From the archive, originally posted by: [ spectre ]


Anti-superbug weapon developed from wallaby milk

Wednesday, 9 May 2007  /  by Liz Williams
Cosmos Online

The tammar wallaby, found on islands off the south and west of
Australia, may have the power to treat superbugs in its milk.

This is one of a number of compounds recently found in marsupials,
such as koalas, that have exciting medical applications. Young
wallabies don’t develop an immune system until 100 days after birth,
yet they typically manage to avoid infection. This compound is part of
the reason why, say Australian scientists.

The compound, employs a unique mechanism to rapidly kill bacteria. And
it may work against some of the most dangerous multidrug-resistant
pathogens – such as vancomycin-resistant Enteroroccus, which poses a
particular threat to patients with compromised immune systems and

Rapid effect

Using advanced computer systems, researchers at the state of
Victoria’s Department of Primary Industries in Melbourne, Australia,
found more than 30 potential bug-fighting compounds in the milk of the
Tammar Wallaby (Macropus eugenii). One compound, known as AGG01, was
particularly potent said lead researcher and animal geneticist, Ben

Some experiments showed small amounts of a synthetic form of the drug
were able to kill all bacteria in 30 minutes. “We found in lab tests
that AGG01 is very effective against multidrug-resistant gram negative
bacteria, including those that are most difficult to treat,” he said.

The compound is termed a ‘broad-spectrum antimicrobial’ because it is
useful in the treatment of many bacterial and fungal pathogens.
Antimicrobial agents include antibiotics, as well as synthetically
devised compounds that can kill or prevent the growth of pathogens.
Broad spectrum antimicrobials, such as vancomycin, are typically used
as a last resort for treating infection, to reduce the chance of
bacteria becoming resistant, and also because they can have serious
side effects.

AGG01 is effective because it works rapidly and kills bacteria rather
than just preventing their growth, said Cocks. It also uses a novel
method to kill bacteria, which may involve striking at the bacterial
membrane, but more research is needed to confirm this.

Pouch secretions

“We know it is a unique mechanism, since it works against some
clinical isolates resistant to all available antibiotics,” he said.
“Theoretically, it is going to be hard for the bacteria to develop a
resistance [to AGG01], since the membrane is essential.”

Cocks is part of a team who presented a talk on the new compound this
week at the BIO2007 conference held in Boston, U.S..

The next step is to determine if the compound will be safe for use in
humans. Laboratory tests already indicate that it is not toxic to
human tissue, he said.

This is one of many compounds with exciting medical applications being
discovered in marsupial milk, commented Elizabeth Deane, a marsupial
immunologist at Macquarie University in Sydney. “Marsupials are born
after a very short gestation period and have no immune system of their
own, so a whole suite of maternal strategies are needed to protect the
young,” she said.

She added that maternal pouch secretions and skin secretions from the
newborn itself might also have antimicrobial properties. Deane herself
has found a number of antimicrobial compounds in koala pouch

Information about Wallaby Research I Wallaby Milk Antibacterial Press
Release I BIO2006 Wallaby Antimicrobial Abstract I Penicillin Found in
Wallaby Milk – News story from AAP

Wallabies: Our Disappearing Y chromosome, Premature Babies and Milk

Australia and the US National Institutes of Health are collaborating
in a multi-million dollar effort to sequence Skippy’s1 genome.

They’ve chosen the Tammar wallaby to represent kangaroo-kind. It’s
been the ‘model’ marsupial for many years and first made headlines in
the 1980s when an Australian team reported in Nature that the human
male Y chromosome was on the way out – based on their studies of
Tammar wallabies.

The Tammar wallaby is a small kangaroo which can do some clever things
that humans can’t.

For example:

A one day old joey (baby wallaby) weighs less than half a gram. It’s
roughly the equivalent of a 40 day old human embryo. But even with
immature lungs it can breathe unassisted, living in its mother’s
pouch. Melbourne researchers have visualised baby wallaby lungs using
a Japanese synchrotron and hope their research could help develop new
treatments for premature babies.

The baby’s development is driven by its mother’s milk. Each teat in
the pouch can produce a different formula. If a joey gets the wrong
milk it dies or grows up deformed. So dairy farmers are supporting
research into wallaby, seal and echidna milk to see what they can
learn about bioactive compounds in dairy milk.

Researchers have also discovered a novel antimicrobial protein in
wallaby milk and hope that it will lead to new mechanisms for tackling
antibiotic resistant bacteria.

These are some of the reasons that the Australian Genome Research
Facility has joined with the US National Institutes for Health to
sequence the genome of the wallaby – with the Victorian government
contributing A$4.5 million to the cost.

Why is the wallaby genome important?

The marsupial genome offers insights into the genetic programming of
all mammals – including humans. Because they are such distant
relatives in the mammalian family tree, they are sufficiently
different from humans that we can make useful comparisons which will
help us interpret the human genome.

When you find a gene in humans and kangaroos that has hardly changed
in 180 million years of evolution you know you are onto something
important to human development.

The wallaby genome initiative offers us the opportunity to exploit a
unique natural experiment. Wallabies and kangaroos show extraordinary
adaptability to environmental challenges. They have unique features of
lactation and reproduction that can help in the dairy industry, in
livestock fertility, and in human fertility and infertility.

An understanding of kangaroo reproduction will:

help us understand and manage human fertility and infertility
problems; and
help us understand and manipulate sex determination and other aspects
of fertility valuable to the livestock industries.

Studies have already revealed that the male Y chromosome in humans
used to be the same size as the female X chromosome 300 million years
ago. If the Y chromosome keeps losing genes it may disappear in the
distant future.

Who cares about wallaby milk?

Around the world people are looking for bioactive compounds in milk.

Bioactives are specific molecules that have useful, health-giving
properties. Bioactives found in milk include proteins, peptides,
lipids and carbohydrates. They could be used in the development of
medicines and functional foods – foods with components that provide a
specific health benefit.

Some bioactives already on the market are:

Lactoferrin, a minor component of the whey protein in milk, boosts
immune capacity in the digestive tract – lactoferrin is included in
baby foods and some yoghurts.

Travelan – colostrum product which improves strength and endurance in
athletes and improves immune strength against stomach ailments.

Recaldent – casein phosphopeptide – used in chewing gum and dental
products world wide to repair decayed teeth enamel.
Melbourne scientists are studying the mammary genes of the Australian
fur seal and the Tammar wallaby – mammals which have specific
lactation characteristics associated with bioactives in their milk.

In most mammals, the majority of the early growth and development
occurs inside the uterus with nutrients delivered via the placenta.

Marsupials, such as the Tammar wallaby, however, have only a very
brief pregnancy and give birth to a tiny, embryo-like young which then
matures inside the pouch. It seems that all the factors required for
growth of the young joey are found in the wallaby’s milk. The milk
changes composition as the joey develops to provide the appropriate
nutrition and the bioactives required for growth of the suckled young.
The very immature joey needs milk with a high colostrum level, as do
premature human babies. There are potential biomedical and veterinary
applications for these bioactives in treating premature babies.

Wallaby Antibiotics

Wallabies and kangaroos are born without an adaptive immune system and
don’t develop antibodies until over 100 days after birth. Yet somehow
the young in pouches manage to avoid infection.

Melbourne scientists have used a genomics approach to search for
factors in wallaby milk that might protect the young from bacteria in
wallaby milk. They’ve found a novel antimicrobial protein, AGG01, with
a broad-spectrum of antimicrobial activity. This may aid the pouch
young in adaptation to the environment and increase resistance to
potential pathogens. This finding may provide new mechanisms for
tackling antibiotic resistant pathogens.

Ben Cocks, Research Director
Animal Genetics and Genomics,
Department of Primary Industries Victorian
ben [dot] cocks [at] dpi [dot] vic [dot] gov [dot] au

Jane Whitley, Scientist
Animal Genetics and Genomics
Department of Primary Industries Victoria
jane [dot] whitley [at] dpi [dot] vic [dot] gov [dot] au

1 Skippy was the bush kangaroo that could do anything in an Australian
childrens’ TV series of the 1960s.

BIO2006 Wallaby Antimicrobial Abstract

A Potent Antimicrobial Protein Expressed in Wallaby Milk

We are investigating the potential of milk components to influence
mammalian development and health, and are using genomics approaches to
identify new bioactives for human use.

We are looking primarily at cows milk as a commercial source, but are
also using marsupial lactation since it can reveal evolutionally
conserved mechanisms in mammals, and because marsupials rely on milk
for extended periods of development. For example, the young of the
tammar wallaby are born immature after a short gestation period and
when born lack an adaptive immunesystem.

We used a bioinformatics approach to identify a number of immune and
anti-microbial componentsin our marsupial EST database.

This collection was derived from genes expressed in the wallaby
mammary gland at different stages of lactation and comprises a total
of 10,484 individual genes. We examined genes
expressed in mammary gland in the early stages of lactation and
identified a novel wallaby anti-microbial (AGG01) protein.

An orthologue to AGG01 is not present in other published mammalian
genomes, the most closely related genes being others found in the
wallaby genome. The existence of this marsupial specific gene is in
keeping with its expression in wallaby mammary gland during the early
phase of lactation, a phase of lactation that is not required in
eutherian mammals.

The genes for AGG01 and another anti-microbial proteins (eg lysozyme)
are up regulated in the mammary gland and show temporal variation in
gene expression at different phases of lactation.

Functional in vitro studies using synthetic AGG01 revealed potent anti-
microbial activity against gram-positive bacteria (eg Bacillus
subtilus, Streptococcus pyogenes) and gram-negative bacteria (eg E.
coli, Pseudomonas spp) and fungus (Candida albicans).

Thus, we have identified a novel antimicrobial protein, AGG01, with a
broad-spectrum of antimicrobial activity that is produced by the
lactating mammary gland.

The gene expression pattern of AGG01 and lysozyme in the mammary gland
throughout lactation suggest that there are two stages of increased
immune transfer in the tammar wallaby coinciding with the foetus
leaving the womb and the pouch young leaving the pouch. These may aid
the pouch young in adaptation to the environment and increase
resistance to potential pathogens.

The finding may provide new mechanisms for tackling antibiotic
resistant pathogens.

Dr Ben Cocks Research Director Animal Genetics and Genomics

Dr Ben Cocks – BSc (Hons), PhD
Email: ben [dot] cocks [at] dpi [dot] vic [dot] gov [dot] au

Dr Cocks has extensive expertise in the development and effective
application of genomics and new technologies relevant to biological

Prior to his appointment at DPI, he established a group at Incyte
Corporation in California that combined expertise in genomics, high-
throughput sequencing, microarrays, applied bioinformatics, genetics,
and proteomics to unravel disease mechanisms and to identify and
validate new drug targets.

Prior to working at Incyte, Dr Cocks participated in the discovery of
new pathways in lymphocyte biology central to parasitic responses and
inflammatory diseases in positions at DNAX Research Institute, Palo
Alto, California, USA and in the Department of Medicine at the
University of Melbourne. These included the discovery of IL-13
(McKenzie et al. 1993 Proc. Natl. Acad. Sci. USA 90, 3735-3739) and
its activity as a switch factor for IgE production in human B cells
(Cocks et al. 1993 Int. Immunol. 5, 657-663; Punnonen et al. 1993
Proc. Natl. Acad. Sci. 90, 3730-3734), as well as the identification
of SLAM as a key signaling receptor important for T and B cell
interaction and activation (Cocks et. al.1995 Nature 376, 260-263).

He also contributed to the knowledge of transcription regulation and
cell-cycling (Cocks et al. 1992 J.Biol.Chem. 267, 12307-12310) in
models of immune cell function (Hamilton et al. 1991 Blood 77,
616-627). Dr Cocks was trained in biochemistry at the University of
Melbourne where he made contributions to the discovery of new
metabolic pathways and the analysis of genomic structure in infectious

At DPI, Dr Cocks directs research in the effective application of
genetics genomics, and new technologies relevant to animal production,
animal health, and the identification of bioactive proteins.

Selected Publications

Cocks BG and Theriault TP (2004) Developments in effective application
of small inhibitory RNA (siRNA) technology in mammalian cells. Drug
Discovery: Targets 4: 165-171

Zingoni A, Sornasse T, Cocks BG, Tanaka Y, Santoni A and Lanier LL
(2004) Cross-talk between human NK cells and CD4+ T cells via OX40 –
OX40 ligand interactions. J. Immunol 173: 3716-24

Bandman O, Coleman RT, Loring JF, Seilhamer JJ and Cocks BG (2002)
Complexity of inflammatory responses in endothelial cells and vascular
smooth muscle cells determined by microarray analysis. Ann N Y Acad
Sci 975: p. 77-90.

Cocks BG, Chang CC, Carballido JM, Yssel H, de Vries JE, and Aversa G
(1995) A novel receptor involved in T-cell activation. Nature 376:

Cocks BG, de Waal Malefyt R, Galizzi JP, de Vries JE, and Aversa G
(1993) IL-13 induces proliferation and differentiation of human B
cells activated by the CD40 ligand. Int Immunol 5(6): p. 657-63.

Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, de
Waal Malefyt R, and de Vries JE (1993) Interleukin 13 induces
interleukin 4-independent IgG4 and IgE synthesis and CD23 expression
by human B cells. Proc Natl Acad Sci U S A 90(8): p. 3730-4.

Cocks BG, Vairo G, Bodrug SE, and Hamilton JA (1992) Suppression of
growth factor-induced CYL1 cyclin gene expression by antiproliferative
agents. J Biol Chem 267(17): p. 12307-10.

Cocks BG, Pyle LE, and Finch LR (1989) A physical map of the genome of
Ureaplasma urealyticum 960T with ribosomal RNA loci. Nucleic Acids Res
17(16): p. 6713-9.

Cocks BG, Brake FA, Mitchell A and Finch LR (985) Enzymes of
intermediary carbohydrate metabolism in Ureaplasma urealyticum and
Mycoplasma mycoides subsp. mycoides. J Gen Microbiol 131 ( Pt 9): p.