|Year : 2013 | Volume
| Issue : 6 | Page : 823-825
Bdellovibrio bacteriovorus : A future antimicrobial agent?
K Harini1, Vidya Ajila2, Shruthi Hegde2
1 Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University, Deralakatte, Mangalore, Karnataka, India
2 Department of Oral Medicine and Radiology, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University, Deralakatte, Mangalore, Karnataka, India
|Date of Submission||22-Feb-2013|
|Date of Acceptance||25-Aug-2013|
|Date of Web Publication||7-Jan-2014|
Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Nitte University, Deralakatte, Mangalore 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Bdellovibrio and like organisms (BALOs) are small, predatory, Deltaproteobacteria that prey on other Gram-negative pathogens. Many authors have unfolded the possible use of BALOs as biological control agents in environmental as well as medical microbiological settings. They are found strongly associated with natural biofilms and recent studies have shown that effective predation occurs in these naturally occurring bacterial communities. Periodontal infections could also be an interesting target for the application of BALOs as biological Gram-negative bacteria and therefore potentially susceptible to BALOs antimicrobial agents. This proposition is based on the fact that almost all periodontal pathogens are predation. Accordingly, this review aims to present the evolution toward applying Bdellovibrio bacteriovorus as an antibacterial agent to deal with oral infections, general medical conditions, environmental and industrial issues.
Keywords: Bdellovibrio bacteriovorus , periodontopathogens, predation
|How to cite this article:|
Harini K, Ajila V, Hegde S. Bdellovibrio bacteriovorus : A future antimicrobial agent?. J Indian Soc Periodontol 2013;17:823-5
| Introduction|| |
Predation is persistent at all levels of life, found in all walks of life and possibly in all environments. Predation between bacteria has been known for a long time.  One of the methods used by bacteria for predation is periplasmic invasion. The predator cell invades and grows within a specific compartment found in Gram-negative cells, the periplasm. For e.g., Bdellovibrio like organisms (BALOs). This group of predators is unique in the fact that the predator is a bacterium that is clearly a living organism, as opposed to viruses and phages and is smaller than the prey, in contrast with protists. BALOs are highly motile Proteobacteria that prey on other Gram-negative bacteria.
Periodontitis is an infectious disease primarily associated with Gram-negative periodontopathogens. Microorganisms frequently isolated from periodontal pockets are the Gram-negative bacteria Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, all which are strongly associated with various forms of periodontitis.  Studies have provided support that oral infections, specifically periodontitis, may confer independent risks for different systemic conditions such as osteoporosis, diabetes mellitus, pulmonary infections, pre-term low-weight births and cardiovascular diseases.  Therefore, the mitigation of oral infection is of broad clinical importance. The importance of bacteria in dental plaque and the key role of plaque in the causation of periodontal diseases are well-established. The complexity in removing dental plaque or biofilms by conventional therapies led researchers to examine other alternative methods for biofilm control, such as biological control agents. One biological agent that might be used to control pathogenic bacteria is the predatory prokaryotes from the genus Bdellovibrio.  Furthermore; BALOs are perhaps the best studied and characterized predators of bacteria field. Therefore, an effect of BALOs on periodontopathogens could be of great clinical relevance and as such, will be the focus of this article.
Bdellovibrio bacteriovorus, Gram-negative predatory bacteria, was discovered accidentally by Stolp and Petzold in 1962 while isolating bacteriophages of the phytopathogen Pseudomonas syringaepv Phaseolicola from soil suspension.  They were named B.bacteriovorus , the name describing the morphology and the supposed way of life of the bacteria; they were curved and seemed to stick to their prey and to absorb the prey cell content, reminiscent of a leech ("bdella"in Greek). Robert E. Buzzzchanan coined the term B.bacteriovorus.  Bdellovibrio are highly motile, flagellated, tiny measuring about 0.25 Χ 1.0 μm, Gram-negative Deltaproteobacteria.  There are three species of Bdellovibrio-B. bacteriovorus, B. stolpii and B. starrii. There are also atleast two unspeciated groups, Bdellovibriosp. strain and the marine Bdellovibrios.
| Balos and Periodontal Health|| |
Periodontal diseases are a group of diseases primarily caused due to bacterial infection. The elimination of these pathogens during the treatment will enhance the clinical response. However, research has shown that the elimination of periodontopathogens by mechanical periodontal therapy alone was not predictable.  Besides, treatment of periodontal diseases is complicated by a number of draw backs like growing resistance to antibiotics and inefficiency of antimicrobial agent to penetrate in dental biofilms.  With these drawbacks, it is time to consider other alternatives. Predatory therapy can therefore be regarded as an interesting opportunity for the development of an adjuvant to standard periodontal therapy. It has recently been suggested that BALOs specifically reduced levels of Gram-negative pathogens in the oral cavity. Major advantages of using BALs in the treatment of oral infection include:
- Resistance to favorable commensal periodontal microbiota to BALO predation
- Lack of bacterial resistance mechanism to predation
- Do not induce strong immunological response. 
These characteristic features of BALOs go extremely well with the necessities for an oral biological antimicrobial agent. One biologic feature of Bdellovibrio that distinguishes it from other bacteriophages is their ability to invade biofilms, penetrate deeply and effectively destroy them.  Dashiff and Kadouri  reported that B.bacteriovorus could eliminate biofilms developed on hydroxyapatite surfaces and it could also attack metabolically inactive biofilms in the presence of saliva. This biological feature of BALO will be of great significance in the future for its use as an oral antibacterial agent in mouthwashes, gargles, etc.
| Evidence of Effectiveness of Balos on Oral Pathogens|| |
Van Essche et al.  reported that strain B. bacteriovorus (HD100) could attack and significantly reduce A. actinomycetemcomitans ATCC43718. Scanning electron microscope imaging also showed that Bdellovibrio was capable of markedly reducing the biofilm biomass.
Schoeffield et al.  reported that B. bacteriovorus 109J failed to prey in an oxygen-limited environment, but other BALOs may adapt to prey under these conditions. 
Dashiff and Kadouri  demonstrated the susceptibility of oral pathogens to predation by B. bacteriovorus 109J in vitro. It was reported that B. bacteriovorus 109J had the ability to prey on all the serotypes of A. actinomycetemcomitans and Eikenella corrodens, but no predation was detected among P. gingivalis, P. intermedia, T. forsythia and F. nucleatum ATCC10953.
Van Essche et al.  evaluated the predation efficiency of six different BALO strains (B.bacteriovorusHD100, B. bacteriovorus109J, BacteriovorusBEP2, Bacteriovorax FCE, PeredibacterstarriiA3.12, BacteriovoraxstolpiiUki2) against six different perioodontopathogens (A. actinomycetemcomitans, E.corrodens , P. gingivalis, C.sputigena , P. intermedia, F. nucleatum). Among the six different strains of BALOs, B.bacteriovorusHD100 had the widest prey spectrum by decreasing the viability of four tested periodontopathogens. The other strains like B. bacteriovorus 109J caused lysis of three perioodontopathogens, Bacteriovorus BEP2 and Bacteriovorax FCE was effective two tested pathogens. P.starrii A3.12 was effective against A.actinomycetemcomitans . B.stolpii Uki2 did not predate any of the tested preybacteria. This highlights the concept that the predator - Prey interactions are highly BALO strain specific. 
Van Essche et al.  reported that F. nucleatum was the most susceptible prey, being preyed on by four of the six BALO strains.
A study done by MarkelovaNI  showed that another B.bacteriovorus strain, 100NCJB, could attack Helicobacterpylori.
| Other Therapeutic Uses|| |
Many authors reported the predatory efficiency of BALOs against Escherichia More Details coli in urinary tract infections, entero hemorrhagic E. coli in gastrointestinal infections and wound, burn and respiratory infections caused by Pseudomonasaeruginosa. 
BALOs also have wide applications in agricultural field, animal husbandry and food industry.
| Drawbacks|| |
- BALOs fail to completely kill their prey, even at high predator to prey ratios. However, resistance is due to a plastic phenotype rather than permanently genetically encoded  and to date, completely resistant mutant prey has not been isolated. The fact that the resistance to BALOs is lost quickly proposes that they utilize a cellular component necessary for survival of the prey and thus their predation
- Inability to attack Gram-negative bacteria with S-layer on their surfaces  and their activity is affected by the physiological status of their prey and by the presence of other bacteria, which may interfere and decrease or even increase their activity 
- These bacteria were found to be strict aerobes, restricting their potential use in oxygen-limited environments, such as gut, urinary tract or periodontal pockets
- BALOs activity is also reduced significantly in presence of some chemicals, such as high concentrations of glucose or glycerol and also at low pH.  These positive and negative interactions with the surrounding environment affect the efficiency of predation in real application. Meanwhile, one class of chemicals that was found to have no effect on BALOs was B-lactam antibiotics.  Consequently, BALOs can be used in conjunction with these antibiotics since the predatory strains will still be active and attack the prey species. This attribute is clearly beneficial with an antibiotic resistant strain.
| Conclusion|| |
The promising ability of BALOs strongly support the concept of using B.bacteriovorus for treatment of disease-related biofilms and particularly, periodontal infections. Its extensive applications offer an exciting path for further research where in vivo studies should be the focus of the future.
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