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1.
Curr Biol ; 34(8): R328-R330, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38653203

RESUMEN

The mysticetes - baleen whales and their toothed ancestors - have a long evolutionary history that, despite many recent paleontological discoveries, remains highly debated. The description of a new mysticete from the latest Eocene of North America opens promising new research directions.


Asunto(s)
Evolución Biológica , Fósiles , Ballenas , Animales , Diente/anatomía & histología , América del Norte , Filogenia
2.
Anat Rec (Hoboken) ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297482

RESUMEN

The tympanoperiotic complex of a blue whale Balaenoptera musculus is described and compared to the homologous structures in the other extant and fossil baleen whale species. The periotic and the tympanic bulla represent informative anatomical regions in both functional and phylogenetic studies and for this reason a micro-CT scan of the bones was performed in order to better characterize their external aspect and to reconstruct the inner structures. In particular, the cochlea, the semicircular canals and associated portions of the periotic are reconstructed so that these structures may be used in phylogenetic analyses. We observed that the blue whale periotic is characterized by the presence of a strong dorsal protrusion which is posteriorly bordered by a previously undescribed morphological character that we name the posterotransverse fossa. The peculiar shape of the anterior process and the en echelon organization of the posterior foramina of the pars cochlearis are also described and compared. From a phylogenetic perspective, the blue whale is confirmed to be closely related to the fin whale, Balaenoptera physalus, but it is suggested, based on ear bone characters only, that it diverged before the other balaenopterid species in the phylogeny of Balaenopteridae. This placement supports a series of morphological observations suggesting that the extant blue whale was an early-diverging member of Balaenoptera. Our results help to decipher the evolutionary origin of the blue whale, the largest living animal, by allowing new and more detailed morphological analyses of the balaenopterid fossil record.

4.
Children (Basel) ; 10(12)2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38136091

RESUMEN

The effectiveness of probiotics in reducing the incidence of necrotizing enterocolitis has been supported by a very large number of studies. However, the utilization of probiotics in preterm infants remains a topic of debate. This study aims to assess the rate of probiotic use in European neonatal intensive care units (NICUs), compare administration protocols, and identify barriers and concerns associated with probiotic use. An online questionnaire was distributed via email to European NICUs between October 2020 and June 2021. Different questions related to the frequency of probiotic use were proposed. Data on probiotic administration protocols and reasons for non-utilization were collected. The majority of responses were from France and Switzerland, with response rates of 85% and 89%, respectively. A total of 21% of French NICUs and 100% of Swiss NICUs reported routine probiotic use. There was significant heterogeneity in probiotic administration protocols, including variations in probiotic strains, administration, and treatment duration. The main obstacles to routine probiotic use were the absence of recommendations, lack of consensus on strain selection, insufficient scientific evidence, and concerns regarding potential adverse effects. The rate of routine probiotic administration remains low in European NICUs, with heterogeneity among protocols. Further trials are necessary to elucidate optimal treatment modalities and ensure safety of administration.

5.
Zoology (Jena) ; 160: 126108, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37633185

RESUMEN

Directional cranial asymmetry is an intriguing condition that has evolved in all odontocetes which has mostly been associated with sound production for echolocation. In this study, we investigated how cranial asymmetry varies across odontocete species both in terms of quality (i.e., shape), and quantity (magnitude of deviation from symmetry). We investigated 72 species across all ten families of Odontoceti using two-dimensional geometric morphometrics. The average asymmetric shape was largely consistent across odontocetes - the rostral tip, maxillae, antorbital notches and braincase, as well as the suture crest between the frontal and interparietal bones were displaced to the right, whereas the nasal septum and premaxillae showed leftward shifts, in concert with an enlargement of the right premaxilla and maxilla. A clear phylogenetic signal related to asymmetric shape variation was identified across odontocetes using squared-change parsimony. The magnitude of asymmetry was widely variable across Odontoceti, with greatest asymmetry in Kogiidae, Monodontidae and Globicephalinae, followed by Physeteridae, Platanistidae and Lipotidae, while the asymmetry was lowest in Lissodelphininae, Phocoenidae, Iniidae and Pontoporiidae. Ziphiidae presented a wide spectrum of asymmetry. Generalized linear models explaining magnitude of asymmetry found associations with click source level while accounting for cranial size. Using phylogenetic generalized least squares, we reconfirm that source level and centroid size significantly predict the level of cranial asymmetry, with more asymmetric marine taxa generally consisting of bigger species emitting higher output sonar signal, i.e. louder sounds. Both characteristics theoretically support foraging at depth, the former by allowing extended diving and the latter being adaptive for prey detection at longer distances. Thus, cranial asymmetry seems to be an evolutionary pathway that allows odontocetes to devote more space for sound-generating structures associated with echolocation and thus increases biosonar search range and foraging efficiency beyond simple phylogenetic scaling predictions.


Asunto(s)
Ecolocación , Ballenas , Animales , Filogenia , Evolución Biológica , Sonido
6.
Nature ; 620(7975): 824-829, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37532931

RESUMEN

The fossil record of cetaceans documents how terrestrial animals acquired extreme adaptations and transitioned to a fully aquatic lifestyle1,2. In whales, this is associated with a substantial increase in maximum body size. Although an elongate body was acquired early in cetacean evolution3, the maximum body mass of baleen whales reflects a recent diversification that culminated in the blue whale4. More generally, hitherto known gigantism among aquatic tetrapods evolved within pelagic, active swimmers. Here we describe Perucetus colossus-a basilosaurid whale from the middle Eocene epoch of Peru. It displays, to our knowledge, the highest degree of bone mass increase known to date, an adaptation associated with shallow diving5. The estimated skeletal mass of P. colossus exceeds that of any known mammal or aquatic vertebrate. We show that the bone structure specializations of aquatic mammals are reflected in the scaling of skeletal fraction (skeletal mass versus whole-body mass) across the entire disparity of amniotes. We use the skeletal fraction to estimate the body mass of P. colossus, which proves to be a contender for the title of heaviest animal on record. Cetacean peak body mass had already been reached around 30 million years before previously assumed, in a coastal context in which primary productivity was particularly high.


Asunto(s)
Adaptación Fisiológica , Evolución Biológica , Peso Corporal , Fósiles , Ballenas , Animales , Aclimatación , Perú , Ballenas/anatomía & histología , Ballenas/clasificación , Ballenas/fisiología , Tamaño Corporal , Esqueleto , Buceo
7.
Sci Rep ; 13(1): 12316, 2023 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-37516781

RESUMEN

Cats are hypercarnivorous, opportunistic animals that have adjusted to anthropogenic environments since the Neolithic period. Through humans, either by direct feeding and/or scavenging on food scraps, the diet of cats has been enriched with animals that they cannot kill themselves (e.g., large mammals, fish). Here, we conducted carbon and nitrogen stable isotope ratio analysis to reconstruct the diet of medieval cats and investigate cat-human interactions in two medieval harbor sites (Qalhât, Oman and Siraf, Iran). The analysis included 28 cat individuals and 100 associated marine and terrestrial faunal samples pertaining to > 30 taxa. The isotopic results indicate a high marine protein-based diet for the cats from Qalhât and a mixed marine-terrestrial (C4) diet for the cats from Siraf. Cats at these sites most likely scavenged on both human food scraps and refuse related to fishing activities, with differences in the two sites most likely associated with the availability of marine resources and/or the living conditions of the cats. By shedding light on the dietary habits of cats from two medieval harbors in the Arabian Gulf and Gulf of Oman, this study illustrates the potential of stable isotope analysis in reconstructing human-cat interactions in the past.


Asunto(s)
Dieta , Alimentos , Animales , Humanos , Irán , Omán , Isótopos de Nitrógeno , Mamíferos
8.
Emerg Infect Dis ; 29(3): 484-492, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36823023

RESUMEN

The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a ß-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted.


Asunto(s)
Bacteriemia , Infecciones por Campylobacter , Campylobacter , Endocarditis , Humanos , Estudios Retrospectivos , Endocarditis/tratamiento farmacológico , Campylobacter fetus , Infecciones por Campylobacter/tratamiento farmacológico , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Francia , Estudios Multicéntricos como Asunto
9.
Biophys J ; 122(11): 2192-2202, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-36582138

RESUMEN

Remorins are a family of multigenic plasma membrane phosphoproteins involved in biotic and abiotic plant interaction mechanisms, partnering in molecular signaling cascades. Signaling activity of remorins depends on their phosphorylation states and subsequent clustering into nanosized membrane domains. The presence of a coiled-coil domain and a C-terminal domain is crucial to anchor remorins to negatively charged membrane domains; however, the exact role of the N-terminal intrinsically disordered domain (IDD) on protein clustering and lipid interactions is largely unknown. Here, we combine chemical biology and imaging approaches to study the partitioning of group 1 remorin into anionic model membranes mimicking the inner leaflet of the plant plasma membrane. Using reconstituted membranes containing a mix of saturated and unsaturated phosphatidylcholine, phosphatidylinositol phosphates, and sterol, we investigate the clustering of remorins to the membrane and monitor the formation of nanosized membrane domains. REM1.3 promoted membrane nanodomain organization on the exposed external leaflet of both spherical lipid vesicles and flat supported lipid bilayers. Our results reveal that REM1.3 drives a mechanism allowing lipid reorganization, leading to the formation of remorin-enriched nanodomains. Phosphorylation of the N-terminal IDD by the calcium protein kinase CPK3 influences this clustering and can lead to the formation of smaller and more disperse domains. Our work reveals the phosphate-dependent involvement of the N-terminal IDD in the remorin-membrane interaction process by driving structural rearrangements at lipid-water interfaces.


Asunto(s)
Proteínas Portadoras , Proteínas de Plantas , Proteínas Portadoras/metabolismo , Proteínas de Plantas/química , Membrana Celular/metabolismo , Plantas/metabolismo , Membrana Dobles de Lípidos/metabolismo
10.
Biochim Biophys Acta Biomembr ; 1865(1): 184075, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36273540

RESUMEN

Bax is a major player in the mitochondrial pathway of apoptosis, by making the Outer Mitochondrial Membrane (OMM) permeable to various apoptogenic factors, including cytochrome c. In order to get further insight into the structure and function of Bax when it is inserted in the OMM, we attempted to reconstitute Bax in nanodiscs. Cell-free protein synthesis in the presence of nanodiscs did not yield Bax-containing nanodiscs, but it provided a simple way to purify full-length Bax without any tag. Purified wild-type Bax (BaxWT) and a constitutively active mutant (BaxP168A) displayed biochemical properties that were in line with previous characterizations following their expression in yeast and human cells followed by their reconstitution into liposomes. Both Bax variants were then reconstituted in nanodiscs. Size exclusion chromatography, dynamic light scattering and transmission electron microscopy showed that nanodiscs formed with BaxP168A were larger than nanodiscs formed with BaxWT. This was consistent with the hypothesis that BaxP168A was reconstituted in nanodiscs as an active oligomer.


Asunto(s)
Liposomas , Membranas Mitocondriales , Humanos , Proteína X Asociada a bcl-2/metabolismo , Membranas Mitocondriales/metabolismo , Liposomas/química , Mitocondrias/metabolismo , Proteínas Portadoras/metabolismo
11.
J Am Acad Dermatol ; 88(1): 94-100, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-31931082

RESUMEN

BACKGROUND: Severe Hurley stage 1 hidradenitis suppurativa (HS1) is a difficult-to-treat form of the disease. OBJECTIVE: To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily)/moxifloxacin (400 mg once daily)/metronidazole (250-500 mg 3 times daily) (RMoM) treatment strategy in patients with severe HS1. METHODS: Prospective, open-label, noncomparative cohort study in 28 consecutive patients. Nineteen patients were treated for 6 weeks by RMoM, followed by 4 weeks of rifampin/moxifloxacin alone, then by cotrimoxazole after remission. Moxifloxacin was replaced by pristinamycin (1 g 3 times daily) in 9 patients because of contraindications or intolerance. The primary endpoint was a Sartorius score of 0 (clinical remission) at week 12. RESULTS: The median Sartorius score dropped from 14 to 0 (P = 6 × 10-6) at week 12, with 75% of patients reaching clinical remission. A low initial Sartorius score was a prognosis factor for clinical remission (P = .049). The main adverse effects were mild gastrointestinal discomfort, mucosal candidiasis, and asthenia. At 1 year of follow-up, the median number of flares dropped from 21/year to 1 (P = 1 × 10-5). LIMITATIONS: Small, monocentric, noncontrolled study. CONCLUSIONS: Complete and prolonged remission can be obtained in severe HS1 by using targeted antimicrobial treatments.


Asunto(s)
Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Rifampin/efectos adversos , Moxifloxacino/uso terapéutico , Metronidazol/efectos adversos , Estudios Prospectivos , Estudios de Seguimiento , Estudios de Cohortes , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
12.
Nat Commun ; 13(1): 6930, 2022 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-36376306

RESUMEN

Bacterial cell shape is generally determined through an interplay between the peptidoglycan cell wall and cytoplasmic filaments made of polymerized MreB. Indeed, some bacteria (e.g., Mycoplasma) that lack both a cell wall and mreB genes consist of non-motile cells that are spherical or pleomorphic. However, other members of the same class Mollicutes (e.g., Spiroplasma, also lacking a cell wall) display a helical cell shape and kink-based motility, which is thought to rely on the presence of five MreB isoforms and a specific fibril protein. Here, we show that heterologous expression of Spiroplasma fibril and MreB proteins confers helical shape and kinking ability to Mycoplasma capricolum cells. Isoform MreB5 is sufficient to confer helicity and kink propagation to mycoplasma cells. Cryoelectron microscopy confirms the association of cytoplasmic MreB filaments with the plasma membrane, suggesting a direct effect on membrane curvature. However, in our experiments, the heterologous expression of MreBs and fibril did not result in efficient motility in culture broth, indicating that additional, unknown Spiroplasma components are required for swimming.


Asunto(s)
Proteínas Bacterianas , Spiroplasma , Microscopía por Crioelectrón , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Citoesqueleto/metabolismo , Peptidoglicano/metabolismo , Spiroplasma/genética
13.
Sci Rep ; 12(1): 18866, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36344518

RESUMEN

Wild bees are declining, mainly due to the expansion of urban habitats that have led to land-use changes. Effects of urbanization on wild bee communities are still unclear, as shown by contrasting reports on their species and functional diversities in urban habitats. To address this current controversy, we built a large dataset, merging 16 surveys carried out in 3 countries of Western Europe during the past decades, and tested whether urbanization influences local wild bee taxonomic and functional community composition. These surveys encompassed a range of urbanization levels, that were quantified using two complementary metrics: the proportion of impervious surfaces and the human population density. Urban expansion, when measured as a proportion of impervious surfaces, but not as human population density, was significantly and negatively correlated with wild bee community species richness. Taxonomic dissimilarity of the bee community was independent of both urbanization metrics. However, occurrence rates of functional traits revealed significant differences between lightly and highly urbanized communities, for both urbanization metrics. With higher human population density, probabilities of occurrence of above-ground nesters, generalist and small species increased. With higher soil sealing, probabilities of occurrence of above-ground nesters, generalists and social bees increased as well. Overall, these results, based on a large European dataset, suggest that urbanization can have negative impacts on wild bee diversity. They further identify some traits favored in urban environments, showing that several wild bee species can thrive in cities.


Asunto(s)
Ecosistema , Urbanización , Humanos , Abejas , Animales , Ciudades , Densidad de Población , Europa (Continente) , Biodiversidad
14.
J Microbiol Methods ; 201: 106564, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36084763

RESUMEN

BACKGROUND: Salmonella enterica is among the major burdens for public health at global level. Typing of salmonellae below the species level is fundamental for different purposes, but traditional methods are expensive, technically demanding, and time-consuming, and therefore limited to reference centers. Fourier transform infrared (FTIR) spectroscopy is an alternative method for bacterial typing, successfully applied for classification at different infra-species levels. AIM: This study aimed to address the challenge of subtyping Salmonella enterica at O-serogroup level by using FTIR spectroscopy. We applied machine learning to develop a novel approach for S. enterica typing, using the FTIR-based IR Biotyper® system (IRBT; Bruker Daltonics GmbH & Co. KG, Germany). We investigated a multicentric collection of isolates, and we compared the novel approach with classical serotyping-based and molecular methods. METHODS: A total of 958 well characterized Salmonella isolates (25 serogroups, 138 serovars), collected in 11 different centers (in Europe and Japan), from clinical, environmental and food samples were included in this study and analyzed by IRBT. Infrared absorption spectra were acquired from water-ethanol bacterial suspensions, from culture isolates grown on seven different agar media. In the first part of the study, the discriminatory potential of the IRBT system was evaluated by comparison with reference typing method/s. In the second part of the study, the artificial intelligence capabilities of the IRBT software were applied to develop a classifier for Salmonella isolates at serogroup level. Different machine learning algorithms were investigated (artificial neural networks and support vector machine). A subset of 88 pre-characterized isolates (corresponding to 25 serogroups and 53 serovars) were included in the training set. The remaining 870 samples were used as validation set. The classifiers were evaluated in terms of accuracy, error rate and failed classification rate. RESULTS: The classifier that provided the highest accuracy in the cross-validation was selected to be tested with four external testing sets. Considering all the testing sites, accuracy ranged from 97.0% to 99.2% for non-selective media, and from 94.7% to 96.4% for selective media. CONCLUSIONS: The IRBT system proved to be a very promising, user-friendly, and cost-effective tool for Salmonella typing at serogroup level. The application of machine learning algorithms proved to enable a novel approach for typing, which relies on automated analysis and result interpretation, and it is therefore free of potential human biases. The system demonstrated a high robustness and adaptability to routine workflows, without the need of highly trained personnel, and proving to be suitable to be applied with isolates grown on different agar media, both selective and unselective. Further tests with currently circulating clinical, food and environmental isolates would be necessary before implementing it as a potentially stand-alone standard method for routine use.


Asunto(s)
Salmonella enterica , Agar , Inteligencia Artificial , Técnicas de Tipificación Bacteriana/métodos , Medios de Cultivo , Etanol , Humanos , Aprendizaje Automático , Salmonella , Serogrupo , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Agua
15.
PeerJ ; 10: e13940, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36157061

RESUMEN

The modern walrus Odobenus rosmarus is characterized by marked sexual dimorphism, related to its polygynous behavior and the aggressive competition between males during the breeding season. Previous studies treated skeletal sexual dimorphism in walruses either qualitatively or with basic quantitative measurements. The present study combines a detailed qualitative comparison of male and female walrus mandibles with quantitative two-dimensional geometric morphometrics analysis (principal component analysis, Procrustes ANOVA and a linear discriminant analysis). In addition to identifying previously recognized sexually dimorphic features (e.g., convexity of the anterior margin of the mandible in adult males), our study finds new morphological differences between males and females, such as a relative dorsal expansion of the anterior part of the mandible and an accentuated concavity between the dorsal margin and the coronoid process in adult males. Both our qualitative comparisons and quantitative analyses demonstrate that sexual dimorphism as expressed in the mandible of extant walruses is statistically significant and that (variation in) mandibular morphology can be used as tool to attribute sex with a good degree of accuracy to isolated mandibles or skeletons lacking the cranium. Sexual dimorphism in walruses is directly related to their sexual behavior, characterized as aggressive in males and linked to a polygynous reproduction system. Indeed, the difference in size of the tusks between males and females but also the use of these during intraspecific fights, can reasonably account for this great mandibular morphological disparity between adult males and females, but also among different ontogenetic stages. Finally, the results obtained in the present study may serve as a starting point for assessing sexual dimorphism more in-depth and studying inter- and intraspecific variation in the mandibles of fossil walruses by identifying quantified size and shape mandibular features.


Asunto(s)
Diente , Morsas , Animales , Masculino , Femenino , Caracteres Sexuales , Mandíbula/anatomía & histología , Cráneo/anatomía & histología , Diente/anatomía & histología
16.
PLoS One ; 17(8): e0273122, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35960760

RESUMEN

Narwhals and belugas are toothed whales belonging to the Monodontidae. Belugas have a circumpolar Arctic and sub-Artic distribution while narwhals are restricted to the Atlantic Arctic. Their geographical ranges overlap during winter migrations in the Baffin Bay area (Canada/West Greenland) and successful interbreeding may occur. Here, we employed geometric morphometrics on museum specimens to explore the cranium and mandible morphology of a known hybrid (NHMD MCE 1356) and the cranium morphology of a putative hybrid (NHMD 1963.44.1.4) relative to skull morphological variation in the parental species. Specifically, we used 3D models of skulls from 69 belugas, 86 narwhals, and the two known/putative hybrids and 2D left hemi-mandibles from 20 belugas, 64 narwhals and the known hybrid. Skull shape analyses allowed clear discrimination between species. Narwhals are characterised by a relatively short rostrum and wide neurocranium while belugas show a more elongated and narrower cranium. Sexual size dimorphism was detected in narwhals, with males larger than females, but no sexual shape dimorphism was detected in either species (excluding presence/absence of tusks in narwhals). Morphological skull variation was also dependent on different allometric slopes between species and sexes in narwhals. Our analyses showed that the cranium of the known hybrid was phenotypically close to belugas but its 2D hemi-mandible had a narwhal shape and size morphology. Both cranium and mandible were strongly correlated, with the pattern of covariation being similar to belugas. The putative hybrid was a pure male narwhal with extruded teeth. Comparison of genomic DNA supported this result, and stable carbon and nitrogen isotope values suggested that the putative hybrid had a more benthic foraging strategy compared to narwhals. This work demonstrates that although the known hybrid could be discriminated from narwhals and belugas, detection of its affinities with these parental species was dependent on the part of the skull analysed.


Asunto(s)
Ballena Beluga , Animales , Cetáceos , Femenino , Gelatina , Masculino , Fenotipo , Cráneo
17.
Antibiotics (Basel) ; 11(2)2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35203729

RESUMEN

Tripartite multidrug RND efflux systems made of an inner membrane transporter, an outer membrane factor (OMF) and a periplasmic adaptor protein (PAP) form a canal to expel drugs across Gram-negative cell wall. Structures of MexA-MexB-OprM and AcrA-AcrB-TolC, from Pseudomonas aeruginosa and Escherichia coli, respectively, depict a reduced interfacial contact between OMF and PAP, making unclear the comprehension of how OMF is recruited. Here, we show that a Q93R mutation of MexA located in the α-hairpin domain increases antibiotic resistance in the MexAQ93R-MexB-OprM-expressed strain. Electron microscopy single-particle analysis reveals that this mutation promotes the formation of tripartite complexes with OprM and non-cognate components OprN and TolC. Evidence indicates that MexAQ93R self-assembles into a hexameric form, likely due to interprotomer interactions between paired R93 and D113 amino acids. C-terminal deletion of OprM prevents the formation of tripartite complexes when mixed with MexA and MexB components but not when replacing MexA with MexAQ93R. This study reveals the Q93R MexA mutation and the OprM C-terminal peptide as molecular determinants modulating the assembly process efficacy with cognate and non-cognate OMFs, even though they are outside the interfacial contact. It provides insights into how OMF selectivity operates during the formation of the tripartite complex.

18.
Antimicrob Agents Chemother ; 66(2): e0158121, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-34807755

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the need for broad-spectrum antivirals against coronaviruses (CoVs). Here, pheophorbide a (Pba) was identified as a highly active antiviral molecule against human CoV-229E after bioguided fractionation of plant extracts. The antiviral activity of Pba was subsequently shown for SARS-CoV-2 and Middle East respiratory syndrome coronavirus (MERS-CoV), and its mechanism of action was further assessed, showing that Pba is an inhibitor of coronavirus entry by directly targeting the viral particle. Interestingly, the antiviral activity of Pba depends on light exposure, and Pba was shown to inhibit virus-cell fusion by stiffening the viral membrane, as demonstrated by cryoelectron microscopy. Moreover, Pba was shown to be broadly active against several other enveloped viruses and reduced SARS-CoV-2 and MERS-CoV replication in primary human bronchial epithelial cells. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity that holds potential for COVID-19 therapy or disinfection of SARS-CoV-2-contaminated surfaces.


Asunto(s)
Productos Biológicos , COVID-19 , Coronavirus del Síndrome Respiratorio de Oriente Medio , Antivirales/farmacología , Productos Biológicos/farmacología , Microscopía por Crioelectrón , Humanos , SARS-CoV-2
19.
Clin Infect Dis ; 75(4): 702-709, 2022 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-34849656

RESUMEN

BACKGROUND: Campylobacter spp. bacteremia is a severe infection. A nationwide 5-year retrospective study was conducted to characterize its clinical features and prognostic factors. METHODS: The study included patients with Campylobacter spp. bacteremia diagnosed in 37 French hospitals participating in the surveillance network of the National Reference Center for Campylobacters and Helicobacters, from 1 January 2015 to 31 December 2019. The goal was to analyze the effects of a delay of appropriate antibiotic therapy and other risk factors on 30-day mortality rates, antibiotic resistance, patient characteristics, and prognosis according to the Campylobacter species. RESULTS: Among the 592 patients, Campylobacter jejuni and Campylobacter fetus were the most commonly identified species (in 42.9% and 42.6%, respectively). The patients were elderly (median age 68 years), and most had underlying conditions, mainly immunodepression (43.4%), hematologic cancers (25.9%), solid neoplasms (23%), and diabetes (22.3%). C. jejuni and Campylobacter coli were associated with gastrointestinal signs, and C. fetus was associated with secondary localizations. Among the 80 patients (13.5%) with secondary localizations, 12 had endocarditis, 38 vascular, 24 osteoarticular, and 9 ascitic fluid infections. The 30-day mortality rate was 11.7%, and an appropriate antibiotic treatment was independently associated with 30-day survival (odds ratio, 0.47 [95% confidence interval, .24-.93]; P = .03). The median efficient therapy initiation delay was quite short (2 days [interquartile range, 0-4 days]) but it had no significant impact on the 30-day mortality rate (P = .78). CONCLUSIONS: Campylobacter spp. bacteremia mainly occurred in elderly immunocompromised individuals with variable clinical presentations according to the species involved. Appropriate antimicrobial therapy was associated with improved 30-day survival.


Asunto(s)
Bacteriemia , Infecciones por Campylobacter , Campylobacter jejuni , Campylobacter , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Infecciones por Campylobacter/tratamiento farmacológico , Infecciones por Campylobacter/epidemiología , Humanos , Estudios Retrospectivos
20.
Curr Biol ; 32(1): 248-255.e2, 2022 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-34813730

RESUMEN

Pachyosteosclerosis-a condition that creates dense, bulky bones-often characterizes the early evolution of secondarily aquatic tetrapods like whales and dolphins1-3 but then usually fades away as swimming efficiency increases.4 Here, we document a remarkable reversal of this pattern, namely the convergent re-emergence of bone densification in Miocene seals, dolphins, and whales from the epicontinental Paratethys Sea of eastern Europe and central Asia. This phenomenon was driven by imbalanced remodeling and inhibited resorption of primary trabeculae and coincided with hypersaline conditions-the Badenian salinity crisis-that affected the Central Paratethys between 13.8 and 13.4 Ma.5 Dense bones acting as ballast would have facilitated efficient swimming in the denser and more buoyant water and hence were likely adaptive in this setting. From the Central Paratethys, pachyosteosclerosis subsequently spread eastward, where it became a defining feature of the endemic late Miocene whale assemblage.6,7.


Asunto(s)
Phocidae , Ballenas , Animales , Huesos , Natación
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