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1.
Trends Ecol Evol ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003192

RESUMEN

Life history strategies, which combine schedules of survival, development, and reproduction, shape how natural selection acts on species' heritable traits and organismal fitness. Comparative analyses have historically ranked life histories along a fast-slow continuum, describing a negative association between time allocation to reproduction and development versus survival. However, higher-quality, more representative data and analyses have revealed that life history variation cannot be fully accounted for by this single continuum. Moreover, studies often do not test predictions from existing theories and instead operate as exploratory exercises. To move forward, we offer three recommendations for future investigations: standardizing life history traits, overcoming taxonomic siloes, and using theory to move from describing to understanding life history variation across the Tree of Life.

2.
PLoS Negl Trop Dis ; 18(7): e0012329, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38990803

RESUMEN

[This corrects the article DOI: 10.1371/journal.pntd.0001331.].

3.
J Nutr ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025332

RESUMEN

BACKGROUND: Pulse ingredients often replace grains in grain-free dog diets due to their high protein content. However, research to ascertain the benefit of this modification is limited. OBJECTIVE: To correlate food compounds in one corn-inclusive control diet (Ctl) and three grain-free diets with increasing inclusions of whole pulses (up to 45%; Pulse15, Pulse30, Pulse45), formulated to meet similar macro and micronutrient targets with postprandial amino acids (AA) in healthy dogs over 20-weeks. METHODS: Diets were analyzed for biochemical compounds using tandem-MS. Twenty-eight outdoor-housed, healthy, adult Siberian Huskies were allocated to diet and meal responses took place at baseline and weeks 2, 4, 8, 16 and 20 with samples collected at fasted and 15, 30, 60, 90, 120 and 180 minutes after meal presentation. Blood AAs were analyzed by UPLC and differences across week, treatment and time post-meal were analyzed in SAS Studio. Partial least squares regression was performed in SAS Studio using biochemical compounds in the diet as predictor variables and blood AAs as response variables. RESULTS: In plasma, Pulse45 had ∼32% greater postprandial Asn compared to Pulse15, and Ctl had ∼34% greater postprandial Leu and ∼35% greater Pro compared to Pulse15 (P < 0.05). In whole blood, Pulse30 had ∼23% greater postprandial Lys compared to Ctl, and Ctl had ∼21% greater postprandial Met and ∼18% greater Pro compared to Pulse45 and Pulse30, respectively (P < 0.05). Several phospholipids were correlated with postprandial AAs. Compounds in the 'urea cycle' and 'glycine and serine metabolism' were more enriched (P < 0.05) in plasma and whole blood, respectively. CONCLUSIONS: In macro and micronutrient balanced canine diets that differ in their inclusion of corn- versus pulse-derived ingredients, postprandial changes in circulating AAs are largely indicative of the dietary AAs. This helps further our understanding of AA metabolism in healthy dogs fed grain-free diets.

4.
Nature ; 631(8021): 544-548, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39020036

RESUMEN

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.


Asunto(s)
Excipientes , Excipientes/química , Proteínas/química , Proteínas/metabolismo , Humanos , Estabilidad Proteica , Liofilización , Hidrogeles/química , Geles/química , Trehalosa/química
5.
Nature ; 631(8022): 808-813, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39020163

RESUMEN

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.


Asunto(s)
Biodiversidad , Biomasa , Conservación de los Recursos Naturales , Agricultura Forestal , Bosques , Clima Tropical , Malasia , Árboles/crecimiento & desarrollo , Animales
6.
Nanoscale ; 16(18): 8922-8930, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591601

RESUMEN

Understanding the key parameters that control the self-assembly process is critical to predict self-assembly modes in multi-component systems, which will lead to the development of nanofibrous materials with tuneable properties. Enantiomeric amino acid-based low-molecular-weight gelators (LMWGs) were mixed in polar (polar protic) and aromatic apolar (aromatic) solvents and compared to their individual counterparts to probe the effect of solvent polarity on the self-assembly process. Scanning electron microscopy (SEM) reveals that xerogels of individual components display hollow needles in polar protic solvents, while chiral coils are observed in aromatic solvents. In contrast, the multi-component gel displays hollow needle morphologies in both solvents, indicating similar morphologies in polar protic solvents but an entirely different nanostructure for the individual gel networks in aromatic solvents. PXRD experiments performed on the dried gels showed that the nature of the solvents plays a vital role in the co-assembly process of multi-component gels. The self-assembly modes and the gel state structure of the gels are analysed by wide-angle X-ray diffraction (WAXS) and small-angle neutron diffraction (SANS), which reveals that the mixed gel undergoes different co-assembly modes depending on the nature of the solvent systems. This study shows that different co-assembly modes can be achieved for structurally similar components by varying the solvent polarity, demonstrating the importance of solvent choice in the self-assembly process of multi-component gels.

7.
ACS Appl Mater Interfaces ; 16(15): 19585-19593, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38579106

RESUMEN

We present the development of time-programmable functional soft materials. The materials undergo reversible phase transitions between lyotropic phases with different topologies and symmetries, which in turn have very different physical properties: viscosity, diffusion, and optical transparency. Here, this behavior is achieved by combining pH-responsive lyotropic phases made from the lipid monoolein doped with 10% oleic acid, with chemical reactions that have well-defined controllable kinetics: autocatalytic urea-urease and methyl formate hydrolysis, which increase and decrease pH, respectively. In this case, we use small-angle X-ray scattering (SAXS) and optical imaging to show temporally controlled transitions between the cloudy hexagonal phase, which is a two-dimensional (2D) array of cylindrical inverse micelles, and the transparent, highly viscous three-dimensional (3D) bicontinuous cubic phases. By combining these into a single reaction mixture where the pH increases and then decreases again, we can induce a sequential transformation cycle from hexagonal to cubic and back to hexagonal over several hours. The sample therefore changes from cloudy to transparent and back again as a proof-of-concept demonstration for a wider range of soft materials with time-programmable changes in physical properties.

8.
Microb Genom ; 10(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38683195

RESUMEN

The advent of viral metagenomics, or viromics, has improved our knowledge and understanding of global viral diversity. High-throughput sequencing technologies enable explorations of the ecological roles, contributions to host metabolism, and the influence of viruses in various environments, including the human intestinal microbiome. However, bacterial metagenomic studies frequently have the advantage. The adoption of advanced technologies like long-read sequencing has the potential to be transformative in refining viromics and metagenomics. Here, we examined the effectiveness of long-read and hybrid sequencing by comparing Illumina short-read and Oxford Nanopore Technology (ONT) long-read sequencing technologies and different assembly strategies on recovering viral genomes from human faecal samples. Our findings showed that if a single sequencing technology is to be chosen for virome analysis, Illumina is preferable due to its superior ability to recover fully resolved viral genomes and minimise erroneous genomes. While ONT assemblies were effective in recovering viral diversity, the challenges related to input requirements and the necessity for amplification made it less ideal as a standalone solution. However, using a combined, hybrid approach enabled a more authentic representation of viral diversity to be obtained within samples.


Asunto(s)
Heces , Microbioma Gastrointestinal , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica/métodos , Microbioma Gastrointestinal/genética , Heces/virología , Heces/microbiología , Nanoporos , Secuenciación de Nanoporos/métodos , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Viroma/genética , Análisis de Secuencia de ADN/métodos
9.
Biomacromolecules ; 25(5): 3169-3177, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38684138

RESUMEN

Achieving precise control over gelator alignment and morphology is crucial for crafting tailored materials and supramolecular structures with distinct properties. We successfully aligned the self-assembled micelles formed by a functionalized dipeptide 2NapFF into long 1-D "gel noodles" by cross-linking with divalent metal chlorides. We identify the most effective cross-linker for alignment, enhancing mechanical stability, and imparting functional properties. Our study shows that Group 2 metal ions are particularly suited for creating mechanically robust yet flexible gel noodles because of their ionic and nondirectional bonding with carboxylate groups. In contrast, the covalent nature and high directional bonds of d-block metal ions with carboxylates tend to disrupt the self-assembly of 2NapFF. Furthermore, the 2NapFF-Cu noodles demonstrated selective antibacterial activity, indicating that the potent antibacterial property of the copper(II) ion is preserved within the cross-linked system. By merging insights into molecular alignment, gel extrusion processing, and integrating specific functionalities, we illustrate how the versatility of dipeptide-based gels can be utilized in creating next-generation soft materials.


Asunto(s)
Antibacterianos , Cobre , Geles , Antibacterianos/química , Antibacterianos/farmacología , Cobre/química , Cobre/farmacología , Geles/química , Reactivos de Enlaces Cruzados/química , Dipéptidos/química , Dipéptidos/farmacología , Micelas , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos
10.
Front Microbiol ; 15: 1361121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633694

RESUMEN

Bacteriophages (phages), viruses that infect bacteria, are found in abundance not only in the environment but also in the human body. The use of phages for the diagnosis of melioidosis, a tropical infectious disease caused by Burkholderia pseudomallei, is emerging as a promising novel approach, but our understanding of conditions under which Burkholderia prophages can be induced remains limited. Here, we first demonstrated the isolation of Burkholderia phages from the hemocultures of melioidosis patients. The B. pseudomallei-positive hemoculture bottles were filtered to remove bacteria, and then phages were isolated and purified by spot and double agar overlay plaque assays. Forty blood samples (hemoculture-confirmed melioidosis) were tested, and phages were found in 30% of the samples. Transmission electron microscopy and genome analysis of the isolated phages, vB_HM387 and vB_HM795, showed that both phages are Myoviruses. These two phages were stable at a pH of 5-7 and temperatures of 25-37°C, suggesting their ability to survive in human blood. The genome sizes of vB_HM387 and vB_HM795 are 36.3 and 44.0 kb, respectively. A phylogenetic analysis indicated that vB_HM387 has homologs, but vB_HM795 is a novel Myovirus, suggesting the heterogeneity of Burkholderia phages in melioidosis patients. The key finding that Burkholderia phages could be isolated from the blood of melioidosis patients highlights the potential application of phage-based assays by detecting phages in blood as a pathogen-derived biomarker of infection.

11.
Cell Rep Phys Sci ; 5(2)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38464674

RESUMEN

Peptide-based biopolymers have gained increasing attention due to their versatile applications. A naphthalene dipeptide (2NapFF) can form chirality-dependent tubular micelles, leading to supramolecular gels. The precise molecular arrangement within these micelles and the mechanism governing gelation have remained enigmatic. We determined, at near-atomic resolution, cryoelectron microscopy structures of the 2NapFF micelles LL-tube and LD-tube, generated by the stereoisomers (l,l)-2NapFF and (l,d)-2NapFF, respectively. The structures reveal that the fundamental packing of dipeptides is driven by the systematic π-π stacking of aromatic rings and that same-charge repulsion between the carbonyl groups is responsible for the stiffness of both tubes. The structural analysis elucidates how a single residue's altered chirality gives rise to markedly distinct tubular structures and sheds light on the mechanisms underlying the pH-dependent gelation of LL- and LD-tubes. The understanding of dipeptide packing and gelation mechanisms provides insights for the rational design of 2NapFF derivatives, enabling the modulation of micellar dimensions.

12.
Emerg Infect Dis ; 30(4): 701-710, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38526070

RESUMEN

Salmonella enterica serovar Infantis presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). We analyzed whole-genome sequences of 5,284 Salmonella Infantis strains from 74 countries, isolated during 1989-2020 from a wide variety of human, animal, and food sources, to compare genetic phylogeny, AMR determinants, and plasmid presence. The global Salmonella Infantis population structure diverged into 3 clusters: a North American cluster, a European cluster, and a global cluster. The levels of AMR varied by Salmonella Infantis cluster and by isolation source; 73% of poultry isolates were multidrug resistant, compared with 35% of human isolates. This finding correlated with the presence of the pESI megaplasmid; 71% of poultry isolates contained pESI, compared with 32% of human isolates. This study provides key information for public health teams engaged in reducing the spread of this pathogen.


Asunto(s)
Salud Única , Salmonella enterica , Animales , Humanos , Serogrupo , Antibacterianos/farmacología , Salmonella/genética , Aves de Corral , Farmacorresistencia Bacteriana Múltiple/genética
13.
PLoS Negl Trop Dis ; 18(2): e0011919, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38354196

RESUMEN

Expanding geographic distribution and increased populations of ticks has resulted in an upsurge of human-tick encounters in the United States (US), leading to an increase in tickborne disease reporting. Limited knowledge of the broadscale spatial range of tick species is heightened by a rapidly changing environment. Therefore, we partnered with the Forest Inventory and Analysis (FIA) program of the Forest Service, U.S. Department of Agriculture and used passive tick surveillance to better understand spatiotemporal variables associated with foresters encountering three tick species (Amblyomma americanum L., Dermacentor variabilis Say, and Ixodes scapularis L.) in the southeastern US. Eight years (2014-2021) of tick encounter data were used to fit environmental niche and generalized linear models to predict where and when ticks are likely to be encountered. Our results indicate temporal and environmental partitioning of the three species. Ixodes scapularis were more likely to be encountered in the autumn and winter seasons and associated with soil organic matter, vegetation indices, evapotranspiration, temperature, and gross primary productivity. By contrast, A. americanum and D. variabilis were more likely to be encountered in spring and summer seasons and associated with elevation, landcover, temperature, dead belowground biomass, vapor pressure, and precipitation. Regions in the southeast least suitable for encountering ticks included the Blue Ridge, Mississippi Alluvial Plain, and the Southern Florida Coastal Plain, whereas suitable regions included the Interior Plateau, Central Appalachians, Ozark Highlands, Boston Mountains, and the Ouachita Mountains. Spatial and temporal patterns of different tick species can inform outdoorsmen and the public on tick avoidance measures, reduce tick populations by managing suitable tick habitats, and monitoring areas with unsuitable tick habitat for potential missed encounters.


Asunto(s)
Ixodes , Animales , Humanos , Estados Unidos/epidemiología , Sudeste de Estados Unidos/epidemiología , Florida/epidemiología , Región de los Apalaches , Amblyomma
14.
Sci Total Environ ; 920: 170984, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38365025

RESUMEN

Exposure to elevated particulate matter (PM) concentrations in ambient air has become a major health concern over urban areas worldwide. Reactive oxygen species (ROS) generation due to ambient PM (termed as their oxidative potential, OP) is shown to play a major role in PM-induced health effects. In the present study, the OP of the ambient PM2.5 samples, collected during summer 2019 from New Delhi, were measured using the dithiothreitol (DTT) assay. Average volume-normalized OP (OPV) was 2.9 ± 1.1 nmol DTT min-1 m-3, and mass-normalized OP (OPm) was 61 ± 29 pmol DTT min-1 µg-1. The regression statistics of OPv vs chemical species show the maximum slope of OPV with the elemental carbon (EC, r2 = 0.72) followed by water-soluble organic carbon (WSOC, r2 = 0.72), and organic carbon (OC, r2 = 0.64). A strong positive correlation between OPm and secondary inorganic aerosols (SIA, such as NH4+ and NO3- mass fractions) was also observed, indicating that the sources emitting NO2 and NH3, precursors of NO3- and NH4+, also emit DTT-active species. Interestingly, the slope value of OPv vs OC for aged aerosols (OM/OC > 1.7, f44 > 0.12 and f43 < 0.04) was 1.7 times higher than relatively fresh organic aerosols (OA, OM/OC < 1.7, f44 < 0.12, f43 > 0.04). An increase in OPv and OPoc with f44 indicates the formation of more DTT active species with the ageing of OA. A linear increase in OPoc with increasing Nitrogen/Carbon (N/C) ratio suggests that nitrogenous OA have higher OP.

15.
Chemistry ; 30(25): e202400544, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38407499

RESUMEN

Light can be used to design stimuli-responsive systems. We induce transient changes in the assembly of a low molecular weight gelator solution using a merocyanine photoacid. Through our approach, reversible viscosity changes can be achieved via irradiation, delivering systems where flow can be controlled non-invasively on demand.

16.
Soft Matter ; 20(5): 1151, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38250961

RESUMEN

Correction for 'Multi-layer 3D printed dipeptide-based low molecular weight gels' by Max J. S. Hill et al., Soft Matter, 2022, 18, 5960-5965, https://doi.org/10.1039/D2SM00663D.

17.
J Extracell Vesicles ; 13(1): e12406, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38240185

RESUMEN

Bacterial extracellular vesicles (BEVs) contribute to stress responses, quorum sensing, biofilm formation and interspecies and interkingdom communication. However, the factors that regulate their release and heterogeneity are not well understood. We set out to investigate these factors in the common gut commensal Bacteroides thetaiotaomicron by studying BEV release throughout their growth cycle. Utilising a range of methods, we demonstrate that vesicles released at different stages of growth have significantly different composition, with early vesicles enriched in specifically released outer membrane vesicles (OMVs) containing a larger proportion of lipoproteins, while late phase BEVs primarily contain lytic vesicles with enrichment of cytoplasmic proteins. Furthermore, we demonstrate that lipoproteins containing a negatively charged signal peptide are preferentially incorporated in OMVs. We use this observation to predict all Bacteroides thetaiotaomicron OMV enriched lipoproteins and analyse their function. Overall, our findings highlight the need to understand media composition and BEV release dynamics prior to functional characterisation and define the theoretical functional capacity of Bacteroides thetaiotaomicron OMVs.


Asunto(s)
Bacteroides thetaiotaomicron , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Lipoproteínas/análisis
18.
Nat Mater ; 23(1): 13-15, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38172550
19.
J Dairy Sci ; 107(1): 342-358, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37690727

RESUMEN

A 305-d lactation followed by a 60-d dry period has traditionally been considered economically optimal, yet dairy cows in modern intensive dairy systems are frequently dried off while still producing significant quantities of milk. Managing cows for an extended lactation has reported production, welfare, and economic benefits, but not all cows are suitable for an extended lactation. Implementation of an extended lactation strategy on-farm could benefit from use of a decision support system, based on a mathematical lactation model, that can identify suitable cows during early lactation that have a high likelihood of producing above a target milk yield (MY) at 305 d in milk (DIM). Therefore, our objectives were (1) to compare the suitability of 3 commonly used lactation models for modeling extended lactations (Dijkstra, Wood, and Wilmink) in primiparous and multiparous cows under a variety of lactation lengths, and (2) to determine the amount of early-lactation daily MY data needed to accurately forecast MY at d 305 by using the most suitable model and determine whether this is sufficient for identifying cows suitable for an extended lactation before the end of a typical voluntary waiting period (50-90 d). Daily MY data from 467 individual Holstein-Friesian lactations (DIM >305 d; 379 ± 65-d lactation length [mean ± SD]) were fitted by the 3 lactation models using a nonlinear regression procedure. The parameter estimates of these models, lactation characteristics (peak yield, time to peak yield, and persistency), and goodness-of-fit were compared between parity and different lactation lengths. The models had similar performance, and differences between parity groups were consistent with previous literature. Then, data from only the first i DIM for each individual lactation, where i was incremented by 30 d from 30 to 150 DIM and by 50 d from 150 to 300 DIM, were fitted by each model to forecast MY at d 305. The Dijkstra model was selected for further analysis, as it had superior goodness-of-fit statistics for i= 30 and 60. The data set was fit twice by the Dijkstra model, with parameter bounds either unconstrained or constrained. The quality of predictions of MY at d 305 improved with increasing data availability for both models and assisting the model fitting procedure with more biologically relevant constraints on parameters improved the predictions, but neither was reliable enough for practical use on-farm due to the high uncertainty of forecasted predictions. Using 90 d of data, the constrained model correctly classified 66% of lactations as being above or below a target MY at d 305 of 25 kg/d, with a probability threshold of 0.95. The proportion of correct classifications became smaller at lower targets of MY at d 305 and became greater when using more lactation days. Overall, further work is required to develop a model that can forecast late-lactation MY with sufficient accuracy for practical use. We envisage that a hybridized machine learning and mechanistic model that incorporates additional historical and genetic information with early-lactation MY could produce meaningful lactation curve forecasts.


Asunto(s)
Lactancia , Leche , Embarazo , Femenino , Bovinos , Animales , Leche/metabolismo , Paridad , Calostro , Probabilidad
20.
Ann Clin Microbiol Antimicrob ; 22(1): 82, 2023 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689686

RESUMEN

BACKGROUND: Egypt has witnessed elevated incidence rates of multidrug-resistant Klebsiella pneumoniae infections in intensive care units (ICUs). The treatment of these infections is becoming more challenging whilst colistin-carbapenem-resistant K. pneumoniae is upsurging. Due to the insufficiently available data on the genomic features of colistin-resistant K. pneumoniae in Egypt, it was important to fill in the gap and explore the genomic characteristics, as well as the antimicrobial resistance, the virulence determinants, and the molecular mechanisms of colistin resistance in such a lethal pathogen. METHODS: Seventeen colistin-resistant clinical K. pneumoniae isolates were collected from ICUs in Alexandria, Egypt in a 6-month period in 2020. Colistin resistance was phenotypically detected by modified rapid polymyxin Nordmann/Poirel and broth microdilution techniques. The isolates susceptibility to 20 antimicrobials was determined using Kirby-Bauer disk diffusion method. Whole genome sequencing and bioinformatic analysis were employed for exploring the virulome, resistome, and the genetic basis of colistin resistance mechanisms. RESULTS: Out of the tested K. pneumoniae isolates, 82.35% were extensively drug-resistant and 17.65% were multidrug-resistant. Promising susceptibility levels towards tigecycline (88.24%) and doxycycline (52.94%) were detected. Population structure analysis revealed seven sequence types (ST) and K-types: ST383-K30, ST147-K64, ST17-K25, ST111-K63, ST11-K15, ST14-K2, and ST525-K45. Virulome analysis revealed yersiniabactin, aerobactin, and salmochelin siderophore systems in ˃ 50% of the population. Hypervirulence biomarkers, iucA (52.94%) and rmpA/A2 (5.88%) were detected. Extended-spectrum ß-lactamase- and carbapenemase-producers accounted for 94.12% of the population, with blaCTX-M-15, blaNDM-5, and blaOXA-48 reaching 64.71%, 82.35%, and 82.35%, respectively. Chromosomal alterations in mgrB (82.35%) were the most prevailing colistin resistance-associated genetic change followed by deleterious mutations in ArnT (23.53%, L54H and G164S), PmrA (11.76%, G53V and D86E), PmrB (11.76%, T89P and T134P), PmrC (11.76%, S257L), PhoQ (5.88%, L322Q and Q435H), and ArnB (5.88%, G47D) along with the acquisition of mcr-1.1 by a single isolate of ST525. CONCLUSIONS: In this study, we present the genotypic colistin resistance mechanisms in K. pneumoniae isolated in Egypt. More effective antibiotic stewardship protocols must be implemented by Egyptian health authorities to restrain this hazard and safeguard the future utility of colistin. This is the first characterization of a complete sequence of mcr-1.1-bearing IncHI2/IncHI2A plasmid recovered from K. pneumoniae clinical isolate belonging to the emerging high-risk clone ST525.


Asunto(s)
Colistina , Klebsiella pneumoniae , Humanos , Colistina/farmacología , Egipto , Klebsiella pneumoniae/genética , Genómica , Unidades de Cuidados Intensivos
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