What Does Whole Genome Sequencing Reveal About Anaerobic Bacteria?

As part of our Clinical Anaerobic Bacteriology Webinar Series, we recently hosted a session exploring what whole genome sequencing (WGS) reveals about anaerobic bacteria, led by Trefor Morris, Lead Biomedical Scientist at the UK Anaerobe Reference Unit (UKARU), Public Health Wales.

In this session, Trefor Morris provided a comprehensive overview of how whole genome sequencing is transforming our understanding of anaerobic bacteria, from clinical diagnostics and antimicrobial resistance to wider roles in human health and disease.

Key topics covered included:

• The diversity and clinical significance of anaerobic bacteria
• The evolution of sequencing technologies and the rise of WGS
• How WGS is improving diagnostic workflows and turnaround times
• The role of WGS in species identification, typing, and reclassification
• Detection and evolution of antimicrobial resistance in anaerobes
• Emerging insights into the role of anaerobes in health, disease, and beyond

Below, we expand on these themes in more detail for those who were unable to attend live, or who would like a consolidated technical overview of the session.

Setting The Context

The UK Anaerobe Reference Unit (UKARU), based within Public Health Wales, provides a national reference service for anaerobic bacteriology, including organism identification, antimicrobial susceptibility testing, surveillance, and clinical advice.

With over 80,000 clinical isolates held within its collection, UKARU plays a critical role in supporting laboratories across the UK, alongside delivering education and training through initiatives such as the Practical and Clinical Microbiology of Anaerobes (P&CMAn) course.

Trefor Morris brings over two decades of experience in clinical anaerobic microbiology, with a particular focus on maintaining strong foundational laboratory skills alongside the integration of emerging genomic technologies.

Anaerobic Bacteria: Diversity and Clinical Complexity

Anaerobic bacteria represent a highly diverse group of organisms, first described by Louis Pasteur in the 19th century as organisms capable of “life without oxygen”.

They are a major component of the human microbiota and are implicated in a wide range of infections, often arising from endogenous sources when normal physiological barriers are disrupted. These infections are frequently polymicrobial, involving complex interactions between anaerobic and aerobic organisms.

Clinically significant genera include:

• Clostridium spp. (including neurotoxic, histotoxic and enterotoxic groups)
• Bacteroides spp., particularly Bacteroides fragilis
• Fusobacterium spp., including Fusobacterium necrophorum and Fusobacterium nucleatum

The complexity of these infections, combined with the fastidious nature of many anaerobes, continues to present challenges for routine diagnostic laboratories.

The Evolution of Whole Genome Sequencing

Sequencing technologies have evolved significantly over the past several decades, from early work on DNA structure by Rosalind Franklin and the description of the double helix by James Watson and Francis Crick, through to the development of Sanger sequencing by Frederick Sanger.

Modern sequencing approaches now include:

• Short-read sequencing technologies, widely adopted in clinical laboratories
• Long-read sequencing, enabling more complete genome assembly
• True whole genome sequencing, providing high-resolution genomic data

This progression has enabled a shift from targeted genetic analysis to comprehensive genomic characterisation, with significant implications for clinical microbiology.

Impact on Clinical Diagnostics

A key theme of the webinar was the transformative impact of WGS on diagnostic workflows.

Traditional typing methods often involve complex, multi-step processes that can take several weeks to complete. In contrast, genomics-based pathways can deliver more detailed information in a significantly reduced timeframe, often within days.

Importantly, WGS:

• Enhances resolution and accuracy of organism identification
• Enables rapid comparison with global genomic databases
• Supports faster and more informed clinical and infection control decisions
• Has the potential to be applied directly from clinical samples, further reducing turnaround times

While culture remains a critical component of the diagnostic pathway, the integration of WGS is fundamentally reshaping how laboratories approach microbial characterisation.

Advancing Species Identification and Classification

Whole genome sequencing has significantly expanded our understanding of anaerobic taxonomy.

Key advances include:

• Identification of novel species, such as newly characterised anaerobes identified through genomic analysis
• Refinement and reclassification of existing species, improving taxonomic accuracy
• Greater understanding of genomic diversity within species

A well-known example is the reclassification of Clostridium difficile to Clostridioides difficile, reflecting its distinct genetic identity and evolutionary lineage.

WGS has also highlighted important distinctions within species such as Bacteroides fragilis, where genetically distinct divisions exhibit differing resistance mechanisms and metabolic profiles.

Typing and Surveillance: A Step Change

WGS has brought a step change in bacterial typing and surveillance.

At UKARU, traditional methods such as PCR ribotyping have been replaced by WGS for organisms including C. difficile, enabling:

• High-resolution strain differentiation
• Assignment of genomic clusters based on SNP analysis
• Improved detection of transmission events and outbreaks

Turnaround times have also improved significantly, with many sequencing workflows now delivering results within 7–10 days, and often faster.

This enhanced resolution supports more effective infection prevention and control, as well as more robust epidemiological surveillance.

Antimicrobial Resistance: Detection and Evolution

Another major area of impact is the detection and characterisation of antimicrobial resistance (AMR).

WGS enables:

• Identification of novel resistance genes
• Improved understanding of resistance mechanisms and evolution
• Detection of multi-drug resistant strains, particularly in Bacteroides species
• Monitoring of emerging resistance trends at population level

However, an important point emphasised in the session is that genotypic prediction of resistance does not yet fully replace phenotypic susceptibility testing. Correlating genomic data with clinical breakpoints remains an ongoing area of research.

The continued use of robust susceptibility testing methods alongside WGS remains essential to ensure accurate clinical interpretation.

Horizontal Gene Transfer and Genetic Mobility

Whole genome sequencing is also revealing the extent of horizontal gene transfer (HGT) among anaerobic bacteria.

This includes:

• Transfer of resistance determinants between species
• The role of mobile genetic elements, such as transposons and plasmids
• Evidence of gene exchange occurring within individual clinical samples

These findings have significant implications for the spread of antimicrobial resistance and highlight the dynamic nature of anaerobic microbial populations.

Beyond Infection: Anaerobes in Health and Disease

Beyond their role as pathogens, anaerobic bacteria play a critical role in human health and disease.

WGS has contributed to growing insights into:

Colonisation resistance and microbiome function

Anaerobes produce short-chain fatty acids, which are key to maintaining colonisation resistance and preventing pathogen overgrowth. Genomic analysis supports the selection of specific strains for potential probiotic applications.

Disease associations

WGS is helping to characterise associations between anaerobes and a range of conditions, including:

• Inflammatory bowel disease (Faecalibacterium prausnitzii)
• Colorectal cancer (Fusobacterium nucleatum)
• Obesity and metabolic disorders
• Bacterial vaginosis and treatment response
• Periodontal disease and systemic inflammation

These insights are driving a more nuanced understanding of the microbiome and its role in health.

Key Takeaways

Trefor Morris concluded with several important messages:

• Whole genome sequencing is transforming our understanding of anaerobic bacteria
• WGS is enhancing diagnostics, typing, and surveillance, while reducing turnaround times
• Antimicrobial resistance is evolving, with increasing evidence of multi-drug resistance
• Genotypic methods do not yet replace phenotypic susceptibility testing, which remains essential
• Anaerobes play a significant role in both disease and health, with ongoing discoveries being driven by genomic technologies

Watch the Webinar On-Demand

If you missed the live session, or would like to revisit the discussion in full including the exclusive Q&A section, you can watch the recorded What Does Whole Genome Sequencing Reveal About Anaerobic Bacteria? webinar by filling in the form below.

For updates on future sessions in our Clinical Anaerobic Bacteriology Webinar Series, or to learn more about our anaerobic workstations and solutions for microbiology laboratories, please visit www.dwscientific.com.