Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway

Souza, Gustavo; Leversen, Nils Anders; Målen, Hiwa; Wiker, Harald G.

doi:10.1016/j.jprot.2011.08.016

Cited by 174 publications

(156 citation statements)

References 32 publications

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“…Another important feature of the M. tuberculosis Rv3852 protein is its subcellular localization, since it was detected only in the cell membrane and not in the other subcellular compartments or in the culture supernatant (Fig. 2), as reported earlier in a proteomic survey (35). This localization is compatible with a role for Rv3852 in chromosome segregation during cell division, as proposed by Ghosh et al (21).…”

Section: Discussionsupporting

confidence: 85%

Rv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation

et al. 2017

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A handful of nucleoid-associated proteins (NAPs) regulate the vast majority of genes in a bacterial cell. H-NS, the histone-like nucleoid-structuring protein, is one of these NAPs and protects Escherichia coli from foreign gene expression. Though lacking any sequence similarity with E. coli H-NS, Rv3852 was annotated as the H-NS ortholog in Mycobacterium tuberculosis, as it resembles human histone H1. The role of Rv3852 was thoroughly investigated by immunoblotting, subcellular localization, construction of an unmarked rv3852 deletion in the M. tuberculosis genome, and subsequent analysis of the resulting Δrv3852 strain. We found that Rv3852 was predominantly present in the logarithmic growth phase with a decrease in protein abundance in stationary phase. Furthermore, it was strongly associated with the cell membrane and not detected in the cytosolic fraction, nor was it secreted. The Δrv3852 strain displayed no growth defect or morphological abnormalities. Quantitative measurement of nucleoid localization in the Δrv3852 mutant strain compared to that in the parental H37Rv strain showed no difference in nucleoid position or spread. Infection of macrophages as well as severe combined immunodeficient (SCID) mice demonstrated that loss of Rv3852 had no detected influence on the virulence of M. tuberculosis. We thus conclude that M. tuberculosis Rv3852 is not involved in pathogenesis and is not a typical NAP. The existence of an as yet undiscovered Rv3852 ortholog cannot be excluded, although this role is likely played by the well-characterized Lsr2 protein.IMPORTANCE Mycobacterium tuberculosis is the causative agent of the lung infection tuberculosis, claiming more than 1.5 million lives each year. To understand the mechanisms of latent infection, where M. tuberculosis can stay dormant inside the human host, we require deeper knowledge of the basic biology and of the regulatory networks. In our work, we show that Rv3852, previously annotated as H-NS, is not a typical nucleoid-associated protein (NAP) as expected from its initial annotation. Rv3852 from M. tuberculosis has neither influence on nucleoid shape or compaction nor a role in virulence. Our findings reduce the repertoire of identified nucleoid-associated proteins in M. tuberculosis to four transcription regulators and underline the importance of genetic studies to assign a function to bacterial genes. KEYWORDS tuberculosis, Mycobacterium tuberculosis, H-NS, NAP, global regulation, rv3852T he chromosome must be heavily compacted to fit into a bacterial cell about 1,000 times smaller than the length of its DNA. Similarly to eukaryotes, where DNA is wrapped around histones for condensation, prokaryotes possess nucleoid-associated proteins (NAPs), which influence DNA topology. Typically, NAPs interact with the chromosome at several hundred binding sites in a sequence-specific or non-sequencespecific manner (1). As a result, NAPs can bridge, loop, and bend DNA (2), thus

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Section: Discussionsupporting

confidence: 85%

Rv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation

et al. 2017

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“…A subsequent literature search revealed that almost all further selected IVE-TB proteins (14 of the 16) have been identified previously in M. tuberculosis proteomic studies, confirming the protein expression of the M. tuberculosis genes identified in our study (44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) (Table III). Indeed, we observed that M. tuberculosis- FIGURE 3.…”

Section: Immunogenicity Of Newly Identified Ive-tb Agssupporting

confidence: 87%

An Unbiased Genome-Wide Mycobacterium tuberculosis Gene Expression Approach To Discover Antigens Targeted by Human T Cells Expressed during Pulmonary Infection

Commandeur

Meijgaarden

Prins

et al. 2013

The Journal of Immunology

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Mycobacterium tuberculosis is responsible for almost 2 million deaths annually. Mycobacterium bovis bacillus Calmette-Guérin, the only vaccine available against tuberculosis (TB), induces highly variable protection against TB, and better TB vaccines are urgently needed. A prerequisite for candidate vaccine Ags is that they are immunogenic and expressed by M. tuberculosis during infection of the primary target organ, that is, the lungs of susceptible individuals. In search of new TB vaccine candidate Ags, we have used a genome-wide, unbiased Ag discovery approach to investigate the in vivo expression of 2170 M. tuberculosis genes during M. tuberculosis infection in the lungs of mice. Four genetically related but distinct mouse strains were studied, representing a spectrum of TB susceptibility controlled by the supersusceptibility to TB 1 locus. We used stringent selection approaches to select in vivo–expressed M. tuberculosis (IVE-TB) genes and analyzed their expression patterns in distinct disease phenotypes such as necrosis and granuloma formation. To study the vaccine potential of these proteins, we analyzed their immunogenicity. Several M. tuberculosis proteins were recognized by immune cells from tuberculin skin test-positive, ESAT6/CFP10-responsive individuals, indicating that these Ags are presented during natural M. tuberculosis infection. Furthermore, TB patients also showed responses toward IVE-TB Ags, albeit lower than tuberculin skin test-positive, ESAT6/CFP10-responsive individuals. Finally, IVE-TB Ags induced strong IFN-γ+/TNF-α+ CD8+ and TNF-α+/IL-2+ CD154+/CD4+ T cell responses in PBMC from long-term latently M. tuberculosis–infected individuals. In conclusion, these IVE-TB Ags are expressed during pulmonary infection in vivo, are immunogenic, induce strong T cell responses in long-term latently M. tuberculosis–infected individuals, and may therefore represent attractive Ags for new TB vaccines.

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“…Indeed, in both Grampositive and -negative bacteria, this particular residue is often substituted for leucine, an amino acid with an even longer side chain than valine. The second SNP in isolate HN878-27 is a T730C transition that results in the substitution of glutamic acid for glycine (E244G) in Rv1215c, a gene which encodes a hypothetical protein found in the membrane fraction of M. tuberculosis (41,42). As the function of Rv1215c is unknown at present, it is difficult to assess whether a mutation in this protein could have an effect on virulence.…”

Section: Resultsmentioning

confidence: 99%

Origins of a 350-Kilobase Genomic Duplication in Mycobacterium tuberculosis and Its Impact on Virulence

et al. 2014

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bIn the present study, we have investigated the evolution and impact on virulence of a 350-kb genomic duplication present in the most recently evolved members of the Mycobacterium tuberculosis East Asian lineage. In a mouse model of infection, comparing HN878 subclones HN878-27 (no duplication) and HN878-45 (with the 350-kb duplication) revealed that the latter is impaired for in vivo growth during the initial 3 weeks of infection. Furthermore, the median survival time of mice infected with isolate HN878-45 is significantly longer (77 days) than that of mice infected with HN878-27. Whole-genome sequencing of both isolates failed to reveal any mutational events other than the duplication that could account for such a substantial difference in virulence. Although we and others had previously speculated that the 350-kb duplication arose in response to some form of hostapplied selective pressure ( , here we show that this large chromosomal amplification event is very rapidly selected within standard in vitro broth cultures in a range of isolates. Indeed, subclones harboring the duplication were detectable after just five rounds of in vitro passage. In contrast, the duplication appears to be highly unstable in vivo and is negatively selected during the later stages of infection in mice. We believe that the rapid in vitro evolution of M. tuberculosis is an underappreciated aspect of its biology that is often ignored, despite the fact that it has the potential to confound the data and conclusions arising from comparative studies of isolates at both the genotypic and phenotypic levels.

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Bacterial proteins with cleaved or uncleaved signal peptides of the general secretory pathway

Cited by 174 publications

References 32 publications

Rv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation

Rv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation

An Unbiased Genome-Wide Mycobacterium tuberculosis Gene Expression Approach To Discover Antigens Targeted by Human T Cells Expressed during Pulmonary Infection

Origins of a 350-Kilobase Genomic Duplication in Mycobacterium tuberculosis and Its Impact on Virulence

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