- Volume 171, Issue 5, 2025

Novel strategies to counter multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus are urgently required. The antimicrobial properties of fatty acids (FAs) have long been recognized and offer significant promise as viable alternatives to, or potentiators of, conventional antibiotics. In this review, we examine the interplay between FAs and S. aureus, specifically detailing the underlying molecular mechanisms responsible for FA-mediated inhibition and the counteracting staphylococcal systems evolved to withstand FA onslaught. Finally, we present an update on the recent therapeutic FA applications to combat S. aureus infection, either as a monotherapy or in combination with antibiotics or host-derived antimicrobial peptides. Given the frequency of interaction between FAs and S. aureus during host colonization and infection, understanding FA mode of action and deciphering S. aureus FA resistance strategies are central in rationally designing future anti-staphylococcal FAs and FA-combination therapies.

Fatty acids have antimicrobial activity against a wide range of bacteria. We therefore aimed to incorporate omega-3 unsaturated alpha-linolenic acid (αLA) into the membrane of antibiotic-loaded liposomes to create a system with dual antibacterial activity against Helicobacter pylori. Liposomes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, sphingomyelin and the far-red fluorescent DiD label, with varying content of αLA (mol% to total lipid), were fabricated using the thin film evaporation method and hydrated with PBS or amoxicillin solution. The liposomes were characterized for αLA and amoxicillin content, particle size, membrane fluidity and permeability, prior to their addition to cultures of H. pylori strains and clinical isolates. αLA-modified liposomes enhanced the antibacterial action of amoxicillin against H. pylori, as determined using a viable count method. The liposomal formulation achieved a 3-log reduction in bacterial density, compared to a 1.5- to 2-log reduction by amoxicillin in solution. The application of imaging cytometry revealed a significantly increased association of αLA-modified liposomes with H. pylori cells, compared to non-αLA control liposomes. In conclusion, this study demonstrated, for the first time, that the incorporation of αLA increased the attraction of the liposomes to H. pylori and increased antibiotic potency. This suggests that αLA incorporation into liposomes may not only act as an antimicrobial, but also as a potential in vivo targeting strategy.

Dietary fibre is a crucial component of healthy diets via its action on the human gut microbiota, but fibre intake is well below current international dietary guidelines at the population level. Pectin is a fibre constituent in fruit and vegetables that has the promise to promote a healthy and diverse microbiota. It is a highly complex molecule, and its composition differs between plants. Here, we assessed the ability of a panel of 23 human gut bacteria to ferment pectins extracted from different plants based on their genome carriage of carbohydrate-active enzymes (CAZymes) and their growth in pure culture on several mono-, oligo- and polysaccharides, as well as pectins from different plant sources. Growth behaviour was overall in good agreement with CAZyme carriage, and the results were used to design synthetic co-culture communities with different combinations of pectin degraders, pectin cross-feeders and background strains not expected to play a major role in pectin degradation. For pectin degraders, Lachnospira eligens DSM 3376 outcompeted Phocaeicola vulgatus DSM 1447 and Segatella copri DSM 18205, which appeared to act more as a cross-feeder in the presence of L. eligens DSM 3376. Between the cross-feeders, Roseburia intestinalis M50/1 likely utilized breakdown products from the pectin backbone and side chains, whereas Faecalibacterium duncaniae A2-165 grew better in co-culture on homogalacturonan-rich pectins. Our work will help to explain individual-specific responses to pectin intake based on microbiota compositional variation and contribute to the design of personalized dietary strategies to optimize the microbiota.

We are surrounded, in both indoor and outdoor environments, by air containing particles of biological origin (bioaerosols). We constantly inhale them, and, depending upon their size, they deposit in different parts of our airways. Despite their ubiquitous nature and our constant exposure, bioaerosol diversity and composition of the environment are not well characterized, and we understand little about which bioaerosols we are exposed to and how this impacts our health, either positively or negatively. Indoor/Outdoor Bioaerosols Interface and Relationships Network (BioAirNet), a Clean Air Programme-funded network, has recognized the need for the bioaerosol community to reflect on the current challenges facing bioaerosol exposure assessment and the determination of the associated cellular/molecular responses driving specific health outcomes. A series of online workshops for the bioaerosol community were hosted by BioAirNet in September 2022, which aimed to bring together global expertise to discuss the current challenges impeding improved assessment of bioaerosol exposure and understanding of the downstream cellular and molecular mechanisms driving health outcomes by discussing these challenges; considering where we need to be, where we are now and how we get there. Professional facilitation was key to their success, enabling the multidisciplinary bioaerosol community to explore and address these challenges within a focused and productive environment to prioritize themes and agree on action plans for continued momentum following the workshops. These themes were as follows: (1) conceptual model; (2) stakeholder mapping; (3) knowledge transfer; (4) writing project and (5) conference-type event, collectively covering research, knowledge mobilization and networking activities. A subsequent in-person follow-up workshop was held in November 2023. It provided an opportunity to share progress on the five themes, critique what had already been done and act as a launch-pad to progress the actions further. Delegates also had the opportunity to share ongoing or upcoming work, particularly projects requiring input from others, to encourage collaborative working and sharing expertise. The use of facilitated workshops is a valuable tool for all scientific communities to collectively explore and successfully address key issues within their field.

Chemical gradients and the emergence of distinct microenvironments in biofilms are vital to the stratification, maturation and overall function of microbial communities. These gradients have been well characterized throughout the biofilm mass, but the microenvironment of recently discovered nutrient transporting channels in Escherichia coli biofilms remains unexplored. This study employs three different oxygen sensing approaches to provide a robust quantitative overview of the oxygen gradients and microenvironments throughout the biofilm transport channel networks formed by E. coli macrocolony biofilms. Oxygen nanosensing combined with confocal laser scanning microscopy established that the oxygen concentration changes along the length of biofilm transport channels. Electrochemical sensing provided precise quantification of the oxygen profile in the transport channels, showing similar anoxic profiles compared with the adjacent cells. Anoxic biosensing corroborated these approaches, providing an overview of the oxygen utilization throughout the biomass. The discovery that transport channels maintain oxygen gradients contradicts the previous literature that channels are completely open to the environment along the apical surface of the biofilm. We provide a potential mechanism for the sustenance of channel microenvironments via orthogonal visualizations of biofilm thin sections showing thin layers of actively growing cells. This complete overview of the oxygen environment in biofilm transport channels primes future studies aiming to exploit these emergent structures for new bioremediation approaches.