Genomics- empowering probiotic discovery and development

08 December 2016

In recent years, antibiotic resistant bacteria or “superbugs” have become one of the most perplexing health issues worldwide. These “superbugs” not only threaten available treatment options but are also responsible for causing recurrent infections. If ignored, antibiotic resistant bacteria could catapult us back to the pre-antibiotic era where simple infections couldn’t be contained and caused immense harm.

We spoke with Dr Hanna Sidjabat from The University of Queensland Centre for Clinical Research (UQCCR) to discover how genomics is allowing her team to further their research into probiotic discovery and development in the war against pathogens.

Dr Sidjabat's vision is to establish a preventative strategy for application to eliminate the colonisation by superbugs and other pathogens in the upper airway using probiotics. Dr Sidjabat is a microbiologist who leads the microbiology work of Professor Anders Cervin in research into upper respiratory tract microbiome and Australian Indigenous children with otitis media.

Respiratory Tract Infections (RTIs) continues to affect the both urban and rural population of Australia. Chronic rhinosinusitis (CRS) is a chronic inflammation of upper airway and affects 10% of the population. Amongst Australian Indigenous children, middle ear infections or otitis media (OM) is a commonly encountered infection.

“Our research team has been screening probiotic strains from children and adult participants; including pathogens colonising the upper airway of Australian Indigenous Children” Hanna explains. The aim of the project is to prevent infections of respiratory tract and ears using commensal bacteria.

In a collaboration between UQCCR and Deadly Ears (Queensland Government Initiative), Dr Sidjabat’s team has commenced a research program exploring the normal bacterial flora in the upper airway in the Australian Indigenous population and how this maintains health. “The aim is to investigate the possibility of strengthening the mucosal defence against recurring otitis media by supplementing the airway with beneficial bacteria. The concept is called reversing dysbiotic microbiome by recolonization of the mucosal membrane with commensals with probiotic properties.

The strains with beneficial or probiotic properties out-compete bacteria causing infections. We have an expectation that this treatment option in the future can reduce disease burden as well as reducing the use of antibiotics”, advises Dr Sidjabat.

Genomics and probiotic discovery

There are three major steps in the groups’ microbiology pipeline for probiotic discovery and development. The first step using a conventional microbiology approach is the identification of microbiota through the isolation of bacterial pathogens and the commensal bacteria residing in the mucosal membrane of the nose, throat or oral cavity.

In the second stage of the project the group characterises both pathogens and the commensal bacteria using molecular microbiology. War on the Petri dish also takes place at this stage through in vitro testing of probiotic strains against respiratory and ear pathogens, resulting in phenotypic characterisation of the probiotic strains.

The third stage employees next generation sequencing techniques for whole genome sequencing of probiotic strains for the purpose of genotypic characterisation in particular focussing on the characterisation of bacteriocins, other operons related to antimicrobial activity, virulence genes and antibiotic resistance genes. Proteomic characterisation is also included at this stage in order to profile the probiotic strains to measure the level of bacteriocins and other proteins related to antimicrobial activity.

Working with AGRF for the Whole Genome Sequencing component of the project has allowed the group to advance their genotypic knowledge of the probiotic strains to support their findings and ensure they know all there is to know about the strains identified. In particular identifying the genes and operons responsible for the killing activity against the pathogens is imperative to support the groups’ research. AGRF has provided quality data, customer support and strong technical assistance which is paramount to augmenting probiotic discovery and development.

Thus far, the research team has determined a strong correlation between the in vitro phenotypic testing of the Lactobacillus probiotic strains against the pathogens with the data from whole genome sequencing.

In the meantime, the research team has established a link with a prominent probiotic manufacturer to explore a pathway to be able to use these probiotic strains for clinical trials. The links with industry will enable the group to develop the formula and appropriate packaging for appropriate administrations.

Further information

About Probiotic Discovery and Development
www.facebook.com/probioticDD/about/
About UQCCR
www.uqccr.uq.edu.au
About Deadly Ears
www.health.qld.gov.au/deadly_ears/
Find Hanna Sidjabat on twitter: @DrHannaSidjabat