E. Colicins G and H and their host strains. Can J. Microbiol., 37: 751-757, 1991.
  • 8. Bradley, D.E.; Howard, S.P. A new colicin that adsorbs to the outer membrane protein Tsx but is dependent on the TonB instead of the TolQ membrane transport system. J. Gen. Microbiol., 138: 2721-2724, 1992.
  • 9. Brandis, H.; marda, J. Bacteriocine und bacteriocinnähnliche Substanzen Gustav Fisher Verlag, Jena, 1971.
  • 10. Braun, V.; Pilsl, H.; Grob, P. Colicin structures, modes of action, transfer through membranes, and evolution. Arch. Microbiol., 161: 199-206, 1994.
  • 11. Campbell, A. Evolutionary significance of accessory DNA elements in bacteria. Ann. Rev. Microbiol., 35: 55-83, 1981.
  • 12. Cavard, D.; Oudega, B. General introduction to the secretion of bacteriocins. In: James, R., Lazdunski, C.; Pattus, F. (eds). Bacteriocins, Microcins and Lantibiotics Springer-Verlag, Berlin, 1992, pp.297-305.
  • 13. Chak, K.F.; Kuo, W.S.; Lu, F.M.; James, R. Cloning and characterization of the ColE7 plasmid. J. Gen. Microbiol., 137: 91-100, 1991.
  • 14. Chan, P.T.; Ohmori, H.; Tomizawa, J.; Lebowitz, J. Nucleotide sequence and gene organization of ColE1 DNA. J. Biol. Chem., 260: 8925-8935, 1985.
  • 15. Chao, L.; Levin, B.R. Structured habitats and evolution of anticompetidor toxins in bacteria. Proc. Natl. Acad. Sci. USA, 78: 6324-6328, 1981.
  • 16. Clowes, R.C. Colicin factors and epissomes. Genet. Res. Cambr., 4: 162-165, 1963.
  • 17. Cole, S.T.; Saint-Joanis, B.; Pugsley, A. P. Molecular characterization of colicinE2 operon and identification of its proteins. Mol. Gen. Genet, 198: 465-472, 1985.
  • 18. Cooper, P.C.; James, R. Two new E-colicins, E8 and E9 produced by a strain of Escherichia coli. J. Gen. Microbiol., 130: 209-215, 1984.
  • 19. Cramer, W.A.; Lindeberg, M.; Taylor, R. The best offense is a good defense. Nat. Struct Biol, 6: 295-297, 1999.
  • 20. Davies, J.K.; Reeves, P. Genetics of resistance to colicins in Escherichia coli K-12: cross- resistance among colicins of group B. J. Bacteriol., 123: 96-101, 1975.
  • 21. Dekker, N.; Tommassen, J.; Verheij, H.M. Bacteriocin release protein triggers dimerization of outer membrane phospholipase A in vivo. J. Bacteriol, 181: 3281-3283, 1999.
  • 22. Dobrindt, U.; Blum-Oehler, G.; Hartsch, T.; Gottschalk G.; Ron, Z.E.; Fünfstück, R.; Hacker, J.S.-fimbria-encoding determinant sfai is located on pathogenicity island III 536 of uropathogenic Escherichia coli strain 536. Infect. Immun, 69: 42484256, 2001.
  • 23. Dykes, G.A. Bacteriocins: ecological and evolutionary significance. Trends Ecol. Evol., 8: 369-386, 1995.
  • 24. Dykes, G.A.; Hastings, J.W. Selection and fitness in bacteriocin-producing bacteria. Proc. R. Soc. Lond B. Biol. Sci, 264: 683-687, 1997.
  • 25. Farkas-Himsley H.; Cheung R. Bacterial proteinaceous products (bacteriocins) as cytotoxic agents of neoplasia. Cancer Res, 36: 3561-3567, 1976.
  • 26. Feldgarden M.; Golden, S.; Wilson, H.; Riley, M. A. Can phage defense maintain colicin plasmids in Escherichia coli? J. Microbiol., 141: 2977-2984, 1995.
  • 27. Foulds, J.; Shemin, D. Properties and characteristics of a bacteriocin produced by Serratia marcescens J. Bacteriol, 99: 655-660, 1969.
  • 28. Frank, S. Spatial polymorphism of bacteriocins and other allelopathic traits. Evol. Ecol, 8: 369-386, 1994.
  • 29. Fredericq, P. Acquisition de proprietes antibiotiques nouvelles par la souche E. Coli V sous l'action des bacteriophages T1, T5 et T7. Antonie van Leeuwenhoek J. Microbiol. Serol., 17: 102-106, 1951.
  • 30. Fredericq, P. Actions antibiotiques réciproques chez les Enterobacteriaceae. Rev. Belge Path. Exp. Med. exp, 19: 1-107, 1948.
  • 31. Fredericq, P. Genetics of two different mechanisms of resistance to colicins: resistance by loss of specific receptor and immunity by transfer of colicinogenic factors. Presented at Ciba Symp. Drug Resist. Microorg., Churchill, London, 1957.
  • 32. Fredericq, P.; Betz-Bareau, M. Transfert génétique de la proprieté colicinogéne chez E. coli. Compt. Rend. Soc. Biol., 147: 1110-1112, 1953.
  • 33. Gordon, D.M.; Riley M.A.; Pinou, T. Temporal changes in the frequency of colicinogeny in Escherichia coli from house mice. Microbiology., 144: 2233-2240, 1998.
  • 34. Gratia, A. Sur un remarquable exemple d'antagonisme entre deux souches de colibacille. Comp. Rend. Soc. Biol, 93: 1040-1041, 1925.
  • 35. Guasch, J.F.; Enfedaque, E.; Ferrer, S.; Gargallo, D.; Regué, M. Bacteriocin 28b, a chromosomally encoded bacteriocin produced by most Serratia marcescens biotypes Res. microbiol., 146: 447-483, 1995.
  • 36. Hamon, Y.; Péron, Y. A propos de quelques noveaux types de colicines thermostables. Compt. Rend. Acad. Sci, 258: 3121-3124, 1964a.
  • 37. Hamon, Y.; Péron, Y. description de sept noveaux types de colicines. État actuel de la classification de ces antibiotiques. Ann. Inst. Pausteur., 106: 44-54, 1964b.
  • 38. Hardy, K. Colicinogeny and related phenomena. Bacteriol. Rev., 39: 464-515, 1974.
  • 39. Hauduroy, P.; Papavassiliou, J. Identification of a new type of coline (colicine L) Nature., 195: 730-732, 1962.
  • 40. Horák, V. Two colicins from Shigellae. Fol. Microbiol., 35: 469-470, 1990.
  • 41. Hwang, J.; Manuvakhova, M.; Tai P.C. Characterization of in-frame proteins encoded by Cvaa,an essential gene in the colicin V secretion system: CvaA*stabilizes CvaA to enhance secretion. J. Bacteriol, 179: 689696, 1997.
  • 42. James, K.S.; Zinder, N. Highly purified colicin E3 contains immunity protein. Proc. Natl. Acad. Sci. USA, 71: 3380-3384, 1974.
  • 43. James, R.; Jarvis, M.; Braker, D.F. Nucleotide sequence of the immunity and lysis region on the ColE9-J plasmid. J. Gen. Microbiol, 133: 1553-1562, 1987.
  • 44. James, R.; Kleanthous, C.; Moore, G.R. The biology of E colicins: paradigms and paradoxes. Microbiology., 142: 1569-1580, 1996.
  • 45. Jansen, G.J.; Wildeboer-Veloo, A.C.; van der Waaij, D.; Degener, J.E. Escherichia coli as a probiotic? Infection., 26: 232-233, 1998.
  • 46. Koninsky, J.; Richards, F.M. Characterization of the colicin Ia and Ib. Purification and some physical properties. J. Biol. Chem, 245: 2972-2978, 1970.
  • 47. Konisky, J. Colicins and others bacteriocins with established modes of action. Ann. Rev. Microbiol., 36: 125-144, 1982.
  • 48. Lau, P.C.K.; Condie, J.A. Nucleotide sequences from the colicins E6 and E9 operons: presence of a degenerate transposon-like structure in the ColE9-J plasmid. Mol. Gen. Genet., 217: 269-277, 1989.
  • 49. Lazdunski, C.; Bouveret, E.; Rigal, A.; Journet, L.; Lloubès, R.; Bénédetti, H. Colicin import into Escherichia coli cells. J. Bacteriol., 180: 4993-5002, 1998.
  • 50. Lazdunski, C.; Bouveret, E.; Rigal, A.; Journet, L.; Lloubès, R.; Bénédetti, H. Colicin import into Escherichia coli cells requires the proximity of the inner membranes and others factors. Int. J. Med. Microbiol., 290: 337-344, 2000.
  • 51. Levin, B.R. Frequency-dependent selection in bacterial population. Phil. Trans. Roy Soc. Lond. B., 319: 459-472, 1988.
  • 52. Lodinova-Zadnikova, R.; Sonnenborn U.; Tlaskalova, H. Probiotics and E. coli infections in man., Vet Q, 20: 78-81, 1998.
  • 53. Lodinova-Zadnikova, R.; Sonnenborn, U. Effect of preventive administration of a nonpathogenic Escherichia coli strain on the colonization of the intestine with microbial pathogens in newborn infants. Biol. Neonate., 71: 224-232, 1997.
  • 54. Lokaj, J.; marda, J.; Mach, J. Colicin E3 enhances the oxireductive active of guinea-pig leukocytes. Experientia., 38: 1352-1353, 1982.
  • 55. Lotz, W. Effect of guanosine tetraphosphate on in vitro protein synthesis directed by E1 and E3 colicinogenic factors. J. Bacteriol., 135: 707-712, 1978.
  • 56. Lu, F.M.; Chak, K.F. Two overlapping SOS boxes in ColE1 operon are responsible for the viability of cells harboring the Col plasmid. Mol. Gen. Genet., 251: 407-411, 1996.
  • 57. Males, B.M.; Stocker, B.A.D. Colicin E4, colicin E5, colicin E6 and colicin A and properties of btub+ colicinogenic transconjugants. J. Gen. Microbiol., 128: 95-106, 1982.
  • 58. Morell, V. Bacteria diversify through warfare. Science, 278: 575, 1997.
  • 59. Morlon, J.; Lloublés, R.; Varenne, S.; Chartier, M.; Lazdunuski, C. Complex nucleotide sequence of the structural gene for the colicin A, a gene translated at a non-uniform rate. J. Mol. Biol., 170: 271-285, 1983.
  • 60. Moss, J.E.; Cardozo, T.J.; Zychlinsky, A.; Groisman, E.A. The selC-associated SHI-2 pathogenicity island of Shigella flexneri. Mol. Microbiol., 33: 74-83, 1999.
  • 61. Murinda, E.S.; Robert, R.F.; Evaluation of colicins for inhibitory activity against diarrheagenic Escherichia coli strains including serotype O157:H7. Appl. Environ Microbiol, 62: 3196-3202, 1996.
  • 62. Nakamaru, M. and Iwasa, Y. Competition by allelopathy proceeds in traveling waves: colicin-immune strain aids colicin-sensitive strain. Theor Popul Biol., 57: 131-144, 2000.
  • 63. O'Brien, G.J.; Chambers, S.T.; Peddie, B.H.; Mahanty, K. The association between colicinogenicity and pathogenesis among uropathogenic isolates of Escherichia coli Microb Pathog., 20: 185-190, 1996.
  • 64. Ölschläger, T.; Braun, V. Sequence, expression and localization of the immunity protein for colicin M. J. Bacteriol, 169: 4765-4769, 1987.
  • 65. Ozeki, E.T.; Stocker, H.; De Margerie, B.A.D. Production of colicin by single bacteria. Nature, 184: 337-339, 1959.
  • 66. Pilsl, H.; Braun, V. Novel colicin 10: assignment of four domains to TonB- and TolC-dependent uptake via the Tsx receptor and to pore formation. Mol. Microbiol, 16: 57-67, 1995a.
  • 67. Pilsl, H.; Braun, V. Evidence that the immunity protein inactivates colicin 5 immediately prior formation of the transmembrane channel. J. Bacteriol., 177: 6966-6972, 1995b.
  • 68. Pilsl, H.; Braun, V. Strong function-related homology between the pore-forming colicins K and 5. J. Bacteriol, 177: 6973-7, 1995c.
  • 69. Pilsl, H.; Killmann, H.; Hantke, K.; Braun, V. Periplasmic location of the pesticin immunity protein suggest sinactivation of pesticin in the periplasm J. Bacteriol, 178: 2431-2435, 1996.
  • 70. Postle, K. TonB protein and energy transduction between membranes. J. Bioenerg. Biomembr, 25: 591-601, 1993.
  • 71. Pugsley, A.P. Escherichia coli K12 strains for use in the identification and characterization of colicins. J. Gen. Microbiol., 131: 369-76, 1985.
  • 72. Pugsley, A.P. Nucleotide sequencing of the structural gene for colicin N. reveals homology between the catalytic C-terminal domains of colicin A and colicin N. Mol. Microbiol., 1: 317-325, 1987.
  • 73. Pugsley, A.P. The immunity and lysis genes of CoIN plasmid pCHAP4. Mol. Gen. Genet., 211: 335-341, 1988.
  • 74. Pugsley, A.P. The ins and outs of colicins. Part I. Production, and translocation across membranes. Microbiol. Sciences, 1: 168-176, 1984a.
  • 75. Pugsley, A.P. The ins and outs of colicins. Part II. Lethal action, immunity and ecological implications. Microbiol. Sciences, 1: 203-205, 1984b.
  • 76. Pugsley, A.P.; Schwartz, M. Colicin E2 release: lysis, leakage or secretion? Possible role of a phospholipase. EMBO J., 10: 2393-2397, 1984.
  • 77. Riley, M.A. Molecular evolution of colicin. Mol. Biol. Evol, 10: 1048-1059, 1993a.
  • 78. Riley, M.A. Molecular mechanisms of colicin evolution. Mol. Biol. Evol., 6: 1380-1395, 1993b.
  • 79. Riley, M.A. Molecular mechanisms of bacteriocin evolution. Ann. Rev. Microbiol., 32: 255-278, 1998.
  • 80. Riley, M.A.; Gordon, D.M. A survey of col plasmids in natural isolates of Escherichia coli and an investigation into stability of col-plasmids lineages. J. Gen. Microbiol., 138: 1345-1352, 1992.
  • 81. Riley, M.A.; Gordon, D.M. Ecology and evolution of bacteriocins. J. Ind. Microbiol., 17: 155-158, 1995.
  • 82. Riley, M.A.; Gordon, D.M. The ecology and evolution of bacteriocins. J. Ind. Microbiol., 17: 151-158, 1996.
  • 83. Riley, M.A.; Tan Y.; Wang, J. Nucleotide polymorphism in colicin E1 and Ia plasmid from natural isolates of Escherichia coli. Proc. Natl. Acad. Sci. USA, 91: 11276-11280, 1994.
  • 84. Roos, U.; Harkness, R.E.; Braun, V. Assembly of colicin genes from a few DNA fragments. Nucleotide sequency of colicin D. Mol. Microbiol., 3: 891-902, 1989.
  • 85. Saito, H.; Watanabe, T. Effect of a bacteriocin produced by Mycobacterium smegmatis on growth of cultured tumor and normal cells. Cancer Res, 39: 5114-5117, 1979.
  • 86. Salles, B.; Weisemann, J.M.; Weinstock, G.M. Temporal control of colicin E1 induction. J. Bacteriol., 169: 5028-5034, 1987.
  • 87. Schramm, E.; Mende J.; Braun, V.; Kamp, R.M. Nucleotide sequence of colicin B activity gene cba: consensus peptapeptide among TonB-dependent colicins and receptors. J. Bacteriol., 169: 3350-3357, 1987.
  • 88. Selander, R.K.; Musser, J.M.; Caugant, D.A.; Gilmour, M.N.; Whittam, T.S. Population of genetics pathogenic bacteria. Microb. Pathog., 3: 1-7, 1987.
  • 89. majs, D. The morphology of bacterial cell in inhibition zones produced by colicins. Scripta Med, 68: 171-180, 1995.
  • 90. majs, D.; Pilsl, H.; Braun, V. Colicin U a novel colicin produced by Shigella boydii J. Bacteriol., 179: 4919-4928, 1997.
  • 91. marda, J. Resistance and tolerance of bacteria to E colicins. In: James, R.; Lazdunski, C.; Pattus, F. (eds). Bacteriocins, Microcins and Lantibiotics Springer-Verlag, Berlin, 1992, pp.493-505.
  • 92. marda, J. The action of colicins on eucaryotic cells. J. Toxicol. Toxin. Rev, 2: 1-76, 1983.
  • 93. marda, J.; Obdrzálek, V. Colicin Q Zbl. Bakt. Hyg. A I Orig., 200: 111-118, 1966.
  • 94. marda, J.; Obdrzálek, V. Incidence of colicinogenic strains among human Escherichia coli. J. Basic Microbiol, 41: 367-374, 2001.
  • 95. marda, J.; Obdrzalek, V.; Taborsky, I.; Mach, J. The cytotoxic and cytocidal effect of colicin E3 on mammalian tissue cells. Fol. Microbiol., 23: 272-277, 1978.
  • 96. marda, J.; Oravec, C. In vitro and in vivo inhibition of blast lymphocytes by colicins. Fol. Microbiol., 38: 120-121, 1993.
  • 97. marda, J.; Petrzelová, J.; Vyskot, B. Colicin Js of Shigella sonnei: calssification of type colicin "7". Zbl. Bakt. Hyg. A I Orig., 263: 530-540, 1987.
  • 98. marda, J.; majs, D. Colicins: exocellular lethal proteins of Escherichia coli. Fol. Microbiol., 43: 563-582, 1998.
  • 99. Spangler, R.; Zhang, S.; Krueger, J.; Zubay, G. Colicins synthesis and cell death. J. Bacteriol., 163: 167-173, 1985.
  • 100. Steidler, L.; Fiers, W.; Remaut, E.S. Efficient specific release of periplasmatic proteins from Escherichia coli using temperature induction of cloned kill gene of pMB9. Biotechnol. Bioeng., 44: 1074-1082, 1994.
  • 101. Stouthamer, A.H.; Tietze, G.A. Bacteriocin production by members of the genus Klebsiella. Antonie van Leeuwenhoek J. Microbiol. Serol., 32: 171-182, 1966.
  • 102. Tan, Y.; Riley, M.A. Nucleotide polymorphism in colicin E2 gene clusters; evidence for nonneutral evoultion. Mol. Biol. Evol, 14: 666-673, 1997.
  • 103. Tan, Y.; Riley, M.A. Rapid invasion of colicinogenic bacteria with novel immunity function. Microbiology., 142: 2175-2180, 1995.
  • 104. Toba, M.; Masaki, H.; Otha,T. Colicin E8 a DNase which indicates an evolutionary relationship between colicins E2 and E3. J. Bacteriol., 170: 3237-3242, 1988.
  • 105. van den Elzen, P.J.M.; Walters, H.H.B.; Veltkamp, E.; Nijkamp, H.J. Molecular structure and function of the bacteriocin gene and bacteriocin protein of the plasmid cloDF13. Nucl. Acids Res, 11: 2465-2477, 1983.
  • 106. Vianney, A.; Lewin, T.M.; Beyer Jr., W.F.; Lazzaroni, J.C.; Portalier, R.; Webster, R.E. Membrane topology and mutational analysis of the TolQ protein of Escherichia coli required for the uptake of macromolecules and cell envelope integrity. J. Bacteriol., 176: 822-829, 1996.
  • 107. Viejo, M.B.; Gargallo, D.; Ferrer, S.; Enfedaque, J.; Regué, M. Colining and DNA sequence analysis of a bacteriocin gene from Serratia marcescens. J. Gen. Microbiol, 138: 1737-1743, 1992.
  • 108. Wan Der Wal, F.; Luirink, J.; Oudega, B. Bacteriocin release proteins: mode of action, structure, and biotechnological application. FEMS Microbiol. Rev., 17: 381-399, 1995.
  • 109. Waters, V.L.; Croza, J.H. Colicins V virulence plasmid. Microbiol. Rev., 55: 437-450, 1991.
  • 110. Whelan, K.F.; Colleran E.; Taylor, D.E. Phage inhibition, colicin resistance, and tellurite resistance are encoded by a single cluster of genes on the IncH12 plasmid R478. J. Bacteriol., 177: 5016-5027, 1995.
  • 111. Wooley, R.E.; Nolan, L.K.; Brown J.; Gibbs, P.S.; Bounous, D.I.; Phenotypic expression of recombinant plasmids pKT107 and pHK11 in an avirulent avian Escherichia coli. Avian. Dis., 38: 127-34, 1994.
  • 112. Zinder, N.D. Resistance of colicins E1and K induced by infection of bacteriophage f1. Proc. Natl. Acad. Sci. USA, 70: 3160-3164, 1973.
  • Fig. 1). The Ton translocation system is formed by TonB and two other proteins, ExbB and ExbD, which are clustered on the
    E. coli chromosome (2,106). The components of the Tol translocation system are TolQ, TolR, TolA, TolB, and Pal and their genes are clustered also on the
    E. coli chromosome (70).
  • to
    Correspondence
    Av. Antônio Carlos, 6627
    Departamento de Biologia Geral - Instituto de Ciências Biológicas
    Universidade Federal de Minas Gerais
    31270-901, Belo Horizonte, MG, Brasil
    Fax: (+5531) 3499-2567
    E-mail:
  • Publication Dates

    • Publication in this collection
      23 June 2003
    • Date of issue
      Sept 2002

    History

    • Accepted
      26 July 2002
    • Reviewed
      08 Jan 2002
    • Received
      20 Aug 2001
    Sociedade Brasileira de Microbiologia USP - ICB III - Dep. de Microbiologia, Sociedade Brasileira de Microbiologia, Av. Prof. Lineu Prestes, 2415, Cidade Universitária, 05508-900 São Paulo, SP - Brasil, Ramal USP 7979, Tel. / Fax: (55 11) 3813-9647 ou 3037-7095 - São Paulo - SP - Brazil
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