'Living medicine' created to treat drug-resistant infections
Experimental treatment dissolves antibiotic-resistant biofilms in mice


Date:
October 6, 2021
Source:
Center for Genomic Regulation
Summary:
Researchers have created 'living medicine' to treat
antibiotic-resistant bacteria growing on the surfaces of medical
implants. The researchers created the treatment by removing a
common bacteria's ability to cause disease and repurposing it to
attack harmful microbes instead. The findings are an important
first step for the development of new treatments for these type
of infections, which account for 80% of all infections acquired
in hospital settings.



FULL STORY ========================================================================== Researchers at the Centre for Genomic Regulation (CRG) and Pulmobiotics
S.L have created the first 'living medicine' to treat antibiotic-resistant bacteria growing on the surfaces of medical implants. The researchers
created the treatment by removing a common bacteria's ability to cause
disease and repurposing it to attack harmful microbes instead.


==========================================================================
The experimental treatment was tested on infected catheters in vitro,
ex vivo and in vivo, successfully treating infections across all three
testing methods.

According to the authors, injecting the therapy under the skin of mice
treated infections in 82% of the treated animals.

The findings are an important first step for the development of new
treatments for infections affecting medical implants such as catheters, pacemakers and prosthetic joints. These are highly resistant to
antibiotics and account for 80% of all infections acquired in hospital settings.

The study is published today in the journal Molecular Systems
Biology. This work has been supported by the "la Caixa" Foundation
through the CaixaResearch Health call, the European Research Council
(ERC), the MycoSynVac project under the EU's Horizon 2020 research and innovation programme, the Generalitat de Catalunya and the Instituto de
Salud Carlos III.

The new treatment specifically targets biofilms, colonies of bacterial
cells that stick together on a surface. The surfaces of medical implants
are ideal growing conditions for biofilms, where they form impenetrable structures that prevent antibiotics or the human immune system from
destroying the bacteria embedded within. Biofilm-associated bacteria
can be a thousand times more resistant to antibiotics than free-floating bacteria.

Staphylococcus aureusis one of the most common species of
biofilm-associated bacteria. S. aureus infections do not respond to conventional antibiotics, requiring patients to surgically remove any
infected medical implants.

Alternative therapies include the use of antibodies or enzymes, but
these are broad-spectrum treatments that are highly toxic for normal
tissues and cells, causing undesired side effects.

The authors of the study hypothesised that introducing living organisms
that directly produce enzymes in the local vicinity of biofilms is a
safer and cheaper way of treating infections. Bacteria are an ideal
vector, as they have small genomes that can be modified using simple
genetic manipulation.

The researchers chose to engineer Mycoplasma pneumoniae, a common
species of bacteria that lacks a cell wall, making it easier to release
the therapeutic molecules that fight infection while also assisting it
in evading detection from the human immune system. Other advantages of
using M. pneumoniae as a vector include its low risk of mutating new
abilities, and its inability to transfer any of its modified genes to
other microbes living nearby.

M. pneumoniae was first modified so that it would not cause
illness. Further tweaks made it produce two different enzymes that
dissolve biofilms and attacks the cell walls of the bacteria embedded
within. The researchers also modified the bacteria so that it secretes antimicrobial enzymes more efficiently.

The researchers first aim to use the modified bacteria to treat biofilms building around breathing tubes, asM. pneumoniaeis naturally adapted
to the lung. "Our technology, based on synthetic biology and live biotherapeutics, has been designed to meet all safety and efficacy
standards for application in the lung, with respiratory diseases being
one of the first targets. Our next challenge is to address high-scale production and manufacturing, and we expect to start clinical trials
in 2023," says Mari'a Lluch, co-corresponding author of the study and
Chief Science Officer of Pulmobiotics.

The modified bacteria may also have long-term applications for other
diseases.

"Bacteria are ideal vehicles for 'living medicine' because they can carry
any given therapeutic protein to treat the source of a disease. One
of the great benefits of the technology is that once they reach their destination, bacterial vectors offer continuous and localised production
of the therapeutic molecule.

Like any vehicle, our bacteria can be modified with different payloads
that target different diseases, with potentially more applications in
the future," says ICREA Research Professor Luis Serrano, Director of
the CRG and co-author of the study.

========================================================================== Story Source: Materials provided by Center_for_Genomic_Regulation. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Victoria Garrido, Carlos Pin~ero-Lambea, Irene Rodriguez-Arce,
Bernhard
Paetzold, Tony Ferrar, Marc Weber, Eva Garcia-Ramallo,
Carolina Gallo, Mari'a Collantes, Iva'n Pen~uelas, Luis
Serrano, Mari'a-Jesu's Grillo', Mari'a Lluch-Senar. Engineering a
genome-reduced bacterium to eliminate Staphylococcus aureus biofilms
in vivo. Molecular Systems Biology, 2021 DOI: 10.15252/msb.202010145 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211006095502.htm

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