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Why bacterial carriage matters for antimicrobial resistance

Staphylococcus aureus bacteria. Image credit: Dave Goulding / Wellcome Sanger Institute

Why bacterial carriage matters for antimicrobial resistance

By Katrina Costa, Science Writer, Wellcome Sanger Institute

The CARRIAGE study, co-led by the Wellcome Sanger Institute and the University of Cambridge, reveals critical insights into the role of Staphylococcus aureus in antimicrobial resistance (AMR). MRSA is a key player in AMR, and this escalating global health crisis needs urgent solutions. We recently caught up with Dr Ewan Harrison, Group Leader at the Sanger Institute, to discuss how the CARRIAGE study impacts our understanding of how to tackle AMR.

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Unravelling antibiotic resistance

Imagine a world where a simple bacterial infection could threaten humanity, much like the fate of the Martians in The War of the Worlds by H.G. Wells. The global rise of antimicrobial resistance (AMR) is one of the biggest threats we face – and it is getting harder to ignore. In February, the World Health Organization published its first global research agenda to tackle AMR,1 following a stark warning in The Lancet that AMR infections could cause over 39 million deaths between now and 2050.2 With climate change potentially accelerating the crisis,3 we urgently need research into the biology of infectious diseases and how drug resistance spreads, alongside new options for diagnosis and treatment.

In 2019, methicillin-resistant Staphylococcus aureus (MRSA), a well-known deadly superbug that is resistant to methicillin-based antibiotics, caused over 100,000 deaths globally.2 In total that year, S. aureus was responsible for over a million deaths worldwide.4 Many people carry S. aureus without any symptoms, with the bacteria living on them harmlessly, which is known as bacterial carriage. Around 30 per cent of people carry S. aureus without symptoms globally,5 but it can sometimes cause infections ranging from minor skin conditions, such as boils, to more serious bone and joint infections and heart-valve infections, culminating in life-threatening illnesses like sepsis, which is triggered by an extreme immune reaction to the infection. In March 2025, the UK Health Security Agency named S. aureus in the top 24 infectious diseases that may pose the greatest future threat to public health.6

Understanding the carriage of S. aureus – especially why some people go on to develop infections whilst others do not – is crucial for preventing S. aureus and for tackling the spread of MRSA. As part of this effort, the CARRIAGE study was set up to investigate the genetic, biological and environmental factors behind S. aureus carriage, which uncovers new insights into fighting antibiotic-resistant infections. This project is the largest of its kind, with over 20,000 participants, and is a multidisciplinary study involving researchers at the Sanger Institute, University of Cambridge, Imperial College London and University of Birmingham and is led by Dr Ewan Harrison. This work aligns with Wellcome’s strategic priority to address drug-resistant infections7 by leveraging the Sanger Institute’s world-leading genomic technologies.

Just like our gut microbiome, there is a busy community of microorganisms, including bacteria and viruses, living in our noses, throats, and sinuses. The nasal microbiome keeps us healthy by supporting our immune system and protecting us from pathogens. There are fewer species in our noses than in our guts – commonly, we find approximately 30 versus over 1,000.8,9 Despite being relatively simple, the nasal microbiome remains understudied, likely holding clues about our health and how we respond to infection.

“Understanding the nasal microbiome, and especially S. aureus carriage, is crucial for tackling S. aureus infections. S. aureus carriers have a higher risk of developing an infection. That is why hospitals swab patients – they are specifically looking for people who carry MRSA so they can be given antibiotic creams and soap to prevent the further spread of MRSA.”

Ewan Harrison,
Group Leader, Respiratory Virus and Microbiome Initiative, Wellcome Sanger Institute

Given that carriers are more likely to develop infections,10 scientists must address an essential question: What factors influence who carries S. aureus? The CARRIAGE study takes us a step closer to the answer.

Exploring the genetics of Staphylococcus aureus carriage

The CARRIAGE study recruited volunteers from across England who had previously taken part in trials of blood donation led by Professor John Danesh and colleagues at the University of Cambridge. Participants took at-home nose swabs over a three-week period, which they returned by post. Initially, the researchers tested the stability of samples in the post through a test run with 200 people.

After the successful pilot, the study expanded to 2,000 people sending in swabs and being prepared for sequencing at the Sanger Institute. The researchers identified which bacteria were present in each sample using 16S rRNA sequencing. Bacteria contain the 16S rRNA gene, which codes for part of the ribosome (the machines in cells that make proteins) and can be used like a barcode to identify bacterial species. It is an efficient and cost-effective way of sequencing thousands of bacteria, which the team used to identify strains of S. aureus and other bacteria from the swabs.

In 2017, the study scaled up to 20,000 people and collected 60,000 nasal samples. The team has recently switched from 16S rRNA sequencing to shotgun metagenomic sequencing – a powerful approach detailing all microbial DNA in a sample. This high-resolution technique can detect antibiotic resistance genes and show how widespread resistance is in S. aureus strains found in healthy people, as well as identify resistance genes in other nasal bacteria. By combining genetic data with lifestyle and behavioural information, the research shows what the nasal microbiome looks like when people carry S. aureus compared to when they do not. The data will be publicly available in the European Nucleotide Archive, removing any personally identifiable information.

“Understanding who carries Staphylococcus aureus in their noses helps us predict and potentially reduce the spread of antibiotic-resistant strains, especially MRSA, providing vital insights for future infection control.”

Katie Bellis
Staff Scientist, Respiratory Virus and Microbiome Initiative, Wellcome Sanger Institute

The results offer a snapshot of S. aureus carriage at scale, which will eventually help guide the management of resistant S. aureus strains and inform MRSA infection control.

What the CARRIAGE study scientists discovered about S. aureus

Historically, scientists classified S. aureus carriers into three categories:

  1. Persistent carriers: Consistently test positive for S. aureus and have a higher infection risk for S. aureus.
  2. Intermittent carriers: Occasionally test positive, and their infection risk has been less clear.
  3. Non-carriers: Rarely or never test positive for S. aureus and are often assumed to have the lowest risk of infection.

However, the CARRIAGE study redefines the colonisation relationship of S. aureus with humans. Persistent- and non-carriers had a distinct and predictable microbiome, whereas intermittent carriers had a microbiome that resembled either persistent- or non-carriers.

“We found there are really just two groups – people colonised by S. aureus in abundance and people who are not. The group labelled 'intermittent carriers' does not exist as a distinct biological group. Given the complex interplay between S. aureus and humans, this work enables us to better identify individuals at heightened risk of infection and transmission to vulnerable patients.”

Dinesh Aggarwal,
Visiting Researcher at the Wellcome Sanger Institute NIHR Clinical Lecturer in Infectious Diseases, Imperial College London

The team found there are seven common types of microbiome in human noses, and when S. aureus is present, it dominates – often making up over 50 per cent of the bacterial community. This means we can group the nasal microbiome into two patterns:

  1. S. aureus dominates, and overall microbial diversity is low.
  2. S. aureus is rare, and there is a greater variety of other bacteria.

Another interesting finding is that people less likely to carry S. aureus tended to have more of certain other bacteria in their noses, such as Dolosigranulum pigrum, Staphylococcus epidermidis and Moraxella catarrhalis. These neighbouring bacteria may crowd out or compete with S. aureus, but that requires further study.

Why bacterial carriage matters for controlling MRSA

MRSA spreads easily, especially in hospitals, making infection prevention and control essential. However, understanding carriage at scale in the wider community allows us to better define the biological relationship between S. aureus, which includes MRSA, and its human host. The CARRIAGE study addresses this research gap by studying people in the general population without symptoms, providing insights into how infections and resistance may develop outside of hospitals.

The large size of the CARRIAGE study, with over 20,000 participants, means it provides statistically robust results that can assist the researchers in drawing more accurate conclusions. The participants also provided detailed personal data, ranging from household size and pet ownership to recent antibiotic use. This rich information will enable the scientists to identify factors influencing S. aureus carriage and infection risk. Analysing this extensive dataset has relied on the large-scale sequencing technology available at the Sanger Institute.

Ten ways the Sanger Institute is tackling the global fight against AMR

Sanger Institute researchers are using advanced genomic technologies to analyse the AMR landscape of several different microorganisms. As the effects of AMR disproportionately affect under-resourced countries, the Sanger works with collaborators in those regions.

Why treating MRSA involves understanding bacterial colonisation

Amongst the most effective antibiotic treatment for S. aureus infections are the penicillin family, to which MRSA strains are resistant. Doctors can treat MRSA with alternative antibiotics, but the bacteria often carry resistance genes to these as well; there are often limited oral antibiotic options, and the antibiotics are less effective. For certain hospital procedures, such as joint replacements or plastic surgery, the guidance recommends that patients be routinely tested for MRSA carriage. If a patient tests positive and the surgery is urgent, doctors use alternative antibiotics to prevent infections during surgery.

Colonisation is the most common lifestyle of bacteria like S. aureus, in which they live and grow on the body without causing harm. An infection occurs when these bacteria invade tissues and cause damage. Hospital staff use decolonisation tools, such as an antiseptic wash and antibiotic creams, to remove potentially harmful bacteria from the body and reduce the risk of infection. While generally successful in the short term, these techniques can disrupt the microbiome, and recolonisation often occurs within weeks. Moreover, some bacteria are becoming resistant to decolonisation methods, complicating infection control.

It turns out that understanding colonisation is vital because a large proportion of severe widespread S. aureus infections – which result in blood poisoning, or bacteraemia – occur in people previously colonised by the bacteria without symptoms.10 Scientists do not fully understand why only some people become infected. By exploring the links between colonisation, carriage and infection, scientists are more likely to develop new detection tools and treatment options for MRSA.

Despite the risk of antibiotic resistance, removing S. aureus from the body may not always be beneficial. With so many people harmlessly carrying S. aureus, might there be hidden advantages to its presence? Research shows that whilst colonised people are more likely to suffer an S. aureus infection, they are also less likely to die from severe S. aureus infections than non-carriers. This suggests that S. aureus colonisation may offer protective benefits, which may impact how we manage bacterial carriage and infection risk in the future.

Culturing and sampling bacteria for the CARRIAGE study. From left to right: Patient samples, Katie Bellis working in the lab, and culturing the bacteria on a petri dish. Images credit: Carmen Denman Hume, Wellcome Sanger Institute.

Understanding bacterial carriage to help tackle MRSA

The CARRIAGE study provides researchers worldwide with a rich dataset, offering new opportunities for future scientific research across different countries and even cross-species interactions. Increased understanding of the diversity of S. aureus strains and their biology will help researchers discover new diagnostic and preventative tools for MRSA infections.

CARRIAGE researchers plan to collate the genetic, microbiome and lifestyle data into a shared model, which will show how each factor contributes to whether someone carries S. aureus and their risk of infection. In the future, they also plan to incorporate immunity data, improving scientists’ ability to predict infection risk factors and control MRSA across populations.

Ewan's team plans to apply these results to studying the nasal microbiomes of healthcare workers. Since healthcare workers are frequently exposed to antibiotics, they are a key group to study for understanding antimicrobial resistance. The research will investigate whether exposure to antibiotics increases the risk of AMR and whether certain conditions predispose people to carry antibiotic-resistant strains.

Building a genomics career exploring the nasal microbiome

Staff scientist Katie Bellis shares her passion for infectious disease research and personal insights into life at the Wellcome Sanger Institute.

Vaccine research offers hope for MRSA control

Finding new antibiotics is challenging, as detailed in Wellcome’s article: Why is it so hard to develop new antibiotics? That is why scientists are turning to vaccines to control bacterial infections and AMR. Evidence shows that vaccines reduce the need for antibiotics, making them a vital tool for reducing AMR.11 Moreover, unlike antibiotics, current evidence suggests that it is rare for bacteria to develop vaccine resistance.

Despite previous research efforts, scientists have yet to create a successful vaccine for S. aureus.12 The main challenge is our incomplete knowledge of S. aureus biology, especially surrounding how the bacterium evades the immune system. There are also unanswered questions about the potential benefits of S. aureus colonisation. Research addressing these areas, such as the CARRIAGE study, could significantly advance our progress towards developing effective vaccines.

The CARRIAGE study has taken 11 years, and with the growing threat of AMR, long-term research projects like this are paramount. Understanding S. aureus carriage is essential for effectively tackling MRSA, a leading contributor to the AMR crisis. Further research is urgently needed to support public health strategies against resistant infections. The CARRIAGE dataset gives researchers worldwide something they have been missing – large-scale information on S. aureus carriage in the wider community, helping us move closer to managing AMR effectively.

Find out more

References

  1. The World Health Organization. February 2025. Global research agenda for antimicrobial resistance in human health[Last accessed: March 2025].
  2. Naghavi, M et al. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. The Lancet 2025; 404: 1199–1226.
  3. 3. May 2024. Will climate change lead to more antimicrobial resistance? [Last accessed: March 2025].
  4. GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet 2022; 400: 2221–2248.
  5. 5. Centers for Disease Control and Prevention (CDC). April 2024. Staphylococcus aureus Basics. [Last accessed: March 2025].
  6. 6. BBC News. March 2025. Priority pathogens: UK draws up new disease-threat watch list. [Last accessed: March 2025].
  7. Wellcome. October 2020. Wellcome’s bold ambitions to improve health through our new strategy. [Last accessed: March 2025].
  8. Escapa IF et al. New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract. mSystems 2018; 3: e00187–18.
  9. Yang, J. et al. Species-Level Analysis of Human Gut Microbiota With Metataxonomics. Front. Microbiol. 2020; 11: 548276.
  10. Wertheim, HFL. et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. The Lancet. 2004; 364: 703 – 705.
  11. Wellcome. October 2024. Vaccines have a crucial role in tackling antimicrobial resistance. [Last accessed: March 2025].
  12. World Economic Forum. February 2016. Can we find a vaccine for Staph aureus? [Last accessed: April 2025].

2025-12-01T16:07:58+00:002 December 2025|

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