Join the Klebsiella Action Project (KAP): A Call for Klebsiella pneumoniae Global Collaborative Research Program

Recently, the World Health Organization (WHO) has sounded the alarm on the escalating global threat posed by hypervirulent Klebsiella pneumoniae (hvKp) sequence type (ST) 23, a pathogen now recognized as a serious public health threat due to its rapid spread and high mortality rates. In direct response, M20 Genomics is launching the Klebsiella Action Project (KAP), dedicated to accelerating research and innovation to combat this deadly bacterium.

The Urgent Threat of hvKp ST23

Klebsiella pneumoniae is a typically harmless gram-negative bacterium residing human mucosal surfaces of the oropharynx and gastrointestinal (GI) tract. However, the emergence of the hypervirulent hvKp ST23 strain has transformed this microbe into a formidable pathogen capable of causing severe, life-threatening infections in even healthy individuals, including pneumonia, bloodstream infections, and meningitis.

On July 31, 2024, the WHO report highlighted the global spread of hvKp ST23 carrying resistant genes to the carbapenem antibiotics across six WHO Regions. Countries including United States, United Kingdom, China, and France all have reported the existence of hvKp ST23. The strain's resistance to carbapenems, a last-line antibiotic, coupled with its rapid dissemination, particularly within healthcare settings, underscores its potential to trigger widespread outbreaks.

The Rising Clinical Challenge Caused by hvKp

The clinical implications of hvKp ST23’s global dissemination are dire. The WHO report emphasizes that infections caused by this strain are associated with significantly higher mortality rates due to its resistance to multiple antibiotics, including carbapenems. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have significantly higher mortality rates (30–60%) compared to infections with carbapenem-susceptible Klebsiella pneumoniae. The strain’s ability to evade treatment has made it a formidable challenge for healthcare providers, leading to extended hospitalizations, escalating medical costs, and a heightened risk of patient fatalities.

The urgent need for novel research, advanced diagnostics, and groundbreaking therapeutic interventions to combat this deadly bacterium is underscored by the strain's rapid global proliferation.

M20 Genomics at the Forefront of hvKp ST23 Research

M20 Genomics is a pioneer in single-cell sequencing technology for both eukaryotic and prokaryotic research. Our VITA single-cell transcriptome products, launched globally in 2022, empower scientists to conduct in-depth functional studies of microorganisms at the single-cell level. The VITA products enable researchers to:

• Unmask Drug Resistance: By examining gene expression at individual cell level, researchers can identify specific drug resistance genes and understand how they function within the bacterium.
• Characterize Bacterial Functional Heterogeneity: Understanding the diversity within bacterial populations is critical for identifying the subpopulations that contribute to antibiotic resistance and treatment failure.
• Explore Microbial Interactions: Facilitates the exploration of the complex interplay between Klebsiella pneumoniae and other microorganisms and provides the insights into how these relationships influence resistance and virulence.

VITA Single-Cell Transcriptome Products for Prokaryotic Samples

Notably, M20 Genomics has conducted single-cell transcriptome sequencing with the VITA products for over 5,000 microbial samples globally, with Klebsiella pneumoniae comprising 10% of these. VITA products yield a relatively high median gene count per valid cell – 182 in a representative sample (Table 1 and Figure 1) – which is competitive among similar technologies.

Furthermore, the single-cell level of gene expression profiles enables the precise detection of functional and phenotypic heterogeneity within bacterial populations, allowing for the identification of functionally distinct subpopulations (Figure 2). We believe this revolutionary technology will offer unparalleled tools for studying the resistance mechanisms and pathogenicity of hvKp ST23, aiding scientists unravel the complexities of this dangerous bacterium.

Table 1 Primary sequencing results of a Klebsiella pneumoniae pure culture sample

Figure1: Left: Violin plot illustrating the distribution of the gene count per valid bacterial cell.

Right: Violin plot illustrating the distribution of the UMI count per valid bacterial cell.

Figure 2: UMAP showing the clustering of Klebsiella pneumoniae cells in a pure culture, based on gene expression profiles.

Time to Act: Join KAP to Fight Against hvKp ST23

The WHO’s warning makes it clear: the time to act against hvKp ST23 is now. To further advance the understanding of hvKp ST23 and develop effective countermeasures, M20 Genomics is launching the Klebsiella Action Project (KAP). This initiative aims to empower the researchers worldwide in their pursuit of understanding and combating this deadly pathogen by leveraging the cutting-edge VITA single-cell transcriptome products. The average support per project is estimated at approximately $60,000 in value, subject to variations based on individual project requirements.

Program Details:

• Sample Type: antimicrobial resistant hypervirulent Klebsiella pneumoniae bacteria, ST23 preferable

• Submission Deadline: October 31, 2024
• Please submit your research proposal via academic@M20genomics.com.

M20 Genomics invites researchers worldwide to join KAP. Together, we can deepen our understanding of this deadly pathogen and develop new strategies to safeguard public health. Submit your project proposal by the deadline to participate in this critical initiative.

Let’s work together to combat hvKp ST23 and build a healthier future.

*Selected participants will be notified by email within two weeks of receipt.

Reference：

1. World Health Organization. (‎2024)‎. Antimicrobial Resistance, Hypervirulent Klebsiella pneumoniae - Global situation‎. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON527
2. " Antimicrobial Resistance Threats in the United States, 2021-2022." U.S. Department of Health and Human Services, CDC, 2024. Available at: https://www.cdc.gov/antimicrobial-resistance/data-research/threats/update-2022.html
3. European Centre for Disease Prevention and Control (ECDC). " Increase of hypervirulent carbapenem-resistant Klebsiella pneumoniae in the EU/EEA." ECDC, 2024. Available at: https://www.ecdc.europa.eu/en/news-events/increase-hypervirulent-carbapenem-resistant-klebsiella-pneumoniae-eueea
4. Ding L, Shen S, Chen J, Tian Z, Shi Q, Han R, Guo Y, Hu F. Klebsiella pneumoniae carbapenemase variants: the new threat to global public health. Clin Microbiol Rev. 2023 Dec 20;36(4): e0000823. doi: 10.1128/cmr.00008-23.
5. Lou, X. Du, P. Zhang, Q. Shi, X. Han, P. Lan, et al. Risk factors for infection and mortality caused by carbapenem-resistant Klebsiella pneumoniae: A large multicentre case–control and cohort study. J. Infect. (2022)
6. Liu Y, Jian Z, Wang Z, Yang A, Liu P, Tang B, Wang J, Yan Q, Liu W. Clinical Characteristics and Molecular Epidemiology of ST23 Klebsiella pneumoniae in China. Infect Drug Resist. 2023;16:7597-7611 https://doi.org/10.2147/IDR.S428067