Genome reduction in prokaryotic obligatory intracellular parasites of humans: a comparative analysis

Sakharkar, Kishore R.; Dhar, Pawan K.; Chow, Vincent T. K.

doi:10.1099/ijs.0.63090-0

Cited by 66 publications

(49 citation statements)

References 18 publications

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“…Consistent with other obligate intracellular bacteria (3,23,55,84), and as proposed by Seshadri et al (63), our results suggest that the C. burnetii genome is undergoing reductive evolution. Accordingly, we found very few polymorphisms resulting from DNA insertion.…”

Section: Discussionsupporting

confidence: 80%

“…Analysis of coding ORFs indicates that, although C. burnetii shares similarities in lifestyle and parasitic strategies to other obligate intracellular bacteria, it generally differs considerably with respect to genome size, metabolic and transporter capabilities, the presence of mobile genetic elements, and the extent of genome reduction (23,55,57,63,84). To further define the genetic diversity of C. burnetii, gDNA of 24 isolates of diverse geographical and environmental origins were hybridized to a custom Affymetrix microarray chip (RMLchip_a) containing probe sets corresponding to all ORFs of the NMI isolate.…”

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confidence: 99%

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Genetic Diversity of the Q Fever Agent,Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons

Beare¹,

Samuel

Howe³

et al. 2006

J Bacteriol

125

132

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Coxiella burnetii, a gram-negative obligate intracellular bacterium, causes human Q fever and is considered a potential agent of bioterrorism. Distinct genomic groups of C. burnetii are revealed by restriction fragmentlength polymorphisms (RFLP). Here we comprehensively define the genetic diversity of C. burnetii by hybridizing the genomes of 20 RFLP-grouped and four ungrouped isolates from disparate sources to a high-density custom Affymetrix GeneChip containing all open reading frames (ORFs) of the Nine Mile phase I (NMI) reference isolate. We confirmed the relatedness of RFLP-grouped isolates and showed that two ungrouped isolates represent distinct genomic groups. Isolates contained up to 20 genomic polymorphisms consisting of 1 to 18 ORFs each. These were mostly complete ORF deletions, although partial deletions, point mutations, and insertions were also identified. A total of 139 chromosomal and plasmid ORFs were polymorphic among all C. burnetii isolates, representing ca. 7% of the NMI coding capacity. Approximately 67% of all deleted ORFs were hypothetical, while 9% were annotated in NMI as nonfunctional (e.g., frameshifted). The remaining deleted ORFs were associated with diverse cellular functions. The only deletions associated with isogenic NMI variants of attenuated virulence were previously described large deletions containing genes involved in lipopolysaccharide (LPS) biosynthesis, suggesting that these polymorphisms alone are responsible for the lower virulence of these variants. Interestingly, a variant of the Australia QD isolate producing truncated LPS had no detectable deletions, indicating LPS truncation can occur via small genetic changes. Our results provide new insight into the genetic diversity and virulence potential of Coxiella species.

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Genetic Diversity of the Q Fever Agent,Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons

Beare¹,

Samuel

Howe³

et al. 2006

J Bacteriol

125

132

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“…Besides the lack of biosynthesis, several nutrient transporters that are not found in any other crenarchaeote are present in T. pendens. A lack of biosynthetic ability and an increase in nutrient transport ability are features commonly found in obligate parasites (49). However, T. pendens lacks other features of obligate intracellular parasites, such as a reduced genome size (40,62), a loss of signal transduction and DNA repair proteins (36), an increased percentage of A ⅐ T base pairs (35,62), and a decreased number of fusion proteins (K. Mavromatis and N. C. Kyrpides, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Genome Sequence of Thermofilum pendens Reveals an Exceptional Loss of Biosynthetic Pathways without Genome Reduction

Anderson

Rodriguez²,

Susanti

et al. 2008

J Bacteriol

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We report the complete genome of Thermofilum pendens, a deeply branching, hyperthermophilic member of the order Thermoproteales in the archaeal kingdom Crenarchaeota. T. pendens is a sulfur-dependent, anaerobic heterotroph isolated from a solfatara in Iceland. It is an extracellular commensal, requiring an extract of Thermoproteus tenax for growth, and the genome sequence reveals that biosynthetic pathways for purines, most amino acids, and most cofactors are absent. In fact, T. pendens has fewer biosynthetic enzymes than obligate intracellular parasites, although it does not display other features that are common among obligate parasites and thus does not appear to be in the process of becoming a parasite. It appears that T. pendens has adapted to life in an environment rich in nutrients. T. pendens was known previously to utilize peptides as an energy source, but the genome revealed a substantial ability to grow on carbohydrates. T. pendens is the first crenarchaeote and only the second archaeon found to have a transporter of the phosphotransferase system. In addition to fermentation, T. pendens may obtain energy from sulfur reduction with hydrogen and formate as electron donors. It may also be capable of sulfur-independent growth on formate with formate hydrogen lyase. Additional novel features are the presence of a monomethylamine:corrinoid methyltransferase, the first time that this enzyme has been found outside the Methanosarcinales, and the presence of a presenilin-related protein.The predicted highly expressed proteins do not include proteins encoded by housekeeping genes and instead include ABC transporters for carbohydrates and peptides and clustered regularly interspaced short palindromic repeat-associated proteins.Crenarchaeota is one of the two major divisions of the Archaea, and it is the least well represented taxon in terms of genome sequences. Only seven crenarchaeal genomes have been sequenced and published so far, and three of these are genomes of members of the genus Sulfolobus. For the order Thermoproteales, the complete sequence of only one organism, Pyrobaculum aerophilum, has been determined and published so far, although several more species of Pyrobaculum, Caldivirga maquilingensis, and Thermoproteus tenax have been or are currently being sequenced (29). Thermofilum pendens represents a deep branch in the order Thermoproteales, and this organism grows only in rich medium with a fraction of the polar lipids of T. tenax (64), a property that has not been seen before in archaea. Therefore, it was an attractive sequencing target. We report here the genome sequence of T. pendens and analysis of the type strain, T. pendens Hrk5.T. pendens is an anaerobic, sulfur-dependent hyperthermophile isolated from a solfatara in Iceland. It forms long thin filaments and may have an unusual mode of reproduction in which spherical bulges form at one end of the cell. It requires complex media and a lipid extract from the related organism T. tenax for growth (64). The unknown lipid may be a cellular componen...

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“…Sakharkar et al [12] reported that throughout evolution, genes that once played major roles are eventually discarded because they are no longer under selective pressure. Genome stability is therefore achieved by the loss of selected groups of proteins involved in genome dynamics and gene mobility [12]. Gene degradation targets overlapping subsets of potentially dispensable genes while adapting to the selective pressures of different niches [13].…”

Section: Genomics In Understanding Host-specifi C Adaptations and Genmentioning

confidence: 99%

“…In efforts to characterize the evolutionary forces underlying genome reduction and to understand the dynamics of microbial genomes, a critical issue concerns the size, content and processes of deletions [12]. The reduction in genome size of obligatory intracellular parasites results in genome stability via loss of selected groups of proteins, e.g.…”

Section: Genomics In Understanding Host-specifi C Adaptations and Genmentioning

confidence: 99%

Microbial genomics: rhetoric or reality?

Sakharkar

Chow

2008

Indian J Microbiol

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The availability of complete genome sequences of many bacterial species is facilitating numerous computational approaches for understanding bacterial genomes. One of the major incentives behind the genome sequencing of many pathogenic bacteria is the desire to better understand their diversity and to develop new approaches for controlling human diseases caused by these microorganisms. This task has become even more urgent with the rapid evolution of antibiotic resistance among many bacterial pathogens. Novel drug targets are required in order to design new antimicrobials against antibiotic-resistant pathogens. The complete genome sequences of an ever increasing number of pathogenic microbes constitute an invaluable resource and provide lead information on potential drug targets. This review focuses on in silico analyses of microbial genomes, their host-specifi c adaptations, with specifi c reference to genome architecture, design, evolution, and trends in computational identifi cation of microbial drug targets. These trends underscore the utility of genomic data for systematic in silico drug target identifi cation in the post-genomic era.

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Genome reduction in prokaryotic obligatory intracellular parasites of humans: a comparative analysis

Cited by 66 publications

References 18 publications

Genetic Diversity of the Q Fever Agent,Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons

Genetic Diversity of the Q Fever Agent,Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons

Genome Sequence of Thermofilum pendens Reveals an Exceptional Loss of Biosynthetic Pathways without Genome Reduction

Microbial genomics: rhetoric or reality?

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