Conjugal rites of mycobacteria

Bhatt, Apoorva; Jacobs, William R.

doi:10.1038/ng0503-3

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…GSEA software (v4.0.3) ( 17 , 18 ) was carried out to explore the mechanisms of SLC2A3 expression on the progression of CRC. HALLMARK gene set was obtained from MSigDB database V7.2.…”

Section: Methodsmentioning

confidence: 99%

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

et al. 2021

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SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

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“…GSEA software (v4.0.3) ( 17 , 18 ) was carried out to explore the mechanisms of SLC2A3 expression on the progression of CRC. HALLMARK gene set was obtained from MSigDB database V7.2.…”

Section: Methodsmentioning

confidence: 99%

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

et al. 2021

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“…Recently, we have described a chromosomally encoded transfer system in Mycobacterium smegmatis, which operates by a previously undescribed mechanism (6,7). M. smegmatis chromosome transfer requires extended contact between two viable bacteria (a donor and a recipient), is unidirectional, and is resistant to DNase I; thus, it meets the working definition of conjugal transfer (12).…”

mentioning

confidence: 99%

“…A comprehensive understanding of the biology of this organism is critical for the identification of novel drug targets, the development of vaccines, and determining how it evades the host immune system; this requires the development of basic molecular techniques to determine the genetic and biochemical basis of pathogenesis and drug resistance (2,3). Our recent efforts have been focused on the characterization of a conjugation system and its application for use in mycobacterial genetics (4)(5)(6)(7).…”

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confidence: 99%

The RD1 virulence locus ofMycobacterium tuberculosisregulates DNA transfer inMycobacterium smegmatis

Flint

Kowalski

Karnati

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

127

133

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Conjugal DNA transfer occurs by an atypical mechanism in Mycobacterium smegmatis. The transfer system is chromosomally encoded and requires recipient recombination functions for both chromosome and plasmid transfer. Cis-acting sequences have been identified that confer mobility on nontransferable plasmids, but these are larger and have different properties to canonical oriT sites found in bacterial plasmids. To identify trans-acting factors required for mediating DNA transfer, a library of transposon insertion mutants was generated in the donor strain, and individual mutants were screened for their effect on transfer. From this screen, a collection of insertion mutants was isolated that increased conjugation frequencies relative to wild type. Remarkably, the mutations map to a 25-kb region of the M. smegmatis chromosome that is syntenous with the RD1 region of Mycobacterium tuberculosis, which is considered to be the primary attenuating deletion in the related vaccine strain Mycobacterium bovis bacillus Calmette-Gué rin. The genes of the RD1 region encode a secretory apparatus responsible for exporting Cfp10-and Esat-6, both potent antigens and virulence factors. In crosses using two M. smegmatis donors, we show that wild-type cells can suppress the elevated transfer phenotype of mutant donors, which is consistent with the secretion of a factor that suppresses conjugation. Most importantly, the RD1 region of M. tuberculosis complements the conjugation phenotype of the RD1 mutants in M. smegmatis. Our results indicate that the M. tuberculosis and M. smegmatis RD1 regions are functionally equivalent and provide a unique perspective on the role of this critical secretion apparatus.

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“…However, for many bacterial pathogens, efficient methods of engineering DNA have still to be developed, hindering the progress towards a molecular understanding of pathogenesis and virulence. Recently, conjugation has been added to the molecular‐genetic arsenal for the study of mycobacteria (Parsons et al ., 1998; Bhatt and Jacobs, 2003; Wang et al ., 2003). Not only do we anticipate that this will be an important genetic tool, but also our initial studies indicate that it occurs by a novel mechanism distinct from the conventional conjugative‐plasmid systems (Zechner et al ., 2000; Grohmann et al ., 2003).…”

Section: Introductionmentioning

confidence: 99%

Plasmid DNA transfer in Mycobacterium smegmatis involves novel DNA rearrangements in the recipient, which can be exploited for molecular genetic studies

Wang

Derbyshire

2004

Molecular Microbiology

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SummaryThe establishment of molecular genetic techniques is essential for development of new treatments for mycobacterial infections. To this end, we recently described a novel DNA transfer process that occurs in the model mycobacterial organism Mycobacterium smegmatis . This transfer system is most like conjugal DNA transfer in that it requires two viable parents, is DNAse resistant and occurs between distinct donor and recipient strains. Cis -acting sequences called bom , which confer transferability, are distinct from the prototypical oriT sites of conjugative plasmids, as they occur at multiple locations in the chromosome and require RecA in the recipient to mediate plasmid recircularization. Here, we show that a plasmid containing two of these bom regions can undergo several fates in the recipient cell, each of which require recipient recombination functions. The products of plasmid transfer that we observed provide further insights toward a model for DNA transfer. Furthermore, we have taken advantage of the recombination events that occur in the recipient to develop simple procedures for capturing, or replacing specific segments of the recipient chromosome. To demonstrate the potential of the system, we describe the capture and deletion of 25 kb of the M. smegmatis chromosome, and targeted-allele exchange of the recipient recB and recD genes. Using these transfer-mediated rearrangements, we demonstrate that homology with the recipient chromosome and RecB, but not RecD, are essential for DNA transfer.

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Conjugal rites of mycobacteria

Cited by 5 publications

References 14 publications

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer

The RD1 virulence locus ofMycobacterium tuberculosisregulates DNA transfer inMycobacterium smegmatis

Plasmid DNA transfer in Mycobacterium smegmatis involves novel DNA rearrangements in the recipient, which can be exploited for molecular genetic studies

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