Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.01.26.701284

Understanding the role of membrane lipids in mechanism of antimicrobial photodynamic therapy in Escherichia coli

Piksa, M.·Bromke, M. A.·Marques, C. M.·Lecuyer, S.·Daira, P.·Fourmaux, B.·Samuel, I. D. W.·Matczyszyn, K.·Pawlik, K. J.
View original source ↗Export metadata ↓

Abstract

Antimicrobial photodynamic therapy (aPDT) is a promising alternative to antibiotics, yet the molecular factors determining bacterial susceptibility remain unclear. This study investigates the critical role of bacterial lipids, particularly cardiolipin (CL) in the aPDT response of Escherichia coli using methylene blue as a photosensitizer. Through genetic deletion ({Delta}clsABC) and chemical modification via mannitol supplementation, we demonstrate that reduced CL levels significantly enhance bacterial sensitivity, leading to an additional reduction in viability exceeding 3 log10. Quantitative lipidomics (MS,GC) confirmed substantial CL depletion and altered fatty acid saturation. Interestingly, while live CL-deficient cells were more vulnerable, biomimetic giant unilamellar vesicles (GUVs) with higher CL content showed greater susceptibility to photo-oxidation. These findings suggest that CL-rich microdomains in living bacteria act as functional scaffolds for stress-defense systems rather than mere targets for oxidative damage. Modulating membrane lipid composition thus represents a novel strategy to potentiate aPDT efficacy.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Piksa, M., Bromke, M. A., Marques, C. M., Lecuyer, S., Daira, P., Fourmaux, B., Samuel, I. D. W., Matczyszyn, K., Pawlik, K. J.. 2026-01-26. Understanding the role of membrane lipids in mechanism of antimicrobial photodynamic therapy in Escherichia coli. https://doi.org/10.64898/2026.01.26.701284

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Biogenic flavonoid capping converts a cytotoxic Carica papaya fraction into a selective, cross-serotype Dengue entry inhibitor

Plant-derived flavonoids show measurable anti-dengue activity in cell culture, but their translational value is limited by a narrow therapeutic window: the concentrations that inhibit the virus approach or exceed those that are cytotoxic. Whether nanoparticle formulation can resolve this constraint, rather than simply add potency, remains untested for a chemically defined fraction. Here we show that biogenic silver nanoparticle (AgNP) formation using a flavonoid-enriched fraction of Carica papaya inverts an unusable selectivity profile into a viable one. The unformulated fraction was cytotoxic below the concentrations required for antiviral activity: its 50% cytotoxic concentration (CC50 = 134.9 ug/mL) lay below its 50% effective concentration against dengue virus serotype 2 (DENV-2; EC50 = 254.4 ug/mL), giving a Selectivity Index (SI) of 0.53. Using the same flavonoids as sole reducing and capping agents produced AgNPs (Z-average 128.4 nm; PDI 0.232; zeta potential -28.4 mV) that moved both parameters simultaneously. CC50 rose approximately 8.6-fold to 1,165.74 ug/mL while EC50 fell approximately 8.8-fold to 29.05 ug/mL, raising the SI to 40.12, an approximately 75-fold shift. Time-of-addition analysis localised the effect to the extracellular phase: inhibition was significant under pre-treatment and co-treatment but not after viral adsorption, identifying the AgNPs as entry inhibitors rather than replication inhibitors. Consistent with a serotype-independent physical mechanism, AgNP treatment at 30 ug/mL reduced viral RNA across all four serotypes, using inocula standardised against WHO-traceable NAAT reference reagents. These findings identify capping chemistry, rather than silver content alone, as a determinant of the therapeutic window in phytosynthesised nanoantivirals.

microbiology↗
bioRxiv2026

Development of lyophilized faecal inoculation capsules for use in koala rehabilitation and conservation

As a specialist herbivore, koalas rely on their gut microbiomes to help digest their toxic and fibrous diet of Eucalyptus leaves. Without these critical microbes, koalas may not be able to obtain the nutrients and energy they need to survive. As such, a large proportion of koalas that undergo rehabilitation for chlamydiosis develop gut dysbiosis from the antibiotic treatment and are either euthanized or die. Here we aimed to modify previously developed fresh faecal inoculation capsules for an extended shelf-life such that they could be applied in a clinical setting to prevent or treat gut dysbiosis. Using 16S rRNA gene amplicon sequencing we demonstrated that air-drying faecal material leads to an overgrowth of facultative anaerobes, whereas lyophilised material retains a similar microbial composition to fresh material. Initial survival of koala faecal microbes as assessed by live/dead staining combined with microscopy was high after lyophilisation regardless of which excipient was used, except for 20% glycerol that resulted in ~15% lower survival than other treatments. Lyophilised fine particles extracted from koala faeces and packaged into acid-resistant capsules maintained their original microbial composition and had high microbial survival over a year, regardless of the excipient used. Dry-fill, single-layer capsules maintained integrity after 10 hrs in synthetic koala stomach acid. These capsules may be useful in adapting the gut microbiomes of koalas to novel diets e.g. during translocations. However, attempts to apply the capsules in the clinical setting were unsuccessful due to unanticipated difficulties in administrating the capsules to sick koalas.

microbiology↗
bioRxiv2026

The two-component microbial system of the black soldier fly larvae (BSFL) gut: a plastic microbiota in the midgut, but a stable one in the hindgut

Due to their highly polyphagous capacities, black soldier fly (Hermetia illucens) larvae (BSFL) are increasingly valued for their ability to convert organic waste into valuable biomass that can be used for a variety of purposes. These remarkable digestive capabilities are highly dependent on an extremely plastic gut microbiota. However, the distribution and functioning of bacterial communities in the various gut compartments - particularly in the hindgut - remain little understood. In this study, we used a metabarcoding approach based on 16S gene sequencing to investigate the effect of three carbohydrate-rich diets with distinct molecular compositions on the functional diversity of the BSFL gut microbiota. Our results showed that the midgut harbors a highly substrate-sensitive microbiota, with a high abundance of Actinomyces spp., regardless of the substrate. A bacterial diversity oriented toward fatty acid biosynthesis pathways is promoted by starch-rich environment, whereas a lignocellulosic substrate fosters a midgut microbiota dominated by Paenibacillus spp. In contrast, the hindgut exhibits a distinctly stable and homogeneous bacterial composition dominated by Dysgonomonas spp. Overall, our results provide clear evidence of a two-compartment microbial system, in which the midgut primarily serves as a substrate-adaptive primary degradation chamber, while the hindgut functions as a stable terminal compartment for the final processing of residual substrates and the recycling of nutrients. These findings contribute to our understanding of the functional diversity of the bacterial microbiota along the BSFL digestive tract, which is a key factor in explaining this insect's remarkable polyphagous behavior and optimizing its use for industrial purposes.

microbiology↗