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1.
Emerg Infect Dis ; 18(3): 449-57, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22377449

RESUMO

An emergent clone of Haemophilus influenzae biogroup aegyptius (Hae) is responsible for outbreaks of Brazilian purpuric fever (BPF). First recorded in Brazil in 1984, the so-called BPF clone of Hae caused a fulminant disease that started with conjunctivitis but developed into septicemic shock; mortality rates were as high as 70%. To identify virulence determinants, we conducted a pan-genomic analysis. Sequencing of the genomes of the BPF clone strain F3031 and a noninvasive conjunctivitis strain, F3047, and comparison of these sequences with 5 other complete H. influenzae genomes showed that >77% of the F3031 genome is shared among all H. influenzae strains. Delineation of the Hae accessory genome enabled characterization of 163 predicted protein-coding genes; identified differences in established autotransporter adhesins; and revealed a suite of novel adhesins unique to Hae, including novel trimeric autotransporter adhesins and 4 new fimbrial operons. These novel adhesins might play a critical role in host-pathogen interactions.


Assuntos
Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Haemophilus influenzae/patogenicidade , Adesinas Bacterianas/genética , Ordem dos Genes , Genoma Bacteriano , Haemophilus influenzae/classificação , Interações Hospedeiro-Patógeno , Humanos , Anotação de Sequência Molecular , Dados de Sequência Molecular , Óperon , Filogenia , Homologia de Sequência , Virulência , Fatores de Virulência/genética
2.
Proc Natl Acad Sci U S A ; 109(9): 3416-21, 2012 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-22331916

RESUMO

Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections.


Assuntos
Variação Antigênica/genética , Evolução Molecular , Genoma de Protozoário , Evasão da Resposta Imune/genética , Trypanosoma brucei brucei/imunologia , Trypanosoma congolense/imunologia , Trypanosoma vivax/imunologia , Glicoproteínas Variantes de Superfície de Trypanosoma/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA de Protozoário/genética , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Recombinação Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Trypanosoma brucei brucei/genética , Trypanosoma congolense/genética , Trypanosoma vivax/genética , Glicoproteínas Variantes de Superfície de Trypanosoma/química , Glicoproteínas Variantes de Superfície de Trypanosoma/imunologia
3.
BMC Genomics ; 12: 628, 2011 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-22192698

RESUMO

BACKGROUND: Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored. RESULTS: We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5' and 3' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3' UTR of one gene. This is the first report of 3' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia. CONCLUSION: We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor Upc2 role has a conserved role as a major regulator of the hypoxic response in C. parapsilosis and C. albicans.


Assuntos
Candida/genética , Hipóxia Celular , RNA Fúngico/genética , Transcrição Gênica , Genes Fúngicos
4.
Microbiology (Reading) ; 156(Pt 11): 3255-3269, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20829291

RESUMO

Comparison of the complete genome sequence of Bacteroides fragilis 638R, originally isolated in the USA, was made with two previously sequenced strains isolated in the UK (NCTC 9343) and Japan (YCH46). The presence of 10 loci containing genes associated with polysaccharide (PS) biosynthesis, each including a putative Wzx flippase and Wzy polymerase, was confirmed in all three strains, despite a lack of cross-reactivity between NCTC 9343 and 638R surface PS-specific antibodies by immunolabelling and microscopy. Genomic comparisons revealed an exceptional level of PS biosynthesis locus diversity. Of the 10 divergent PS-associated loci apparent in each strain, none is similar between NCTC 9343 and 638R. YCH46 shares one locus with NCTC 9343, confirmed by mAb labelling, and a second different locus with 638R, making a total of 28 divergent PS biosynthesis loci amongst the three strains. The lack of expression of the phase-variable large capsule (LC) in strain 638R, observed in NCTC 9343, is likely to be due to a point mutation that generates a stop codon within a putative initiating glycosyltransferase, necessary for the expression of the LC in NCTC 9343. Other major sequence differences were observed to arise from different numbers and variety of inserted extra-chromosomal elements, in particular prophages. Extensive horizontal gene transfer has occurred within these strains, despite the presence of a significant number of divergent DNA restriction and modification systems that act to prevent acquisition of foreign DNA. The level of amongst-strain diversity in PS biosynthesis loci is unprecedented.


Assuntos
Cápsulas Bacterianas/genética , Bacteroides fragilis/genética , Variação Genética , Genoma Bacteriano , Cápsulas Bacterianas/biossíntese , Bacteroides fragilis/isolamento & purificação , Hibridização Genômica Comparativa , DNA Bacteriano/genética , Humanos , Dados de Sequência Molecular , Análise de Sequência de DNA
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