Antibiotics are widely used medicines for controlling
diseases both for us and our food. Nowadays, studies worldwide show problems
concerning a higher number of pathogenic bacteria strains becoming resistant, increasing
health risks. We have high dependency on aquaculture, it is the fastest-growing
food-producing business. However, it costs around several billion US$ per year to
prevent disease outbreaks and denature those already occurring. Resistant
pathogen studies are important in determining how resistance spreads. Defoirdt et al., (2011) states resistance genes,
transferable plasmids and integrons are passed via horizontal gene transfer to
bacteria, causing diseases such as Salmonella and Cholera. These studies are
also important as diseases limit aquaculture development. As a high abundance
of untreatable, harmful bacteria grow in waters around shoals, are consequently
ingested by fish, they then become treatable. In the absence of diseases
antibiotics are still used, causing resistance. Thailand’s 76 shrimp farms received
daily doses of 10 antibiotics.
This is an easy to follow review paper detailing other
methods, currently tested, for potentially replacing antibiotics. However,
methods were not written but referenced other studies, this could have enhanced
my understanding. Novel biocontrol strategies have reported success in certain
fish and shrimp species, preventing disease. Defoirdt et al , (2011) critically details benefits and constraints of each
technique.
1)
Killing
one specific pathogen. Using antibacterial agents, bacteriophages specific to
infecting target strains, results in decreased resistance and beneficial
bacteria harm. Shivu isolated strain-specific phages from shrimp hatcheries and
V. harveyi strains, he found lysed phages
could not infect other Vibrio sp. Therefore,
tiger shrimps (P. mondon) survival
increased from 17-86%. However, virulence genes can transfer resistance to
phage attachment. Vibrionaceae
genomes contain rctB homologues, a
perfect target for RctB to inhibit virulence gene replication.
2)
Growth
inhibitors. Using short-chain fatty acids in animal diets controls Salmonella and Vibrio’s growth by
decreasing intestinal pH, thus, increasing useful microbial communities. One
limitation is excess leaching, therefore, high doses are needed. Recently, polyhydroxyalkanoates
are added to gastrointestinal tracts producing similar effects, once degraded,
to short-chain fatty acids, increasing survival rate.
3)
Inhibition
of virulence gene expression. Beneficial as pathogen’s rate of developing
resistance is extremely low, however, there is environmental selective
pressure. Quarom sensing has two systems in Vibrio’s,
first; use N-acylhomoserine lactones
(AHLs) as signal molecules in the cytoplasm of Gram-negative bacteria. The
second; multi-channel quorum sensing at the cell surface. Both systems regulate
virulence gene expression, therefore, interfering with signal molecule
detection is a focus. In turbot, lactonase enzymes in Bacillus sp inactivate AHLs. Halogenated furanones also disrupt gene expression preventing
vibriosis. Reports however, show it is toxic in slightly higher concentrations than
when effective, therefore, a food additive cinnamaldehyde is used. Other quarom
sensing inhibiting compounds are produced by algae, corals, sponges, epidiotic
bacteria and marine bacterial secondary metabolites. Antivirulence therapy also
inhibit specific virulence factors. The cholera toxin in V. chloerae is controlled by the ToxR regulon, expression correlating
to its harmfulness, reports of virstatin inhibits gene expression, yet, untested.
This review, in my opinion,
suggests antibiotics are becoming outdated. Further work is needed regarding
combining new biocontrol strategies for disease prevention, as resistance
development still occurs individually. This paper mainly focusses on shrimp aquaculture,
including a wider range of species would have benefitted. Therefore, future aquaculture
research on farmed species would aid disease prevention. Better or more
biocontrol strategies could result, be combined, reducing antibiotic addiction.
My knowledge was limited on aquaculture. Thus, novel biocontrol strategies,
plus learning the molecular agents are obtained from aquatic organisms, attracted
my interest as they link to modern day human medicinal research and species
evolution.
Reference
Defoirdt, T., Sorgeloos, P., &
Bossier, P. (2011). Alternatives to antibiotics for the control of bacterial
disease in aquaculture. Current Opinion
in Microbiology, 14(3), 251-258
Hi Sophie,
ReplyDeleteThank you for your interesting summary of the review. I have a couple of questions:
- When using short chain fatty acids in feeds as bacterial growth inhibitors, is a reduction in fitness seen in the animals? In case it is, this could potentially represent a problem with implementing this strategy.
- Could using quorum sensing-disrupting strategies potentially affect signalling in beneficial bacteria, such as many of those associated with the hosts' gut? If so, has anyone investigated the effect of this on fitness?
Using antibiotics to control bacterial diseases in aquaculture nowadays is certainly unethical, and it is clear that new strategies need to be implemented. However, the economic benefit of employing a any new method must offset the cost of devising and implementing it: do the authors mention whether the three mentioned ways of controlling bacterial disease are economically "sound"?
Apologies for the many questions, I do think this is an interesting and crucial area where research funding should be spent on.
Thanks,
Alessandro
Hi Alessandro,
DeleteThose are very good questions and I will try my hardest to answer them.
These methods are still in practice for the marine world but are more advanced in terrestrial methods.
This paper did not state that there was a reduction in fitness of the animals, but rather that it increased the survival rate of those individuals. However, one of the studies they looked at (Defoirdt., et al (2006)) did state that by feeding a higher quality diet, that included the short-chain fatty acids, increased the energy in the Artemia Franciscan when they treated it to inhibit the growth of Vibrio campbellii. The was all this study stated on the matter and in my view it would suggest due to the increased energy that fitness was not reduced. However, there are few-no studies that I could find, most were about general quality of diets and polyunsaturated fatty acids affecting growth, that investigated this and so it would be a very interesting thing to study for further investigation.
I also thought about this quorum sensing affecting beneficial bacteria. From my understanding by this paper, every bacteria has its own unique signal molecules for quorum sensing and as they show in turbot, therefore, you would have to specify gene coding or retrieve that particular compound to inhibit those specific molecules. You may need it from an algae or a coral or even another bacteria. By doing this I would presume that beneficial bacteria will not be affected, you are not altering the environmental conditions but that select species. Fitness would therefore not be affected. Please correct me if I am wrong about quorum sensing signal molecules being unique to each specific bacteria.
This paper is a review about those methods put into practice and have not entered into the aquaculture world to replace antibiotics as of such. There was no mention of value of these methods or talk about any economical factors or implications as they mainly focussed on the positives of actually using the techniques for the product. This however, is a very good point and would have provided further knowledge into whether these methods could actually be used in terms of cost. Maybe they would be too expensive for businesses to use and therefore they would not be able to revert from using antibiotics, which would enhance the problem and not solve it. Maybe we will find out in Dan Merifields second lecture on health and disease.
They were good questions and I agree, research funding would be good to allow for further development in reducing reliance of antibiotics and resistance within our food and us.
Thank you,
Sophie,
Here is the reference to the paper I mentioned above.
Defoirdt, T., Halet, D., Sorgeloos, P., Bossier, P., & Verstraete, W. (2006). Short- chain fatty acids protect gnotobiotic Artemia franciscana from pathogenic Vibrio campbellii. Aquaculture, 261, 804-808.
Hello Sophie,
DeleteThank you for your exhaustive reply.
Interesting point regarding short-chain fatty acids: the reason why I asked is that I would expect short-chain fatty acids to be less energy-rich than longer-chain ones, therefore potentially representing an issue for their incorporation in feeds.
As for the quorum sensing molecules, I think you are right: quorum sensing systems of the LuxI-LuxR type in Gram negative bacteria are species-specific, as they are used for intraspecific communication. However, there are other systems used in interspecific communication, which are less specific (see Federle & Bassler, 2003 for a review). The same paper describes broad-range AHL inhibitors, which would disrupt quorum sensing non-specifically, although it does not mention the compounds referred to in the article you summarised (halogenated furanones). It would certainly be interesting to study the effects of such compounds on the whole microbiome, rather than on single pathogens.
Federle, M. J. & Bassler, B. L. (2003) "Interspecies communication in bacteria". J Clin Invest, 112 (9). pp 1291-1299.
Hi Alessandro,
DeleteThank you for your informative reply. I agree with you on the short-chain fatty acids being suposedly less-energy rich but I cannot comment further on their use in feed apart from that are possibly easier to break down. Yes, studying the whole microbiome would be a future study that would increase understanding and knowledge of this topic.
Thank you,
Sophie
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