scholarly journals Genomic Analysis of an Attenuated Chlamydia abortus Live Vaccine Strain Reveals Defects in Central Metabolism and Surface Proteins

2009 ◽  
Vol 77 (9) ◽  
pp. 4161-4167 ◽  
Author(s):  
L. S. Burall ◽  
A. Rodolakis ◽  
A. Rekiki ◽  
G. S. A. Myers ◽  
P. M. Bavoil
Keyword(s):  
Pyruvate Kinase ◽  
Vaccine Strain ◽  
Genomic Analysis ◽  
Live Vaccine ◽  
Surface Proteins ◽  
Comparative Genomic ◽  
Temperature Sensitive ◽  
Nucleotide Polymorphisms ◽  
Chlamydia Abortus ◽  
Virulence Attenuation

ABSTRACT Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.

scholarly journals Comparative Genomic Analysis of Brucella melitensis Vaccine Strain M5 Provides Insights into Virulence Attenuation

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70852 ◽  
Author(s):  
Hai Jiang ◽  
Pengcheng Du ◽  
Wen Zhang ◽  
Heng Wang ◽  
Hongyan Zhao ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Brucella Melitensis ◽  
Genomic Analysis ◽  
Comparative Genomic Analysis ◽  
Comparative Genomic ◽  
Virulence Attenuation

scholarly journals Attenuation of Mycoplasma hyopneumoniae Strain ES-2 and Comparative Genomic Analysis of ES-2 and Its Attenuated Form ES-2L

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhenya Li ◽  
Yingxin Wang ◽  
Yanyan Zhang ◽  
Xibiao Tang ◽  
Xiangru Wang ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Mycoplasma Hyopneumoniae ◽  
Comparative Genomic ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Virulence Attenuation ◽  
Genomic Analyses ◽  
Single Nucleotide Variations ◽  
Highly Virulent

Mycoplasma hyopneumoniae causes swine respiratory disease worldwide. Due to the difficulty of isolating and cultivating M. hyopneumoniae, very few attenuated strains have been successfully isolated, which hampers the development of attenuated vaccines. In order to produce an attenuated M. hyopneumoniae strain, we used the highly virulent M. hyopneumoniae strain ES-2, which was serially passaged in vitro 200 times to produce the attenuated strain ES-2L, and its virulence was evidenced to be low in an animal experiment. In order to elucidate the mechanisms underlying virulence attenuation, we performed whole-genome sequencing of both strains and conducted comparative genomic analyses of strain ES-2 and its attenuated form ES-2L. Strain ES-2L showed three large fragment deletion regions including a total of 18 deleted genes, compared with strain ES-2. Analysis of single-nucleotide polymorphisms (SNPs) and indels indicated that 22 dels were located in 19 predicted coding sequences. In addition to these indels, 348 single-nucleotide variations (SNVs) were identified between strains ES-2L and ES-2. These SNVs mapped to 99 genes where they appeared to induce amino acid substitutions and translation stops. The deleted genes and SNVs may be associated with decreased virulence of strain ES-2L. Our work provides a foundation for further examining virulence factors of M. hyopneumoniae and for the development of attenuated vaccines.

scholarly journals Deciphering the Molecular Basis for Attenuation of Flavobacterium columnare Strain Fc1723 Used as Modified Live Vaccine against Columnaris Disease

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1370
Author(s):  
Wenlong Cai ◽  
Covadonga R. Arias
Keyword(s):  
Vaccine Strain ◽  
Molecular Basis ◽  
Live Vaccine ◽  
Gliding Motility ◽  
Genome Comparison ◽  
Comparative Genomic ◽  
Flavobacterium Columnare ◽  
Secretion Systems ◽  
Columnaris Disease ◽  
Modified Live Vaccine

Vaccines are widely employed in aquaculture to prevent bacterial infections, but their use by the U.S. catfish industry is very limited. One of the main diseases affecting catfish aquaculture is columnaris disease, caused by the bacterial pathogen Flavobacterium columnare. In 2011, a modified-live vaccine against columnaris disease was developed by selecting mutants that were resistant to rifampin. The previous study has suggested that this vaccine is stable, safe, and effective, but the mechanisms that resulted in attenuation remained uncharacterized. To understand the molecular basis for attenuation, a comparative genomic analysis was conducted to identify specific point mutations. The PacBio RS long-read sequencing platform was used to obtain draft genomes of the mutant attenuated strain (Fc1723) and the parent virulent strain (FcB27). Sequence-based genome comparison identified 16 single nucleotide polymorphisms (SNP) unique to the mutant. Genes that contained mutations were involved in rifampin resistance, gliding motility, DNA transcription, toxin secretion, and extracellular protease synthesis. The results also found that the vaccine strain formed biofilm at a significantly lower rate than the parent strain. These observations suggested that the rifampin-resistant phenotype and the associated attenuation of the vaccine strain result from the altered activity of RNA polymerase (RpoB) and possible disrupted protein secretion systems.

scholarly journals Comparative Study of the Molecular Basis of Pathogenicity of M. bovis Strains in a Mouse Model

2018 ◽  
Vol 20 (1) ◽  
pp. 5 ◽  
Author(s):  
Guangyu Cheng ◽  
Tariq Hussain ◽  
Naveed Sabir ◽  
Jiamin Ni ◽  
Miaoxuan Li ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Virulence Factors ◽  
Genomic Analysis ◽  
Interferon Γ ◽  
Comparative Genomic ◽  
Interleukin 17 ◽  
Nucleotide Polymorphisms ◽  
Serum Samples ◽  
Different Strains

It is widely accepted that different strains of Mycobacterium tuberculosis have variable degrees of pathogenicity and induce different immune responses in infected hosts. Similarly, different strains of Mycobacterium bovis have been identified but there is a lack of information regarding the degree of pathogenicity of these strains and their ability to provoke host immune responses. Therefore, in the current study, we used a mouse model to evaluate various factors involved in the severity of disease progression and the induction of immune responses by two strains of M. bovis isolated from cattle. Mice were infected with both strains of M. bovis at different colony-forming unit (CFU) via inhalation. Gross and histological findings revealed more severe lesions in the lung and spleen of mice infected with M. bovis N strain than those infected with M. bovis C68004 strain. In addition, high levels of interferon-γ (IFN-γ), interleukin-17 (IL-17), and IL-22 production were observed in the serum samples of mice infected with M. bovis N strain. Comparative genomic analysis showed the existence of 750 single nucleotide polymorphisms and 145 small insertions/deletions between the two strains. After matching with the Virulence Factors Database, mutations were found in 29 genes, which relate to 17 virulence factors. Moreover, we found an increased number of virulent factors in M. bovis N strain as compared to M. bovis C68004 strain. Taken together, our data reveal that variation in the level of pathogenicity is due to the mutation in the virulence factors of M. bovis N strain. Therefore, a better understanding of the mechanisms of mutation in the virulence factors will ultimately contribute to the development of new strategies for the control of M. bovis infection.

scholarly journals Genomic analysis on Brazilian strains of Anaplasma marginale

2021 ◽  
Vol 30 (2) ◽  
Author(s):  
Bruno Dall’Agnol ◽  
Anelise Webster ◽  
Ugo Araújo Souza ◽  
Antonela Barbieri ◽  
Fabiana Quoos Mayer ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Anaplasma Marginale ◽  
Surface Proteins ◽  
Reference Sequence ◽  
South American ◽  
Nucleotide Polymorphisms ◽  
Whole Genomes ◽  
History Of ◽  
Vector Borne ◽  
Genome Information

Abstract Anaplasma marginale is a vector-borne pathogen that causes a disease known as anaplasmosis. No sequenced genomes of Brazilian strains are yet available. The aim of this work was to compare whole genomes of Brazilian strains of A. marginale (Palmeira and Jaboticabal) with genomes of strains from other regions (USA and Australia strains). Genome sequencing of Brazilian strains was performed by means of next-generation sequencing. Reads were mapped using the genome of the Florida strain of A. marginale as a reference sequence. Single nucleotide polymorphisms (SNPs) and insertions/deletions (INDELs) were identified. The data showed that two Brazilian strains grouped together in one particular clade, which grouped in a larger American group together with North American strains. Moreover, some important differences in surface proteins between the two Brazilian isolates can be discerned. These results shed light on the evolutionary history of A. marginale and provide the first genome information on South American isolates. Assessing the genome sequences of strains from different regions is essential for increasing knowledge of the pan-genome of this bacteria.

scholarly journals Genomic characteristics of recently recognized Vibrio cholerae El Tor lineages associated with cholera in Bangladesh, 1991-2017

2021 ◽  
Author(s):  
Md Mamun Monir ◽  
Talal Hossain ◽  
Masatomo Morita ◽  
Makoto Ohnishi ◽  
Fatema-tuj Johura ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Genome Wide Association Study ◽  
Sequence Data ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Nucleotide Polymorphisms ◽  
Fitness Advantage ◽  
Genome Phylogeny ◽  
El Tor ◽  
Endemic Cholera

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in depth whole genome study of V. cholerae El Tor clinical strains isolated during endemic cholera in Bangladesh (1991 – 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. choleraeEl Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera 2004-2017. Genome wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of the endemic cholera in Bangladesh, with implications for global cholera epidemiology.

scholarly journals Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution

2020 ◽  
Author(s):  
Roshan Kumar ◽  
Helianthous Verma ◽  
Nirjara Singhvi ◽  
Utkarsh Sood ◽  
Vipin Gupta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Treatment Strategies ◽  
Genomic Analysis ◽  
Viral Proteins ◽  
Comparative Genomic ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Human Interactome ◽  
Geographical Regions ◽  
The Usa

AbstractThe Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.

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