MacNeil, A. | bioRxiv Science

bioRxiv2026

Maximum Unified Fatty Acid Signature Analysis: a new approach to QFASA

Accurately estimating predator diets is crucial for understanding and predicting ecosystem changes. The desire for non-lethal but accurate diet estimation techniques has led to new approaches such as quantitative fatty acid signature analysis (QFASA), a now widely accepted method for estimating the diets of marine predators. We propose a novel alternative to QFASA, namely maximum unified fatty acid signature analysis (MUFASA), to estimate dietary proportions using fatty acid signatures. MUFASA is based on maximum likelihood estimation principles and consequently offers several theoretical advantages over QFASA, including estimates that possess desirable properties when model assumptions hold. In addition, the availability of a likelihood function enables the use of a broad range of existing methodologies that may have the capacity to address current well-known challenges associated with diet estimation via fatty acids. MUFASA and QFASA are compared using simulations based on wide-ranging diets, as well as real-life data from a captive study of harbour seals, for which diets are known. Estimates derived from QFASA and MUFASA are similar, suggesting that diet estimation in this context can potentially be viewed through an MLE framework. While not the primary focus of this work, bootstrap confidence intervals are also developed and preliminary results yield high coverage probabilities when the diet proportions are not near 0 or 1.

ecology↗

bioRxiv2023

A Modified BPaL Regimen for Tuberculosis Treatment replaces Linezolid with Inhaled Spectinamides

The Nix-TB clinical trial evaluated a new 6-month regimen containing three-oral- drugs; bedaquiline (B), pretomanid (Pa) and linezolid (L) (BPaL regimen) for treatment of tuberculosis (TB). This regimen achieved remarkable results as almost 90% of the multidrug resistant (MDR) or extensively drug resistant (XDR) TB participants were cured but many patients also developed severe adverse events (AEs). The AEs were associated with the long-term administration of the protein synthesis inhibitor linezolid. Spectinamide 1599 is also a protein synthesis inhibitor of Mycobacterium tuberculosis with an excellent safety profile but which lacks oral bioavailability. Here, we propose to replace L in the BPaL regimen with spectinamide (S) administered via inhalation and we demonstrate that inhaled spectinamide 1599, combined with BPa --BPaS regimen--has similar efficacy to that of BPaL regimen while simultaneously avoiding the L-associated AEs. The BPaL and BPaS regimens were compared in the BALB/c and C3HeB/FeJ murine chronic TB efficacy models. After 4-weeks of treatment, both regimens promoted equivalent bactericidal effect in both TB murine models. However, treatment with BPaL resulted in significant weight loss and the complete blood count suggested development of anemia. These effects were not similarly observed in mice treated with BPaS. BPaL and BPa, but no the BPaS treatment, also decreased myeloid to erythroid ratio suggesting the S in the BPaS regimen was able to recover this effect. Moreover, the BPaL also increased concentration of proinflammatory cytokines in bone marrow compared to mice receiving BPaS regimen. During therapy both regimens improved the lung lesion burden, reduced neutrophil and cytotoxic T cells counts while increased the number of B and helper and regulatory T cells. These combined data suggest that inhaled spectinamide 1599 combined with BPa is an effective TB regimen that avoids L-associated AEs. IMPORTANCETuberculosis (TB) is an airborne infectious disease that spreads via aerosols containing Mycobacterium tuberculosis (Mtb), the causative agent of TB. TB can be cured by administration of 3-4 drugs for 6-9 months but there are limited treatment options for patients infected with multidrug (MDR) and extensively resistant (XDR) strains of Mtb. BPaL is a new all-oral combination of drugs consisting of Bedaquiline (B), Pretomanid (Pa) and Linezolid (L). This regimen was able to cure [~]90% of MDR and XDR TB patients in clinical trials but many patients developed severe adverse events (AEs) associated to the long-term administration of linezolid. We evaluated a new regimen in which Linezolid in the BPaL regimen was replaced with inhaled spectinamide 1599. In the current study, we demonstrate that 4-weeks of treatment with inhaled spectinamide 1599 in combination with Bedaquiline and Pretomanid has equivalent efficacy to the BPaL drug combination and avoids the L-associated-AEs.

microbiology↗