Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Curr Opin Microbiol ; 75: 102368, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37677865

RESUMO

Infections that involve interkingdom microbial communities, such as those between bacteria and yeast pathogens, are difficult to treat, associated with worse patient outcomes, and may be a source of antimicrobial resistance. In this review, we address co-occurrence and co-infections of Candida albicans and Pseudomonas aeruginosa, two pathogens that occupy multiple infection niches in the human body, especially in immunocompromised patients. The interaction between the pathogen species influences microbe-host interactions, the effectiveness of antimicrobials and even infection outcomes, and may thus require adapted treatment strategies. However, the molecular details of bacteria-fungal interactions both inside and outside the infection sites, are insufficiently characterised. We argue that comprehensively understanding the P. aeruginosa-C. albicans interaction network through integrated systems biology approaches will capture the highly dynamic and complex nature of these polymicrobial infections and lead to a more comprehensive understanding of clinical observations such as reshaped immune defences and low antimicrobial treatment efficacy.


Assuntos
Anti-Infecciosos , Coinfecção , Humanos , Candida albicans , Pseudomonas aeruginosa/genética , Interações entre Hospedeiro e Microrganismos
3.
Nat Commun ; 14(1): 4083, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438338

RESUMO

Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.


Assuntos
Pacientes , Humanos , Resistência Microbiana a Medicamentos/genética
4.
Proc Biol Sci ; 290(2002): 20230965, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37403511

RESUMO

Women are underrepresented in senior academic positions within microbiology globally. Studies show that gender bias affects the progression of women in academia, but there is evidence that improving conscious awareness of bias can improve equity in this regard. Here we analyse the publication data associated with review articles within the microbiology field to investigate the statistical associations with author gender. We analyse the data from review articles published between 2010 and 2022 in three leading microbiology review journals: Nature Reviews Microbiology, Trends in Microbiology and Annual Review of Microbiology. We find a significant association between the gender of the lead author and the gender of co-authors in multi-author publications. Review articles with men lead authors have a significantly reduced proportion of women co-authors compared to reviews with women lead authors. Given the existing differences in the proportions of men and women in lead author positions, this association may have important consequences for the relative visibility of women in microbiology, along with negative impacts on scientific output relating to reduced collaboration diversity.


Assuntos
Autoria , Editoração , Humanos , Masculino , Feminino , Sexismo , Estado de Consciência
5.
Nat Commun ; 13(1): 6523, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36414617

RESUMO

Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients.


Assuntos
Antibacterianos , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Meropeném/farmacologia , Pulmão , Bactérias , Unidades de Terapia Intensiva
6.
Elife ; 112022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943060

RESUMO

Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a 'last line of defence' antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of Escherichia coli to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistance between the chromosomal mutations and a mobile resistance gene. Analysis of public genomic datasets shows that lpxC polymorphisms are common in pathogenic E. coli, including those carrying MCR-1, highlighting the clinical relevance of this interaction. Importantly, lpxC diversity is high in pathogenic E. coli from regions with no history of MCR-1 acquisition, suggesting that pre-existing lpxC polymorphisms potentiated the evolution of high-level colistin resistance by MCR-1 acquisition. More broadly, these findings highlight the importance of standing genetic variation and plasmid/chromosomal interactions in the evolutionary dynamics of antibiotic resistance.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Testes de Sensibilidade Microbiana , Plasmídeos/genética
7.
Microbiology (Reading) ; 168(7)2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35849532

RESUMO

CRISPR-Cas systems provide bacteria with both specificity and adaptability in defence against invading genetic elements. From a theoretical perspective, CRISPR-Cas systems confer many benefits. However, they are observed at an unexpectedly low prevalence across the bacterial domain. While these defence systems can be gained horizontally, fitness costs may lead to selection against their carriage. Understanding the source of CRISPR-related fitness costs will help us to understand the evolutionary dynamics of CRISPR-Cas systems and their role in shaping bacterial genome evolution. Here, we review our current understanding of the potential fitness costs associated with CRISPR-Cas systems. In addition to potentially restricting the acquisition of genetic material that could confer fitness benefits, we explore five alternative biological factors that from a theoretical perspective may influence the fitness costs associated with CRISPR-Cas system carriage: (1) the repertoire of defence mechanisms a bacterium has available to it, (2) the potential for a metabolic burden, (3) larger-scale population and environmental factors, (4) the phenomenon of self-targeting spacers, and (5) alternative non-defence roles for CRISPR-Cas.


Assuntos
Bactérias , Sistemas CRISPR-Cas , Bactérias/genética , Genoma Bacteriano/genética
8.
Annu Rev Virol ; 9(1): 57-78, 2022 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-35584889

RESUMO

Viruses of bacteria (bacteriophages or phage) have broad effects on bacterial ecology and evolution in nature that mediate microbial interactions, shape bacterial diversity, and influence nutrient cycling and ecosystem function. The unrelenting impact of phages within the microbial realm is the result, in large part, of their ability to rapidly evolve in response to bacterial host dynamics. The knowledge gained from laboratory systems, typically using pairwise interactions between single-host and single-phage systems, has made clear that phages coevolve with their bacterial hosts rapidly, somewhat predictably, and primarily by counteradapting to host resistance. Recent advancement in metagenomics approaches, as well as a shifting focus toward natural microbial communities and host-associated microbiomes, is beginning to uncover the full picture of phage evolution and ecology within more complex settings. As these data reach their full potential, it will be critical to ask when and how insights gained from studies of phage evolution in vitro can be meaningfully applied to understanding bacteria-phage interactions in nature. In this review, we explore the myriad ways that phagesshape and are themselves shaped by bacterial host populations and communities, with a particular focus on observed and predicted differences between the laboratory and complex microbial communities.


Assuntos
Bacteriófagos , Ecossistema , Bactérias/genética , Bacteriófagos/genética , Ecologia , Metagenômica
9.
Sci Adv ; 7(31)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34330708

RESUMO

Rhizobia induce nodule formation on legume roots and differentiate into bacteroids, which catabolize plant-derived dicarboxylates to reduce atmospheric N2 into ammonia. Despite the agricultural importance of this symbiosis, the mechanisms that govern carbon and nitrogen allocation in bacteroids and promote ammonia secretion to the plant are largely unknown. Using a metabolic model derived from genome-scale datasets, we show that carbon polymer synthesis and alanine secretion by bacteroids facilitate redox balance in microaerobic nodules. Catabolism of dicarboxylates induces not only a higher oxygen demand but also a higher NADH/NAD+ ratio than sugars. Modeling and 13C metabolic flux analysis indicate that oxygen limitation restricts the decarboxylating arm of the tricarboxylic acid cycle, which limits ammonia assimilation into glutamate. By tightly controlling oxygen supply and providing dicarboxylates as the energy and electron source donors for N2 fixation, legumes promote ammonia secretion by bacteroids. This is a defining feature of rhizobium-legume symbioses.

10.
Nat Commun ; 12(1): 2460, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33911082

RESUMO

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Meropeném/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Seleção Genética/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Humanos , Hidroliases/genética , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Plasmídeos/genética , Porinas/genética , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/imunologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Análise de Sequência de DNA , Choque Hemorrágico/microbiologia
11.
ISME J ; 15(5): 1420-1433, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33349652

RESUMO

CRISPR-Cas systems provide bacteria and archaea with an adaptive immune system that targets foreign DNA. However, the xenogenic nature of immunity provided by CRISPR-Cas raises the possibility that these systems may constrain horizontal gene transfer. Here we test this hypothesis in the opportunistic pathogen Pseudomonas aeruginosa, which has emerged as an important model system for understanding CRISPR-Cas function. Across the diversity of P. aeruginosa, active CRISPR-Cas systems are associated with smaller genomes and higher GC content, suggesting that CRISPR-Cas inhibits the acquisition of foreign DNA. Although phage is the major target of CRISPR-Cas spacers, more than 80% of isolates with an active CRISPR-Cas system have spacers that target integrative conjugative elements (ICE) or the conserved conjugative transfer machinery used by plasmids and ICE. Consistent with these results, genomes containing active CRISPR-Cas systems harbour a lower abundance of both prophage and ICE. Crucially, spacers in genomes with active CRISPR-Cas systems map to ICE and phage that are integrated into the chromosomes of closely related genomes lacking CRISPR-Cas immunity. We propose that CRISPR-Cas acts as an important constraint to horizontal gene transfer, and the evolutionary mechanisms that ensure its maintenance or drive its loss are key to the ability of this pathogen to adapt to new niches and stressors.


Assuntos
Bacteriófagos , Sistemas CRISPR-Cas , Bacteriófagos/genética , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Transferência Genética Horizontal , Pseudomonas aeruginosa/genética
12.
Proc Natl Acad Sci U S A ; 117(38): 23823-23834, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900931

RESUMO

By analyzing successive lifestyle stages of a model Rhizobium-legume symbiosis using mariner-based transposon insertion sequencing (INSeq), we have defined the genes required for rhizosphere growth, root colonization, bacterial infection, N2-fixing bacteroids, and release from legume (pea) nodules. While only 27 genes are annotated as nif and fix in Rhizobium leguminosarum, we show 603 genetic regions (593 genes, 5 transfer RNAs, and 5 RNA features) are required for the competitive ability to nodulate pea and fix N2 Of these, 146 are common to rhizosphere growth through to bacteroids. This large number of genes, defined as rhizosphere-progressive, highlights how critical successful competition in the rhizosphere is to subsequent infection and nodulation. As expected, there is also a large group (211) specific for nodule bacteria and bacteroid function. Nodule infection and bacteroid formation require genes for motility, cell envelope restructuring, nodulation signaling, N2 fixation, and metabolic adaptation. Metabolic adaptation includes urea, erythritol and aldehyde metabolism, glycogen synthesis, dicarboxylate metabolism, and glutamine synthesis (GlnII). There are 17 separate lifestyle adaptations specific to rhizosphere growth and 23 to root colonization, distinct from infection and nodule formation. These results dramatically highlight the importance of competition at multiple stages of a Rhizobium-legume symbiosis.


Assuntos
Rhizobium leguminosarum , Rizosfera , Simbiose/genética , Fabaceae/microbiologia , Genes Bacterianos/genética , Fixação de Nitrogênio/genética , Rhizobium leguminosarum/genética , Rhizobium leguminosarum/fisiologia , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/microbiologia
13.
SAGE Open Med Case Rep ; 8: 2050313X20979207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33403114

RESUMO

Reversible cutaneous hyperpigmentation often occurs in the setting of nutritional deficiencies and protein energy malnourishment, with atypical presentations arising from autoimmune disease. Here, we present a 52-year-old female with hypertension, type 1 diabetes, and Hashimoto's thyroiditis, under the diagnosis of polyglandular autoimmune syndrome type II, referred for evaluation of asymptomatic hyperpigmentation of the palms, soles, hard palate, and tongue for 6 months. The patient underwent a significant work-up, including esophagogastroduodenoscopy, which revealed hypertrophic gastropathy as well as evidence of acquired B12 deficiency secondary to pernicious anemia. The patient was initiated on B12 supplementation, with eventual resolution of mucocutaneous findings.

14.
FEMS Microbiol Rev ; 42(4): 448-461, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672765

RESUMO

The attachment of bacteria to roots constitutes the first physical step in many plant-microbe interactions. These interactions exert both positive and negative influences on agricultural systems depending on whether a growth-promoting, symbiotic or pathogenic relationship transpires. A common biphasic mechanism of root attachment exists across agriculturally important microbial species, including Rhizobium, Agrobacterium, Pseudomonas, Azospirillum and Salmonella. Attachment studies have revealed how plant-microbe interactions develop, and how to manipulate these relationships for agricultural benefit. Here, we review our current understanding of the molecular mechanisms governing plant-microbe root attachment and draw together a common biphasic model.


Assuntos
Bactérias/genética , Bactérias/metabolismo , Raízes de Plantas/microbiologia , Plantas/microbiologia , Interações Hospedeiro-Patógeno/fisiologia , Especificidade da Espécie
15.
J Bacteriol ; 199(1)2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27795326

RESUMO

Insertion sequencing (INSeq) analysis of Rhizobium leguminosarum bv. viciae 3841 (Rlv3841) grown on glucose or succinate at both 21% and 1% O2 was used to understand how O2 concentration alters metabolism. Two transcriptional regulators were required for growth on glucose (pRL120207 [eryD] and RL0547 [phoB]), five were required on succinate (pRL100388, RL1641, RL1642, RL3427, and RL4524 [ecfL]), and three were required on 1% O2 (pRL110072, RL0545 [phoU], and RL4042). A novel toxin-antitoxin system was identified that could be important for generation of new plasmidless rhizobial strains. Rlv3841 appears to use the methylglyoxal pathway alongside the Entner-Doudoroff (ED) pathway and tricarboxylic acid (TCA) cycle for optimal growth on glucose. Surprisingly, the ED pathway was required for growth on succinate, suggesting that sugars made by gluconeogenesis must undergo recycling. Altered amino acid metabolism was specifically needed for growth on glucose, including RL2082 (gatB) and pRL120419 (opaA, encoding omega-amino acid:pyruvate transaminase). Growth on succinate specifically required enzymes of nucleobase synthesis, including ribose-phosphate pyrophosphokinase (RL3468 [prs]) and a cytosine deaminase (pRL90208 [codA]). Succinate growth was particularly dependent on cell surface factors, including the PrsD-PrsE type I secretion system and UDP-galactose production. Only RL2393 (glnB, encoding nitrogen regulatory protein PII) was specifically essential for growth on succinate at 1% O2, conditions similar to those experienced by N2-fixing bacteroids. Glutamate synthesis is constitutively activated in glnB mutants, suggesting that consumption of 2-ketoglutarate may increase flux through the TCA cycle, leading to excess reductant that cannot be reoxidized at 1% O2 and cell death. IMPORTANCE: Rhizobium leguminosarum, a soil bacterium that forms N2-fixing symbioses with several agriculturally important leguminous plants (including pea, vetch, and lentil), has been widely utilized as a model to study Rhizobium-legume symbioses. Insertion sequencing (INSeq) has been used to identify factors needed for its growth on different carbon sources and O2 levels. Identification of these factors is fundamental to a better understanding of the cell physiology and core metabolism of this bacterium, which adapts to a variety of different carbon sources and O2 tensions during growth in soil and N2 fixation in symbiosis with legumes.


Assuntos
Glucose/metabolismo , Oxigênio/farmacologia , Rhizobium leguminosarum/crescimento & desenvolvimento , Ácido Succínico/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Meios de Cultura , Relação Dose-Resposta a Droga , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/fisiologia , Técnicas de Amplificação de Ácido Nucleico , Oxigênio/administração & dosagem , Oxigênio/metabolismo , Rhizobium leguminosarum/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...