Microbial Primers

The modern antibiotic era began in the early twentieth century, but humans have long used materials from the natural world to attempt to treat the symptoms of infection. In this primer, we will discuss the rationale for attempting to reconstruct historical infection remedies in order to assess their antimicrobial activity and how this approach could aid the discovery of molecular cocktails with potential for development into novel treatments for infection.

Artificial intelligence (AI) and machine learning (ML) are reshaping microbiology, enabling rapid antibiotic discovery, resistance prediction and clinical diagnostics. For microbiologists, the goal is not to build new algorithms but to recognize when ML is appropriate, how to prepare data and how to interpret outputs responsibly. This primer takes that practical stance – driving the ML car rather than rebuilding the engine. At a high level, ML learns from complex patterns, often noisy data. In antibiotic discovery, ML models help identify compounds in biological data and design new ones from scratch using generative AI. In microbiome studies, where measurements are compositional, sparse and often confounded, ML helps uncover community structure and link taxa or functions to phenotypes. In pathogen genomics, supervised models map sequence-derived features (e.g. k‑mers, SNPs and gene presence/absence) to outcomes such as species identity, antimicrobial susceptibility or MIC. Unsupervised learning supports exploration, including clustering, latent gradients and dimensionality reduction for visualization. Across these settings, success hinges less on exotic architectures than on sound problem framing, careful preprocessing and experimental validation.

Gram-positive bacteria commonly employ autoinducing peptide (AIP) signal molecules to co-ordinate gene expression at the population level. This primer provides a basic overview of agr-dependent quorum sensing systems and outlines how AIPs are produced and sensed, what they control and the importance of agr for both inter-bacterial and host–pathogen interactions.

Microbiome-animal host symbioses are ubiquitous in nature. Animal-associated microbiomes can play a crucial role in host physiology, health and resilience to environmental stressors. As climate change drives rising global temperatures and increases the frequency of thermal extremes, microbiomes are emerging as a new frontier in buffering vulnerable animals against temperature fluctuations. In this primer, we briefly introduce key concepts of microbiome-host symbiosis and microbial responses to temperature shifts. We then summarize the current evidence and understanding of how microbes can buffer the thermal stress faced by their hosts. We identify key challenges for future research. Finally, we emphasize the potential of harnessing microbiomes to improve conservation strategies in a rapidly changing climate, offering a concise overview of this evolving field.

The extracellular matrix of microbial biofilms has traditionally been viewed as a structural scaffold that retains the resident bacteria in the biofilm. Moreover, a role of the matrix in the tolerance of biofilms to antimicrobials and environmental stressors was recognized early in biofilm research. However, as research progressed it became apparent that the biofilm matrix can also be involved in processes such as bacterial migration, genetic exchange, ion capture and signalling. More recently, evidence has accumulated that the biofilm matrix can also have catalytic functions. Here we review foundational research on this fascinating catalytic role of the biofilm matrix.

The growth and success of many bacteria appear to rely on a stunning range of cooperative behaviours. But what is cooperation and how is it studied?

tGrowth of microorganisms and interpretation of growth data are core skills required by microbiologists. While science moves forward, it is of paramount importance that essential skills are not lost. The bacterial growth curve and the information that can gleaned from it is of great value to all of microbiology, whether this be a simple growth experiment, comparison of mutant strains or the establishment of conditions for a large-scale multi-omics experiment. Increasingly, the basics of plotting and interpreting growth curves and growth data are being overlooked. This primer article serves as a refresher for microbiologists on the fundamentals of microbial growth kinetics.

In this primer on biofilms and their role in infections, we trace the historical roots of microbial understanding from Van Leeuwenhoek’s observations to Bill Costerton’s groundbreaking work, which solidified biofilms' significance in infections. In vivo biofilm research, investigating patient samples and utilizing diverse host models, has yielded invaluable insights into these complex microbial communities. However, it comes with several challenges, particularly regarding replicating biofilm infections accurately in the laboratory. In vivo biofilm analyses involve various techniques, revealing biofilm architecture, composition, and behaviour, while gaps in knowledge persist regarding infection initiation and source, diversity, and the Infectious Microenvironment (IME). Ultimately, the study of biofilms in infections remains a dynamic and evolving field poised to transform our approach to combat biofilm-associated diseases.

Multidrug efflux pumps are molecular machines that sit in the bacterial cell membrane and pump molecules out from either the periplasm or cytoplasm to outside the cell. While involved in a variety of biological roles, they are primarily known for their contribution to antibiotic resistance by limiting the intracellular accumulation of antimicrobial compounds within bacteria. These transporters are often overexpressed in clinical isolates, leading to multidrug-resistant phenotypes. Efflux pumps are classified into several families based on their structure and understanding the characteristics of each family is important for the development of novel therapies to restore antibiotic potency.

Biofilms are complex communities of microbes that are bound by an extracellular macromolecular matrix produced by the residents. Biofilms are the predominant form of microbial life in the natural environment and although they are the leading cause of chronic infections, they are equally deeply connected to our ability to bioremediate waste and toxic materials. Here we highlight the emergent properties of biofilm communities and explore notable biofilms before concluding by providing examples of their major impact on our health and both natural and built environments.