Search bioRxiv⌕ Search

Biology subjects

Goncalves, L.

Publications and source records attributed to Goncalves, L..

4 recordsLinked to original sources

Emergence of plasmid-borne erm(55)-associated macrolide resistance in Mycobacterium chelonae and other rapidly-growing non-tuberculous mycobacteria in Europe

Macrolides are key agents for treating infections caused by non-tuberculous mycobacteria (NTM). Nevertheless, chromosomal erm genes conferring inducible macrolide resistance are described in some NTM species, such as Mycobacterium abscessus and M. fortuitum, whereas M. chelonae had long been considered as lacking a functional erm. Recent descriptions from the USA and Japan of a new plasmid-borne erm(55) (erm(55)P) in M. chelonae and other rapidly growing mycobacteria (RGM) have challenged this assumption. We investigated erm(55)P occurrence in clinical RGM referred to the French National Reference Centre for Mycobacteria between 2012 and 2026 by genome screening and erm(55)P specific real-time PCR. Positive isolates underwent long-read whole genome sequencing (GridIon, Oxford Nanopore Technologies). Clarithromycin (CLR) minimum inhibitory concentration (MIC) was determined by broth microdilution (RAPMYCO and FRATMYC, Thermo Fisher) and read up to 14 days. Five clinical isolates showing inducible CLR resistance (MIC range <0.25-64 mg/L on day 3-4 and 128- >128 mg/L on day 14) were positive for erm(55)P: one M. chelonae, three M. neoaurum, and one M. parafortuitum. erm(55)P-positive M. chelonae genomes from this and previous descriptions did not cluster together in the phylogenetic analysis of 263 genomes. The assembled plasmids showed high similarity to previously reported erm(55)-carrying plasmids, especially within the erm(55)P region. The upstream sequence of erm(55)P showed a secondary structure compatible with a possible translation attenuation mechanism. These findings document the first report of a plasmid-borne erm(55) in Europe in M. chelonae and other RGM and raise concern about the emergence of plasmid macrolide resistance in NTM.

microbiology↗

BODIPY-Tagged β-Lactams as Selective Quenched Activity-Based Probes to Target Human Neutrophil Elastase

Activity-based probes are indispensable tools for interrogating protease function, and quenched fluorescent variants enable dynamic, real-time imaging of enzymatic activity. Despite these advances, very few quenched activity-based probes (qABPs) have been reported for serine proteases, which constitute the largest and most diverse mechanistic class of proteases. {beta}-Lactams have been extensively used to develop molecular tools and drugs designed to bind or be hydrolysed by serine-dependent bacterial enzymes. Here, we report the first monocyclic {beta}-lactam-containing qABPs for detecting serine proteases. Both the enzyme-triggered activation mechanism and intrinsic reactivity of the probes were highly dependent on the relative position of the BODIPY-FL fluorophore and quencher moiety at the {beta}-lactam core. qABPs displaying the most efficient turn-on mechanism were shown to selectively target human neutrophil elastase (HNE) in different human cell lysates. The most successful qABP was rapidly internalised and targeted HNE in U937 cells and human neutrophils. These results demonstrate the potential of the modular {beta}-lactam warhead to develop turn-on probes to track neutrophil serine proteases in live cells

pharmacology and toxicology↗

Warmer climate threatens the occurrence of giant trees in the Amazon basin

Giant trees in the Amazon play crucial ecological roles by acting as substantial carbon sinks and supporting diverse forest ecosystems. However, these emergent trees are increasingly vulnerable to climatic changes, and recent research suggests that the distribution and niche of many emergent species are severely threatened. This study employs ecological niche modeling using data LiDAR and forest inventory, global repository data, and bioclimatic variables to project the potential larger tree distributions under past, current, and future climate scenarios (SSP1-2.6 and SSP5-8.5) in different biogeographic provinces in the Amazon basin. We used algorithms MARS, RandomForest, MaxEnt, and GAM to assess the impact of critical climatic factors, including isothermality, maximum temperatures, and precipitation patterns, on the habitat suitability of these larger trees and species Dinizia excelsa and Goupia glabra. Our results show that the tall trees dataset, Dinizia excelsa and Goupia glabra exhibit congruent distinct responses to climate variables, with Dinizia excelsa being more sensitive to increased temperature extremes, particularly in the Guiana Shield and Roraima Provinces. In contrast, Goupia glabra displays a broader tolerance to precipitation variability. Under the high-emission scenario (SSP5-8.5), both species are projected to lose up to 45% of their suitable habitats by 2080, primarily in southern Amazon provinces like Xingu-Tapajos, where increased drought frequency and temperature extremes are expected. Conversely, the low-emission scenario (SSP1-2.6) suggests potential habitat stability or even slight expansions in the northern Amazon regions due to moderate temperature and rainfall conditions. These findings highlight the urgent need for conservation strategies to protect critical refugia and enhance ecosystem resilience. By integrating niche modeling with climate projections, our study provides vital insights into managing Amazonian giant trees, emphasizing their potential role in mitigating global climate change impacts.

ecology↗

What is known about modified insects for disease prevention?: a systematic review

The modification and release of insects to suppress or replace natural insect vectors constitutes a promising tool for vector control and disease prevention, facing the unprecedented global emergence of vector-borne diseases. Little is known regarding these innovative modification strategies and available evidence is not standardized turning it difficult to reflect on their actual efficacy and eventual effects.\n\nThis work conducted a systematic review, gathering and analyzing research articles from PubMed and Biblioteca Virtual em Saude databases whose results directly report efficacy and effects of the use of modified insects for disease prevention until 2016. Within more than 1500 publications that were screened a total of 349 where analyzed.\n\nA total of 12/3.4% reported field-based evidence, and 41/11.7% covered modification stretagies efficacy after insects release, their epidemiology impact or its long-term efficacy. Examples of successful results were the replacement of natural field populations by wolbachia-infected mosquitoes in 5 weeks, and the elimination of a population in laboratory cages after transgenic mosquitoes release over 10-20 weeks. Variability in the effective results were described (90/25.7%) questioning its reproducibility in different settings. We also found 38/10.9% publications reporting reversal outcomes, such as an increase of vector population after release. Ecological effects such as horizontal transfer events to non-target species (54/15.5%), and wolbachia-induced worsening pathogenesis on mammal filarial diseases (10/2.9%) were also reported.\n\nPresent work revealed promising outcomes of both suppressing and replacing approaches. However, it also revealed a need of field-based evidence mainly regarding epidemiologic and long-term impact of insect modification strategies. It pointed out some eventual irreversible and important effects that must not be ignored when considering open-field releases, and that may constitute constraints to generate the missing field evidence. Moreover, the level of variability of existing evidence suggests the need of local/specific evidence in each setting of an eventual release.\n\nAuthor summaryInnovative strategies are needed to arrest the unprecedented increase of vector-borne disease incidence, distribution and severity. Several modification techniques are being tried all over the world. However this is still an emergent topic with scarce available information and of complex understanding.\n\nPresent work is the unique structured review regarding the use of modified insects for vector-borne disease prevention, bringing neutral and robust evidence that will contribute with critical insights regarding these approaches.\n\nHere we explored more than 1200 publications and analyzed 349 publications on this subject, describing the actual efficacy and reported effects of several modification strategies. More than 30 categories were reported such as, the type of modification, the year of the publication, the species were results were tested, the type of study, and also type of Efficacy Outcome (from modification to long-term) and/or the type of Effects Outcome (from physiologic to ecologic effects). Analysis revealed promising outcomes regarding vector-control and disease prevention. However insects modification strategies still lack field-based evidence mainly regarding epidemiological and long-term efficacy. Eventual reversal outcomes on disease transmission, or irreversible biological effects (including horizontal transfer to non-target species or worsening pathogenesis in particular diseases in mammals), were also described. These effects need to be explored, dispelled or resolved before field trials occur in human residential areas. Some of these questions could only have a robust answer if these strategies would be implemented, needing to take the risk to observe reversal outcomes and/or irreversible effects. These findings reflect the big dilemma that is under the use of modified insects to prevent vector-borne diseases. Findings could support health authorities in decision-making and regulatory committees during advisory processes, by evaluating the pros/cons of each modifying technique for a particular setting. Moreover they could also summarize what is crucial to inform to communities if planning open field releases in residential areas.

ecology↗