Proteomic analysis of mycobacterial biofilms enables global overview of key mechanisms regulating antibiotic resistance.

A new collaborative study by researchers in Finland and Norway – including PCF head Tuula Nyman – provides novel insights into how mycobacteria can escape elimination by antibiotics. These findings could have important implications for treating mycobacteria-driven diseases such as Tuberculosis.

 

Tuberculosis (TB) is an infectious disease most commonly caused by the bacterium Mycobacterium tuberculosis (Mtb). This disease represents a major global health concern, with approximately 10 million new cases and 1.4 million deaths in 2019. Around one quarter of the human population is thought to carry Mtb as an asymptomatic infection, but 5-10% of infected people will develop TB, which primarily affects the lungs.

Antibiotic resistant mycobacteria

Treatment of TB involves the use of several antimicrobial drugs over a period of at least 6 months. Whilst this can be curative for many patients, the emergence of drug-resistant Mtb strains is a major health concern.

The publication follows collaborative work between researchers from Norway and Finland. Left: first author Kirsi Savijoki from the University of Helsinki, Finland. Middle: corresponding author Mataleena Parikka from Tampere University, Finland. Right: NAPI Project Manager and co-author Tuula Nyman from the University of Oslo/Oslo University Hospital.

Indeed, studies have shown that even those patients who have been effectively ‘cured’ using antibiotics (i.e. disease symptoms were alleviated) can still possess viable and infectious Mtb in their lungs and sputum.

A clear understanding of all mechanisms that allow mycobacteria such as Mtb to escape cell death by antibiotics is lacking. However, it is known that one of the key factors involves a strong physical barrier provided by the bacterium’s so-called ‘biofilm’. This is a thick, complex matrix that sits outside the bacterial cell and is made up of a range of molecules including proteins, polysaccharides and DNA/RNA. The biofilm provides mycobacteria with protection against both host defence systems (e.g. human immune cells) and therapeutic antibiotics, as these factors struggle to cut through the biofilm and access the bacterial cell.

Proteomic analysis of biofilms

In a recent publication in the journal mSystems, researchers from Finland and Norway attempted to gain more insight into how the various stages of biofilm production in mycobacteria help to avoid elimination by antibiotics. To achieve this, the researchers used mass spectrometry-based proteomics to perform a systems-wide analysis of the biofilm components of Mycobacterium marinum (Mmr). This is a commonly used model for Mtb infections, and allows researchers to investigate TB-like latent and chronic stages of infection without the health and safety risks associated with working with Mtb itself.

Dr Tuula Nyman is the Project Manager of NAPI, and Head of the NAPI Proteomics Core Facility at University of Oslo/Oslo University Hospital where the mycobacterial biofilms were analysed in this study. Explaining the approach in more detail, Dr Nyman said:

“Our colleagues in Finland cultured an Mmr strain named ATCC 927 to create in vitro biofilms at different times over a 3-month culture period. As a control, they also isolated cell surface proteins from mycobacteria under non-infectious planktonic-type growth, which enabled the identification of proteins that are exclusive to biofilms from infectious bacteria. They then imaged these biofilms using microscopy to visualise structural properties, but also sent samples to our facility in Oslo so that we could investigate the protein components by mass spectrometry. Together, these analyses revealed some interesting patterns of protein composition across different stages of infection.”

Note: This content is copied from NAPI website

 
Page visits: 151