Publications by authors named "Malavika Ramesh"

8 Publications

  • Page 1 of 1

Intracellular localization of the mycobacterial stressosome complex.

Sci Rep 2021 May 12;11(1):10060. Epub 2021 May 12.

Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Box 596, 751 24, Uppsala, Sweden.

Microorganisms survive stresses by alternating the expression of genes suitable for surviving the immediate and present danger and eventually adapt to new conditions. Many bacteria have evolved a multiprotein "molecular machinery" designated the "Stressosome" that integrates different stress signals and activates alternative sigma factors for appropriate downstream responses. We and others have identified orthologs of some of the Bacillus subtilis stressosome components, RsbR, RsbS, RsbT and RsbUVW in several mycobacteria and we have previously reported mutual interactions among the stressosome components RsbR, RsbS, RsbT and RsbUVW from Mycobacterium marinum. Here we provide evidence that "STAS" domains of both RsbR and RsbS are important for establishing the interaction and thus critical for stressosome assembly. Fluorescence microscopy further suggested co-localization of RsbR and RsbS in multiprotein complexes visible as co-localized fluorescent foci distributed at scattered locations in the M. marinum cytoplasm; the number, intensity and distribution of such foci changed in cells under stressed conditions. Finally, we provide bioinformatics data that 17 (of 244) mycobacteria, which lack the RsbRST genes, carry homologs of Bacillus cereus genes rsbK and rsbM indicating the existence of alternative σ activation pathways among mycobacteria.
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http://dx.doi.org/10.1038/s41598-021-89069-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115616PMC
May 2021

Author Correction: Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2020 Mar 18;10(1):5246. Epub 2020 Mar 18.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-61218-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078255PMC
March 2020

Insight into the biology of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members.

Sci Rep 2019 12 17;9(1):19259. Epub 2019 Dec 17.

Department of Cell and Molecular Biology, Box 596, BMC, Uppsala University, SE 751 24, Uppsala, Sweden.

Nontuberculous mycobacteria, NTM, are of growing concern and among these members of the Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clades can cause infections in humans and they are resistant to first-line anti-tuberculosis drugs. They can be isolated from different ecological niches such as soil, tap water and ground water. Mycobacteria, such as Mmuc and Mneo, are classified as rapid growing mycobacteria, RGM, while the most familiar, Mycobacterium tuberculosis, belongs to the slow growing mycobacteria, SGM. Modern "omics" approaches have provided new insights into our understanding of the biology and evolution of this group of bacteria. Here we present comparative genomics data for seventeen NTM of which sixteen belong to the Mmuc- and Mneo-clades. Focusing on virulence genes, including genes encoding sigma/anti-sigma factors, serine threonine protein kinases (STPK), type VII (ESX genes) secretion systems and mammalian cell entry (Mce) factors we provide insight into their presence as well as phylogenetic relationship in the case of the sigma/anti-sigma factors and STPKs. Our data further suggest that these NTM lack ESX-5 and Mce2 genes, which are known to affect virulence. In this context, Mmuc- and Mneo-clade members lack several of the genes in the glycopeptidolipid (GLP) locus, which have roles in colony morphotype appearance and virulence. For the M. mucogenicum type strain, Mmuc, we provide RNASeq data focusing on mRNA levels for sigma factors, STPK, ESX proteins and Mce proteins. These data are discussed and compared to in particular the SGM and fish pathogen Mycobacterium marinum. Finally, we provide insight into as to why members of the Mmuc- and Mneo-clades show resistance to rifampin and isoniazid, and why Mmuc forms a rough colony morphotype.
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http://dx.doi.org/10.1038/s41598-019-55464-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917791PMC
December 2019

Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing.

Sci Rep 2018 08 13;8(1):12040. Epub 2018 Aug 13.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24, Uppsala, Sweden.

Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the "M"- and the "Aronson"-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.
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http://dx.doi.org/10.1038/s41598-018-30152-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089878PMC
August 2018

The Mycobacterium phlei Genome: Expectations and Surprises.

Genome Biol Evol 2016 Apr 8;8(4):975-85. Epub 2016 Apr 8.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, Uppsala, Sweden

Mycobacterium phlei, a nontuberculosis mycobacterial species, was first described in 1898-1899. We present the complete genome sequence for theM. phlei CCUG21000(T)type strain and the draft genomes for four additional strains. The genome size for all five is 5.3 Mb with 69.4% Guanine-Cytosine content. This is ≈0.35 Mbp smaller than the previously reported M. phlei RIVM draft genome. The size difference is attributed partly to large bacteriophage sequence fragments in theM. phlei RIVM genome. Comparative analysis revealed the following: 1) A CRISPR system similar to Type 1E (cas3) in M. phlei RIVM; 2) genes involved in polyamine metabolism and transport (potAD,potF) that are absent in other mycobacteria, and 3) strain-specific variations in the number of σ-factor genes. Moreover,M. phlei has as many as 82 mce(mammalian cell entry) homologs and many of the horizontally acquired genes in M. phlei are present in other environmental bacteria including mycobacteria that share similar habitat. Phylogenetic analysis based on 693 Mycobacterium core genes present in all complete mycobacterial genomes suggested that its closest neighbor is Mycobacterium smegmatis JS623 and Mycobacterium rhodesiae NBB3, while it is more distant toM. smegmatis mc2 155.
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http://dx.doi.org/10.1093/gbe/evw049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860684PMC
April 2016

Comparative Sigma Factor-mRNA Levels in Mycobacterium marinum under Stress Conditions and during Host Infection.

PLoS One 2015 7;10(10):e0139823. Epub 2015 Oct 7.

Department of Cell and Molecular Biology, Uppsala University Biomedical Centre, Uppsala, Sweden.

We have used RNASeq and qRT-PCR to study mRNA levels for all σ-factors in different Mycobacterium marinum strains under various growth and stress conditions. We also studied their levels in M. marinum from infected fish and mosquito larvae. The annotated σ-factors were expressed and transcripts varied in relation to growth and stress conditions. Some were highly abundant such as sigA, sigB, sigC, sigD, sigE and sigH while others were not. The σ-factor mRNA profiles were similar after heat stress, during infection of fish and mosquito larvae. The similarity also applies to some of the known heat shock genes such as the α-crystallin gene. Therefore, it seems probable that the physiological state of M. marinum is similar when exposed to these different conditions. Moreover, the mosquito larvae data suggest that this is the state that the fish encounter when infected, at least with respect to σ-factor mRNA levels. Comparative genomic analysis of σ-factor gene localizations in three M. marinum strains and Mycobacterium tuberculosis H37Rv revealed chromosomal rearrangements that changed the localization of especially sigA, sigB, sigD, sigE, sigF and sigJ after the divergence of these two species. This may explain the variation in species-specific expression upon exposure to different growth conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139823PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596819PMC
June 2016

Characterization of Three Mycobacterium spp. with Potential Use in Bioremediation by Genome Sequencing and Comparative Genomics.

Genome Biol Evol 2015 Jun 16;7(7):1871-86. Epub 2015 Jun 16.

Department of Cell and Molecular Biology, Uppsala University, Sweden

We provide the genome sequences of the type strains of the polychlorophenol-degrading Mycobacterium chlorophenolicum (DSM43826), the degrader of chlorinated aliphatics Mycobacterium chubuense (DSM44219) and Mycobacterium obuense (DSM44075) that has been tested for use in cancer immunotherapy. The genome sizes of M. chlorophenolicum, M. chubuense, and M. obuense are 6.93, 5.95, and 5.58 Mb with GC-contents of 68.4%, 69.2%, and 67.9%, respectively. Comparative genomic analysis revealed that 3,254 genes are common and we predicted approximately 250 genes acquired through horizontal gene transfer from different sources including proteobacteria. The data also showed that the biodegrading Mycobacterium spp. NBB4, also referred to as M. chubuense NBB4, is distantly related to the M. chubuense type strain and should be considered as a separate species, we suggest it to be named Mycobacterium ethylenense NBB4. Among different categories we identified genes with potential roles in: biodegradation of aromatic compounds and copper homeostasis. These are the first nonpathogenic Mycobacterium spp. found harboring genes involved in copper homeostasis. These findings would therefore provide insight into the role of this group of Mycobacterium spp. in bioremediation as well as the evolution of copper homeostasis within the Mycobacterium genus.
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http://dx.doi.org/10.1093/gbe/evv111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524478PMC
June 2015

Asymmetric growth and division in Mycobacterium spp.: compensatory mechanisms for non-medial septa.

Mol Microbiol 2013 Apr 6;88(1):64-76. Epub 2013 Mar 6.

Department of Cell and Molecular Biology, Uppsala University Biomedical Center, Box 596, 751 24 Uppsala, Sweden.

Mycobacterium spp., rod-shaped cells belonging to the phylum Actinomycetes, lack the Min- and Noc/Slm systems responsible for preventing the placement of division sites at the poles or over the nucleoids to ensure septal assembly at mid-cell. We show that the position for establishment of the FtsZ-ring in exponentially growing Mycobacterium marinum and Mycobacterium smegmatis cells is nearly random, and that the cells often divide non-medially, producing two unequal but viable daughters. Septal sites and cellular growth disclosed by staining with the membrane-specific dye FM4-64 and fluorescent antibiotic vancomycin (FL-Vanco), respectively, showed that many division sites were off-centre, often over the nucleoids, and that apical cell growth was frequently unequal at the two poles. DNA transfer through the division septum was detected, and translocation activity was supported by the presence of a putative mycobacterial DNA translocase (MSMEG2690) at the majority of the division sites. Time-lapse imaging of single live cells through several generations confirmed both acentric division site placement and unequal polar growth in mycobacteria. Our evidence suggests that post-septal DNA transport and unequal polar growth may compensate for the non-medial division site placement in Mycobacterium spp.
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http://dx.doi.org/10.1111/mmi.12169DOI Listing
April 2013
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