Genome Reduction Promotes Increase in Protein Functional Complexity in Bacteria

Kelkar, Yogeshwar D.; Ochman, Howard

doi:10.1534/genetics.112.145656

Cited by 41 publications

(37 citation statements)

References 32 publications

(44 reference statements)

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“…Due to the complex and rich intercellular host environments encountered by the strictly host-associated and highly invasive pathogenic treponemes during infection, these additional domains may have been rendered functionally redundant or unnecessary, resulting in loss during the course of treponemal evolution. Obligate pathogenic bacteria, such as T. pallidum, frequently undergo genomic reduction (59,60) and compensate for this genetic loss by encoding "multitasking" proteins, thereby increasing protein functional complexity compared to orthologous proteins from bacteria that are not strictly host-dependent (59,61). The gain of an adhesion/protease-mediated function in the T. pallidum Tp0750 and pallilysin orthologs is consistent with increased protein functional complexity resulting from evolutionary genomic reduction and an obligate pathogenic lifestyle.…”

Section: Discussionmentioning

confidence: 82%

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

et al. 2015

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The spirochete Treponema pallidum subsp. pallidum is the causative agent of syphilis, a chronic, sexually transmitted infection characterized by multiple symptomatic and asymptomatic stages. Although several other species in the genus are able to cause or contribute to disease, T. pallidum differs in that it is able to rapidly disseminate via the bloodstream to tissue sites distant from the site of initial infection. It is also the only Treponema species able to cross both the blood-brain and placental barriers. Previously, the T. pallidum proteins, Tp0750 and Tp0751 (also called pallilysin), were shown to degrade host proteins central to blood coagulation and basement membrane integrity, suggesting a role for these proteins in T. pallidum dissemination and tissue invasion. In the present study, we characterized Tp0750 and Tp0751 sequence variation in a diversity of pathogenic and nonpathogenic treponemes. We also determined the proteolytic potential of the orthologs from the less invasive species Treponema denticola and Treponema phagedenis. These analyses showed high levels of sequence similarity among Tp0750 orthologs from pathogenic species. For pallilysin, lower levels of sequence conservation were observed between this protein and orthologs from other treponemes, except for the ortholog from the highly invasive rabbit venereal syphilis-causing Treponema paraluiscuniculi. In vitro host component binding and degradation assays demonstrated that pallilysin and Tp0750 orthologs from the less invasive treponemes tested were not capable of binding or degrading host proteins. The results show that pallilysin and Tp0750 host protein binding and degradative capability is positively correlated with treponemal invasiveness.

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Section: Discussionmentioning

confidence: 82%

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

et al. 2015

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“…3). Proteins retained by these small genomes may have a widened functional complexity compared to orthologs in larger genomes, 79 and small mutualist genomes tend to lose redundant pathways, or duplicate components that can perform the same function to a certain extent. 80 Even so, it seems clear that their extensive genome reduction leads to metabolic simplification.…”

Section: Genome Size and Structurementioning

confidence: 99%

Endosymbiont evolution: predictions from theory and surprises from genomes

Wernegreen

2015

Annals of the New York Academy of Sciences

109

126

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Genome data has created new opportunities to untangle evolutionary processes shaping microbial variation. Among bacteria, long-term mutualists of insects represent the smallest and (typically) most AT-rich genomes. Evolutionary theory provides a context to predict how an endosymbiotic lifestyle may alter fundamental evolutionary processes - mutation, selection, genetic drift, and recombination - and thus contribute to extreme genomic outcomes. These predictions can then be explored by comparing evolutionary rates, genome size and stability, and base compositional biases across endosymbiotic and free-living bacteria. Recent surprises from such comparisons include genome reduction among uncultured, free-living species. Some studies suggest that selection generally drives this streamlining, while drift drives genome reduction in endosymbionts; however, this remains an hypothesis requiring additional data. Unexpected evidence of selection acting on endosymbiont GC content hints that even weak selection may be effective in some long-term mutualists. Moving forward, intraspecific analysis offers a promising approach to distinguish underlying mechanisms, by testing the null hypothesis of neutrality and by quantifying mutational spectra. Such analyses may clarify whether endosymbionts and free-living bacteria occupy distinct evolutionary trajectories or alternatively, represent varied outcomes of similar underlying forces.

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“…The genome of P. aeruginosa strain PAO1 encodes a predicted 5569 open reading frames (ORFs) and remains one of the largest sequenced bacterial genomes on a single chromosome with 36% of hypothetical proteins [5]. While most bacterial pathogens adopt a strategy of genome reduction [6, 7], the plasticity of the P. aeruginosa genome that allows incorporation of acquired DNA, has enabled the bacterium to thrive in a diverse range of habitats [8]. The genome also aids in clinical setting by encoding numerous virulence factors to establish and maintain an infection, as well as for different antibiotic resistance mechanisms [9, 10].…”

Section: Introductionmentioning

confidence: 99%

LTQ-XL mass spectrometry proteome analysis expands the Pseudomonas aeruginosa AmpR regulon to include cyclic di-GMP phosphodiesterases and phosphoproteins, and identifies novel open reading frames

Kumari

Murugapiran

Balasubramanian

et al. 2014

Journal of Proteomics

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Pseudomonas aeruginosa is well known for its antibiotic resistance and intricate regulatory network, contributing to its success as an opportunistic pathogen. This study is an extension of our transcriptomic analyses (microarray and RNA-Seq) to understand the global changes in PAO1 upon deleting a gene encoding a transcriptional regulator AmpR, in the presence and absence of β-lactam antibiotic. This study was performed under identical conditions to explore the proteome profile of the ampR deletion mutant (PAOΔampR) using GeLC-MS analysis. The proteomic data identified ~53% of total PAO1 proteins and expanded the master regulatory role of AmpR in determining antibiotic resistance and multiple virulence phenotypes in P. aeruginosa. AmpR proteome analysis identified 853 AmpR-dependent proteins, which include 102 transcriptional regulators and 21 two-component system proteins. AmpR also regulates cyclic di-GMP phosphodiesterases (PA4367, PA4969, PA4781) possibly affecting major virulence systems. Phosphoproteome analysis also suggests a significant role for AmpR in Ser, Thr and Tyr phosphorylation. These novel mechanisms of gene regulation were previously not associated with AmpR. The proteome analysis also identified many unannotated and misannotated ORFs in the P. aeruginosa genome. Thus, our data sheds light on important virulence regulatory pathways that can potentially be exploited to deal with P. aeruginosa infections.

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Genome Reduction Promotes Increase in Protein Functional Complexity in Bacteria

Cited by 41 publications

References 32 publications

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum

Endosymbiont evolution: predictions from theory and surprises from genomes

LTQ-XL mass spectrometry proteome analysis expands the Pseudomonas aeruginosa AmpR regulon to include cyclic di-GMP phosphodiesterases and phosphoproteins, and identifies novel open reading frames

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