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1.
Diagn Microbiol Infect Dis ; 108(2): 116137, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134822

RESUMO

Sarcina ventriculi, also known as Zymosarcina ventriculi and, incorrectly, as Clostridium ventriculi, is rarely encountered in clinical settings. A patient with a complicated gastrointestinal (GI) history, who was acutely presenting with small-bowel obstruction, was found to be colonized by S. ventriculi. The distinctive morphology of this species, with large Gram-variable cocci (up to 3 µm) arranged in two-by-two cuboid clusters reaching up to 20 µm, was key in identifying this bacterium in a stomach biopsy specimen. Sarcina ventriculi appears to be ubiquitously found in nature, and related bacterial species can cause GI-related disease in various animals. Clinical manifestations in humans are broad and often related to other underlying comorbidities. Isolation of S. ventriculi in the laboratory requires anaerobic culture on select media but its absence from standard MALDI-TOF databases complicates identification. Susceptibility data do not exist, so empiric treatment is the only option for this rare pathogen.


Assuntos
Sarcina , Estômago , Feminino , Humanos , Idoso de 80 Anos ou mais , Clostridium
2.
Microbiome ; 11(1): 68, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004104

RESUMO

BACKGROUND: Many animals and plants acquire their coevolved symbiotic partners shortly post-embryonic development. Thus, during embryogenesis, cellular features must be developed that will promote both symbiont colonization of the appropriate tissues, as well as persistence at those sites. While variation in the degree of maturation occurs in newborn tissues, little is unknown about how this variation influences the establishment and persistence of host-microbe associations. RESULTS: The binary symbiosis model, the squid-vibrio (Euprymna scolopes-Vibrio fischeri) system, offers a way to study how an environmental gram-negative bacterium establishes a beneficial, persistent, extracellular colonization of an animal host. Here, we show that bacterial symbionts occupy six different colonization sites in the light-emitting organ of the host that have both distinct morphologies and responses to antibiotic treatment. Vibrio fischeri was most resilient to antibiotic disturbance when contained within the smallest and least mature colonization sites. We show that this variability in crypt development at the time of hatching allows the immature sites to act as a symbiont reservoir that has the potential to reseed the more mature sites in the host organ when they have been cleared by antibiotic treatment. This strategy may produce an ecologically significant resiliency to the association. CONCLUSIONS: The data presented here provide evidence that the evolution of the squid-vibrio association has been selected for a nascent organ with a range of host tissue maturity at the onset of symbiosis. The resulting variation in physical and chemical environments results in a spectrum of host-symbiont interactions, notably, variation in susceptibility to environmental disturbance. This "insurance policy" provides resiliency to the symbiosis during the critical period of its early development. While differences in tissue maturity at birth have been documented in other animals, such as along the infant gut tract of mammals, the impact of this variation on host-microbiome interactions has not been studied. Because a wide variety of symbiosis characters are highly conserved over animal evolution, studies of the squid-vibrio association have the promise of providing insights into basic strategies that ensure successful bacterial passage between hosts in horizontally transmitted symbioses. Video Abstract.


Assuntos
Aliivibrio fischeri , Vibrio , Animais , Aliivibrio fischeri/genética , Simbiose/fisiologia , Decapodiformes/microbiologia , Decapodiformes/fisiologia , Desenvolvimento Embrionário , Mamíferos
3.
Leuk Lymphoma ; 64(5): 972-980, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36960680

RESUMO

Myeloid sarcoma (MS) is currently considered equivalent to de novo acute myeloid leukemia (AML); however, the relationship between these entities is poorly understood. This retrospective multi-institutional cohort study compared 43 MS with NPM1 mutation to 106 AML with NPM1 mutation. Compared to AML, MS had more frequent cytogenetic abnormalities including complex karyotype (p = .009 and p = .007, respectively) and was enriched in mutations of genes involved in histone modification, including ASXL1 (p = .007 and p = .008, respectively). AML harbored a higher average number of gene mutations (p = .002) including more frequent PTPN11 mutations (p < .001) and mutations of DNA-methylating genes including DNMT3A and IDH1 (both p < .001). MS had significantly shorter overall survival (OS) than AML (median OS: 44.9 vs. 93.2 months, respectively, p = .037). MS with NPM1 mutation has a unique genetic landscape, and poorer OS, compared to AML with NPM1 mutation.


First study comparing genetic profiles of MS and AML with a common disease-defining lesion.NPM1Mut MS may be genetically distinct from NPM1Mut AML.NPM1Mut MS may have inferior overall survival compared to NPM1Mut AML.


Assuntos
Leucemia Mieloide Aguda , Sarcoma Mieloide , Humanos , Medula Óssea/patologia , Proteínas Nucleares/genética , Nucleofosmina , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/genética , Sarcoma Mieloide/patologia , Estudos Retrospectivos , Estudos de Coortes , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico
5.
PLoS Biol ; 18(11): e3000934, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33141816

RESUMO

The regulatory noncoding small RNAs (sRNAs) of bacteria are key elements influencing gene expression; however, there has been little evidence that beneficial bacteria use these molecules to communicate with their animal hosts. We report here that the bacterial sRNA SsrA plays an essential role in the light-organ symbiosis between Vibrio fischeri and the squid Euprymna scolopes. The symbionts load SsrA into outer membrane vesicles, which are transported specifically into the epithelial cells surrounding the symbiont population in the light organ. Although an SsrA-deletion mutant (ΔssrA) colonized the host to a normal level after 24 h, it produced only 2/10 the luminescence per bacterium, and its persistence began to decline by 48 h. The host's response to colonization by the ΔssrA strain was also abnormal: the epithelial cells underwent premature swelling, and host robustness was reduced. Most notably, when colonized by the ΔssrA strain, the light organ differentially up-regulated 10 genes, including several encoding heightened immune-function or antimicrobial activities. This study reveals the potential for a bacterial symbiont's sRNAs not only to control its own activities but also to trigger critical responses promoting homeostasis in its host. In the absence of this communication, there are dramatic fitness consequences for both partners.


Assuntos
Aliivibrio fischeri/genética , Aliivibrio fischeri/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Animais , Decapodiformes/genética , Decapodiformes/imunologia , Decapodiformes/microbiologia , Genes Bacterianos , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade Inata/genética , Imunidade Inata/fisiologia , Mutação , Simbiose/genética , Simbiose/imunologia , Simbiose/fisiologia
6.
Science ; 314(5797): 268-74, 2006 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-16959974

RESUMO

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of approximately 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.


Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Sequência Consenso , Genes Neoplásicos , Mutação , Substituição de Aminoácidos , Linhagem Celular Tumoral , Biologia Computacional , Bases de Dados de Ácidos Nucleicos , Feminino , Genoma Humano , Humanos , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
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