A moment with Karrie Ko

Taking in the sights and sounds of Barcelona after a research conference // Credit: Courtesy of Karrie Ko  

A crusade against deadly microbes  
 By Dr Karrie Ko (Class of 2011); Consultant, Department of Microbiology, Singapore General Hospital; Director of Genomics, Pathology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre
 

It started just like any other day at the Singapore General Hospital’s Molecular Laboratory for Dr Karrie Ko.

Yet, amidst the routine testing for the formidable Candida auris, an unexpected anomaly in the samples set the stage for a groundbreaking discovery.

What began as a typical lab day quickly transformed into a significant leap forward in microbial genomics, reshaping our battle against one of the world’s most resilient hospital threats.

The drug-resistant fungus, which can kill about half of its victims within 90 days, affects mostly patients with severe underlying medical conditions. 

It spreads easily in hospitals, potentially closing wards with outbreaks caused by contact with infected patients and contaminated surfaces or equipment.

To mitigate such risks, SGH has an active surveillance programme to screen high-risk patients for Candida auris and isolate those who test positive—we get around 250 of such patient samples a month to analyse. 

But this time, there was something unusual.

One of the patients tested positive for the fungus, which is typically associated with travel.

But the patient had no travel history—he had not been overseas for two years at this point.

Intrigued, we investigated further to find out how he came to be harbouring the fungus.

We initially hypothesised that the fungus was a variant known as the East Asian Clade (Clade II), but cultures of our sample turned out to have growth characteristics and biochemical features that differed from all five known Candida auris clades, prompting us to investigate further.

The novel type of Candida auris grown in a petri dish

The novel type of Candida auris grown in a petri dish // Credit: Koh Tse Hsien

Our research team, which included experts from the Genome Institute of Singapore and the National University of Singapore’s Yong Loo Lin School of Medicine, performed whole-genome sequencing to read the fungus’ entire DNA makeup.

To better compare this against existing sequences, we decided to use a new algorithm that we had developed, to classify the fungus’ genome and identify anomalies.

The research team inspecting cultures of Candida auris

The research team: (from left) Dr Chayaporn Suphavilai, Ms Lim Kar Mun, Ms Tan Mei Gie, Associate Professor Niranjan Nagarajan and Dr Karrie Ko inspecting cultures of Candida auris // Credit: A*STAR’s Genome Institute of Singapore  

Comparing the genome of our patient’s Candida auris against an international genome sequence database, we generated more than six million genome pairs, revealing six distinct genetic clusters: the five known clades and a new one. 

We had indeed discovered a new variant, bringing the total number of Candida auris clades known globally to six.

By uncovering the new clade early, we can improve surveillance strategies to keep a close watch on its emergence and contain the spread. 

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If not for the mundane observation of the lack of recent travel history and a few usual traits, the new clade may have remained undetected even as it circulated, potentially developing into a silent outbreak.

Although our algorithm is still being tested, we showed that a machine learning approach can potentially be used to automatically classify microbial genomes. 

This means that we can take a culture isolate from a patient sample and read the entire sequence of DNA inside it. We can then feed the microbial genomes into our model, which can automatically classify genomes, and flag any unusual clusters or outliers for further investigation.

This will help to provide early alerts for any suspicious genome clusters or novel genomes, and safeguard patients from public health threats.

Apart from this work on Candida auris, I am interested in deploying microbial genomics and metagenomics to improve infectious disease surveillance and diagnostics. 

Metagenomic approaches save time by eliminating the need to grow the organism from the patient’s sample in a petri dish, which can be laborious and slow, before we can test what it is. 

Unlike the targeted nature of polymerase chain reaction (PCR) tests, metagenomic approaches can read all the nucleic acid present in the patient’s sample in an untargeted manner—giving it the potential to detect thousands of pathogens in a single test. 

Together with partners in the Genome Institute of Singapore and NUS Medicine, we are working to bring metagenomics into the clinical space.

Dr Karrie Ko generating and analysing microbial genomics data in one of the SGH labs

Dr Karrie Ko generating and analysing microbial genomics data in one of the SGH labs // Credit: Chayaporn Suphavilai  

Young and carefree buddies in medical school.

Young and carefree buddies in medical school. (From left) Dr Wong Ann Mei, Dr Karrie Ko, Dr Pamela Gopal, Dr Astrid Suantio, Dr Tan Tze Chin // Credit: Courtesy of Karrie Ko  

 
The power of the genome 

I have been fascinated with the possibilities of what we can achieve with genetics since I was a medical student. 

But in many ways, I started on this path on my sixth birthday when I received a much longed for toy microscope. 

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A young Karrie Ko with her beloved grandmother who raised her. Dr Ko couldn’t make it to grandma’s deathbed as there were still COVID travel restrictions // Credit: Courtesy of Karrie Ko  

I was the sort of kid who would scrape my skin to examine my own cells. Anything that could be squashed between two slides, I inspected under the microscope. I still have that toy microscope, which I teach my kids to do weird stuff with.

I am still driven by a sense of curiosity about the world, with my favourite question being “why?”  I cannot tahan (colloquial for put up with) why we do things in a certain way. Why are we not doing it better when we have the capability and technology to do so? Why are we not using a more efficient process? Why are we relying on a slower method when there is a faster one?

To address some of these questions, I’m hoping to set up a microbial genomics programme to better understand microbes of public health importance.

I hope to establish a surveillance programme where potentially deadly pathogens are sequenced either using whole-genome or metagenomic approaches and automatically flagged. In this way, we can then use microbial genomic data to generate actionable insights.

But I understand that this is likely to be a long and lonely road, despite all the support I have from my teammates and colleagues.

Venturing into academia is no easy path: it is one of intense challenge and, often, immense personal sacrifice.

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For those of us balancing clinical work, research work and family, the demands of work can weigh heavily.

My two young sons, six and nine, know all too well the phrase “Mama’s working, Mama’s very busy now.”

The boys resorted to writing on a post-it note, asking that I hug and kiss them before bed. Now affixed to my desk, this note serves as a daily reminder to step back from work, even if just for a moment, and be present for them.

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Family time with six-year-old Barry and nine-year-old Henry // Credit: Courtesy of Karrie Ko  

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The mundane moments are the most important. Grocery shopping and breakfast together are treats // Credit: Courtesy of Karrie Ko  

At the height of the pandemic, like many healthcare workers, I was rarely home. 

Balancing hospital work and graduate studies had me on overdrive, and my husband had to remind me to go home just so he could go out to buy groceries during the circuit breaker period.

It is my conviction that has kept me going through these challenges: I want to make a difference, to improve public health and surveillance—work that impacts us all.

My children remind me why I do this. 

For them and future generations, I will continue to ask questions and stay curious, advancing diagnostics and surveillance to help protect our shared future.


As told to Alice Chia, Senior media and content specialist.

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