Europe to draft plan to encourage development of new antibioticsBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b5309 (Published 04 December 2009) Cite this as: BMJ 2009;339:b5309
All rapid responses
New antimicrobial agents are urgently needed to meet the challenges
posed by the re-emergence of infectious diseases1-4. The search for new
antibacterial compounds from novel natural sources is a vital research
area. Insects represent 80% of all fauna and the most widespread group
within the animal Kingdom. Furthermore, some of these organisms such as
cockroach live in the filthiest places known to man and thrive. Under
these unsanitary and unhygienic environments, they encounter different
types of bacteria, even superbugs. It is therefore logical that they have
developed ways of protecting themselves against micro-organisms. Thus our
hypothesis was that they must have a potent defence against superbugs.
Similarly, we were intrigued when we noticed that many soldiers were
returning from different parts of the world with unusual infections, yet
locusts living in the same areas were unperturbed and were thriving. How
do these creatures survive the onslaught of superbugs and ward off
disease. Their nervous system needs to be continuously protected because
if the nervous system goes down the insect dies. But they can suffer
damage to their peripheral structures without dying.
The aim of this study
was to investigate the potential antibacterial activity in various tissues
of the desert locust; Schistocerca gregaria and cockroach; Periplaneta
americana. Both insects were dissected to obtain muscle, fat body, ganglia
and haemolymph. Crude lysates were prepared from pooled insect tissue
samples and investigated for their antibacterial activity against Gram
positive (methicillin-resistant Staphylococcus aureus) and Gram negative
bacteria (neuropathogenic Escherichia coli K1). Crude extracts of insect
muscle, fat body and haemolymph produced no bactericidal effects. In
contrast, lysates of locust ganglia (head and thoracic) and cockroach
exhibited powerful antibiotic properties (>90% bactericidal effects)
against bacteria tested. The bactericidal effects were abrogated by
heating lysates to 100?C for 20 min suggesting the activity is
proteinaceous in nature. Antibacterial activity was retained in the
elutate after passing lysates through 10kDa size-exclusion spin columns.
Brain lysates had no cytotoxic effects on human brain microvascular
endothelial cells suggesting that the putative target/s is not present in
eukaryotic cells. By combining size-exclusion spin columns and Fast
Performance Liquid Chromatography, we have identified 8 different
molecules (3 - 10 kDa in molecular mass) in brain lysates that were toxic
to both MRSA and E. coli. Work is currently underway to further
characterize the antibacterial properties of insect brain lysates. It is
hoped that these molecules could eventually be developed into treatments
for bacterial infections that are increasingly resistant to current drugs.
These new antibiotics could potentially provide alternatives to currently
available drugs that may be effective but have serious and unwanted side
effects. Superbugs such as MRSA have developed resistance against the
chemotherapeutic artillery that we throw at them. They have shown the
ability to cause untreatable infections, and have become a major threat in
our fight against bacterial diseases. Thus, there is a continuous need to
find additional sources of novel antimicrobials to confront this menace.
To this end, insects such as cockroaches are one of the most ancient
organisms that have survived millions of years. They are one of the
hardiest insects that can survive without food for more than a month,
without air for >45min, can survive being submerged under water for
more than 45min, show high resistance to radiation, insecticides and
infectious diseases. We can learn a lot from them on how do they evolve
and protect themselves against superbugs as well as disease outbreaks,
some of which had the capacity to wipe off the human race from the face of
the Earth. Work is under way to identify the active ingredients, which
could ultimately result in the first antibiotics originating from insects.
1. WHO. Use of antimicrobials outside human medicine and resultant
antimicrobial resistance in humans. World Health Organization, 2002,
2. Goossens H, Ferech M, Vander Stichele R, Elseviers, M. Outpatient
antibiotic use in Europe and association with resistance: a cross-national
database study. Lancet 2005;365(9459):579-87.
3. Nordmann P, Naas T, Fortineau N, Poirel L. Superbugs in the coming
new decade; multidrug resistance and prospects for treatment of
Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa in
2010. Curr Opin Microbiol 2007;10(5):436-40.
4. Alanis AJ. Resistance to antibiotics: are we in the post-
antibiotic era? Arch Med Res 2005;36(6):697-705.
Contributors and sources: All authors contributed equally to the
manuscript and will act as guarantors.
Acknowledgement: The authors declare (1) no conflicts of interests for the
submitted work; (2) no financial relationships with commercial entities
that might have an interest in the submitted work; (3) no spouses,
partners, or children with relationships with commercial entities that
might have an interest in the submitted work; and (4) no non-financial
interests that may be relevant to the submitted work.
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Competing interests: No competing interests