Oleg Zhivetin
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Published Jul 22, 2007
A ‘superbug’ resistant to antibiotics – a terrifying prospect preoccupying
both the press and the medical profession. The most notorious superbug is
MRSA (methicillin resistant Staphylococcus aureus), which can cause
anything from skin infections to septicaemia or pneumonia, and can be fatal
in patients with suppressed immune systems.
MRSA has been around in hospitals for years, passed between patients,
between wards, between hospitals and nursing homes. But only one
antibiotic can control it. That, too, will become useless one day, meaning
that even small cuts infected with MRSA could become untreatable.
Phage Therapy
Developing new antibiotics is complex and time-consuming. Nick Mann’s
team at the Department of Biological Sciences is studying one promising
alternative therapy based on a group of viruses called bacteriophages
(‘phages’). Phages infect and kill bacteria. ‘One particular phage latches on
to one strain of a bacterium, leaving all other strains untouched,’ Mann
explains. ‘Inside the bacterium, the phage makes copies of itself. When it’s
made enough, the bacterium bursts open and is destroyed, releasing the
virus copies to infect new cells.’
This is how lytic phages behave. A second type – temperate phages – will
either do the same, or form a ‘stable relationship’ with the cell. Usually
during this time, they will not reproduce, but their genetic material will
become integrated into the cell’s own.
Mutants
Lytic phages that kill their host bacteria are the most obvious therapy
choice. But those that infect MRSA strains have proved difficult to find.
However, Mann’s team did observe some temperate phages living within
different strains of MRSA. Although temperate phages are not ideal for
therapy (they don’t always kill bacteria), his team realised that some phages
mutate naturally so that one key part of their genetic make-up is different.
The mutations mean they can’t live in a stable relationship with their host:
they will kill
the bacteria, and so could be used for therapy.
Isolating the mutants can be time-consuming and laborious. But Mann’s
team exploited a chemical technology to speed up mutation. Using a single
strain of phage, they produced strong evidence to show that mice were
protected against a single strain of MRSA. The results were so promising, in
fact, that three years ago, with the University’s support, Mann and his
colleague David Hodgson set up a company, Novolytics, to develop phage-
based therapy.
Cocktail
Mann’s team has now sequenced the genome of a phage to ensure that it is
not carrying any nasty ‘virulence’ genes. The results are reassuring.
Novolytics’ main thrust is to develop a cocktail of mutant phages that could
kill virtually all MRSA strains, while leaving other beneficial bacteria
unharmed. One idea is to develop a nasal spray, which patients and medical
staff could use to reduce transmission of MRSA. Another is to develop a
device to identify people carrying the bug in their nasal passages so they
know when to take the spray. Other targets are to develop creams or
injectable suspensions to treat wounds, and to create disinfectant products
for medical devices.
Mann’s research into marine phages is also producing some fascinating
insights into how viruses are involved in some of nature’s key processes.
Last year, he reported how phages were controlling photosynthesis in
phytoplankton in the world’s oceans. ‘As these phytoplankton produce a
significant proportion of the oxygen we breathe, it is fair to say that a
significant proportion of this oxygen may result from virus infection. We are
only just beginning to recognise the importance of phages in the world
around us.’
A ‘superbug’ resistant to antibiotics – a terrifying prospect preoccupying
both the press and the medical profession. The most notorious superbug is
MRSA (methicillin resistant Staphylococcus aureus), which can cause
anything from skin infections to septicaemia or pneumonia, and can be fatal
in patients with suppressed immune systems.
MRSA has been around in hospitals for years, passed between patients,
between wards, between hospitals and nursing homes. But only one
antibiotic can control it. That, too, will become useless one day, meaning
that even small cuts infected with MRSA could become untreatable.
Phage Therapy
Developing new antibiotics is complex and time-consuming. Nick Mann’s
team at the Department of Biological Sciences is studying one promising
alternative therapy based on a group of viruses called bacteriophages
(‘phages’). Phages infect and kill bacteria. ‘One particular phage latches on
to one strain of a bacterium, leaving all other strains untouched,’ Mann
explains. ‘Inside the bacterium, the phage makes copies of itself. When it’s
made enough, the bacterium bursts open and is destroyed, releasing the
virus copies to infect new cells.’
This is how lytic phages behave. A second type – temperate phages – will
either do the same, or form a ‘stable relationship’ with the cell. Usually
during this time, they will not reproduce, but their genetic material will
become integrated into the cell’s own.
Mutants
Lytic phages that kill their host bacteria are the most obvious therapy
choice. But those that infect MRSA strains have proved difficult to find.
However, Mann’s team did observe some temperate phages living within
different strains of MRSA. Although temperate phages are not ideal for
therapy (they don’t always kill bacteria), his team realised that some phages
mutate naturally so that one key part of their genetic make-up is different.
The mutations mean they can’t live in a stable relationship with their host:
they will kill
the bacteria, and so could be used for therapy.
Isolating the mutants can be time-consuming and laborious. But Mann’s
team exploited a chemical technology to speed up mutation. Using a single
strain of phage, they produced strong evidence to show that mice were
protected against a single strain of MRSA. The results were so promising, in
fact, that three years ago, with the University’s support, Mann and his
colleague David Hodgson set up a company, Novolytics, to develop phage-
based therapy.
Cocktail
Mann’s team has now sequenced the genome of a phage to ensure that it is
not carrying any nasty ‘virulence’ genes. The results are reassuring.
Novolytics’ main thrust is to develop a cocktail of mutant phages that could
kill virtually all MRSA strains, while leaving other beneficial bacteria
unharmed. One idea is to develop a nasal spray, which patients and medical
staff could use to reduce transmission of MRSA. Another is to develop a
device to identify people carrying the bug in their nasal passages so they
know when to take the spray. Other targets are to develop creams or
injectable suspensions to treat wounds, and to create disinfectant products
for medical devices.
Mann’s research into marine phages is also producing some fascinating
insights into how viruses are involved in some of nature’s key processes.
Last year, he reported how phages were controlling photosynthesis in
phytoplankton in the world’s oceans. ‘As these phytoplankton produce a
significant proportion of the oxygen we breathe, it is fair to say that a
significant proportion of this oxygen may result from virus infection. We are
only just beginning to recognise the importance of phages in the world
around us.’
"Fighting the Superbug"
http://www2.warwick.ac.uk/about/warwickmagazine06/superbug/
http://www2.warwick.ac.uk/about/warwickmagazine06/superbug/
