Infectious diseases are responsible for high global mortality rates and contribute substantially to morbidity rates. Since ancient times, infectious diseases have affected humankind. These include tuberculosis, smallpox, plague and malaria. Tuberculosis is estimated to have caused around 1 billion deaths1, while smallpox caused approximately 300–500 million fatal infections before its eradication in the 1980s2. Certain regions of the world face the re-emergence of infectious diseases that were previously under control (for example, measles and polio).

The landscape of infectious diseases continues to evolve, and with that evolution, threats grow. Indeed, a study from 2019 reported that 33 bacterial pathogens were responsible for an estimated 13.7 million infection-related deaths in that year3. Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa accounted for more than half of the total number of deaths. Although COVID-19 has seen a recent decline, diseases such as tuberculosis4, malaria5 and HIV/AIDS6, which are treatable or preventable, continue to pose major threats, causing around 1.25, 0.6 and 0.6 million deaths each year, respectively. Similarly, a 2024 analysis looking at the global incidence and mortality of severe fungal disease estimated that fungal pathogens cause around 6.5 million invasive infections and 3.8 million deaths per year7. Although vaccines, antimicrobials and other strategies are available to prevent or treat many of these pathogens, the impacts of infectious disease are undeniable, and finding ways to overcome them should be a collective priority. Indeed, the World Health Organization has published priority pathogen lists for pathogenic bacteria8 and fungi9. In general, approaches to manage infectious diseases include vaccinations, the use of antimicrobials, good hygiene practices, safe food handling and public health measures, such as surveillance and forecasting. In this Focus issue, we put a spotlight on emerging threats (for example, environmental fungal resistance) and improving existing tools in our defence against infectious disease (for example, vaccines).

One of the most established and efficient ways of tackling infectious disease is vaccination. In this issue, a Review by Lentacker and colleagues discusses bacterial mRNA vaccine design. The authors provide an overview of bacterial mRNA vaccines currently under pre-clinical and clinical development and consider ways to improve the translatability of these vaccines. This is especially important as bacterial vaccines are not yet as common as viral vaccines. Understanding how existing vaccines work is also important. For example, the yellow fever vaccine 17D is currently the most effective live-attenuated vaccine against yellow fever; however, the reasons that the strain is attenuated are largely unknown. In an Article, Ploss and colleagues provide insight into why specific mutations contribute to attenuation of 17D. These findings could have important implications for designing more effective live-attenuated vaccines in other viruses.

Good hygiene practices are fundamental for tackling infectious diseases. This includes water, sanitation and hygiene (WASH)10 practices but also safe and regulated food production. An Article by Alvarez-Ordóñez and colleagues characterized the metagenomes of 1,780 raw material, end-product and surface samples from 113 food-processing facilities. They found that the majority of all known bacterial antimicrobial resistance genes (more than 70%) circulate throughout food production chains daily, although for most resistance genes, the prevalence and abundance is relatively low. In a related News & Views article, Kate Baker notes that the results represent an opportunity to consider intervention measures for contaminated surfaces in food production. Baker also makes a point that more work is required to understand the drivers of antimicrobial resistance in food processing environments, and to determine the relevance of antimicrobial resistance genes on food products for human health.

Bacterial antimicrobial resistance is well documented, but rising antifungal drug resistance, coupled with the limited arsenal of antifungal drugs, is also a major problem. The increased use of fungicides in the environment, and the potential associated risk of acquisition of resistance and cross-resistance to antifungal drugs used in clinical settings, pose additional serious agricultural and human health threats11,12. In a Review, van Rhijn and Rhodes discuss the emergence and expansion of antifungal resistance in the environment, and outline alternative approaches to reduce antifungal resistance. These include the use of combinations of multiple fungicides with distinct modes of action (to reduce the likelihood of resistance development), the diversification of the crops used (to reduce selective pressure on fungal populations), the development of new antifungal and fungicide drug classes, and improved genomic surveillance.

Although the development of antimicrobials is critical for our ability to overcome infectious diseases, understanding the biology of these diseases and developing preventive measures are also key. In this issue, Tadesse recounts his personal experience of fighting malaria both as a patient during childhood and later as a scientist in Ethiopia. Tadesse stresses how studying drug resistance, diagnostic escape mutations in the Plasmodium parasites and mosquito-mediated transmission will be crucial to tackle malaria. Tadesse leads the Horn of Africa Malaria Molecular Surveillance (HAMMS) project supported by the Gates Foundation and involving several African countries. The HAMMS mission is to shed light on the spread of drug-resistant and diagnosis-evading Plasmodium strains, and to monitor their vector-mediated transmission. These efforts underscore the importance of infectious disease surveillance in fighting infectious diseases. In that regard, a Review by Tonkin-Hill and colleagues discusses the processes driving bacterial evolution and emergence of pathogenesis in hosts, within-host genetic diversity, and the implications for transmission analysis and infectious disease control.

This Focus issue covers only a handful of approaches that can and are being used to overcome infectious diseases. Others include bacteriophage (phage) therapy13, treatments such as microbiome-directed therapies or antibodies, and nanotechnology to deliver drugs, as well as preventive measures such as genomic surveillance, diagnostics, or engagement and education to increase uptake of interventions.

Besides major causes of infectious diseases such as tuberculosis, malaria and HIV/AIDS, we are witnessing additional emerging and re-emerging infectious diseases. From 2013–2016 there was the Ebola virus disease epidemic in West Africa; in 2015, the Zika virus disease epidemic; and in 2019, the ongoing COVID-19 pandemic14.Very recent pandemics include a measles outbreak in the USA and H5N1, Oropouche, mpox and Dengue fever outbreaks to name a few. Research has indicated that increased international travel, more people living in urban areas and climate change have all contributed to these outbreaks14. To help tackle current infectious diseases and prevent the emergence of new outbreaks, it will be important for research, industry, agriculture and governments to come together and collaborate on the development and implementation of the approaches described above. Only through investment in basic and translational research, and in public health measures, will we have a chance to overcome infectious diseases.