Biology subjects

Goswami, C.

Publications and source records attributed to Goswami, C..

4 recordsLinked to original sources

bioRxiv2018

A highly conserved complete accessory Escherichia coli type III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage

Bacterial type III secretion systems (T3SS) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that all 26 ST69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. However, comparison of secreted proteins from ST69 strains under high and low eilA activation failed to identify any ETT2 secreted substrates. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has functional importance in infection, although its exact functional role remains obscure.\n\nImportanceOne of the commonest bacteria causing bloodstream infections in humans is Escherichia coli, which has a significant morbidity and mortality. Better understating of the mechanisms by which this microbe can invade blood could lead to more effective prevention and treatment. One mechanism by which some strains cause disease is by elaboration of a specialized secretion system, the type III secretion system (T3SS), encoded by the locus of enterocyte effacement (LEE). In addition to this well-defined T3SS, a second T3SS has been found in some E. coli strains termed E. coli type III secretion system 2 (ETT2). Most strains carry elements of the ETT2 locus, but with significant mutational attrition rendering it functionless. The significance of our work is that we have discovered that human bloodstream isolates of E. coli of sequence type 69 contain a fully intact ETT2 and associated genes, strongly suggesting its functional importance in human infection.

microbiology↗

bioRxiv2018

TRPV4 interacts with mitochondrial proteins and acts as a mitochondrial structure-function regulator

TRPV4 has been linked with the development of sensory defects, neuropathic pain, neurodegenerative disorders such as Charcot Marie Tooth disease and various muscular dystrophies. In all these cases mitochondrial abnormalities were tagged as cellular hallmarks and such abnormalities have been reported as key factor for the pathophysiological conditions. Mitochondria also have the unique ability to sense and regulate their own temperature. Here, we demonstrate that TRPV4, a thermosensitive ion channels, localizes to a subpopulation of mitochondria in various cell lines, in primary cells and also in sperm cells. Improper expression and/or function of TRPV4 induce several mitochondrial abnormalities such as low oxidative potential, high Ca2+-influx and changes in electron transport chain functions. TRPV4 is also involved in regulation of mitochondrial morphology, smoothness, and fusion-fission events. The C-terminal cytoplasmic region of TRPV4 can localize it to mitochondria and interacts with mitochondrial proteins including Hsp60, Mfn1 and Mfn2. Regulation of mitochondria by TRPV4 may contribute to previously uncharacterized mitochondria-specific functions observed in various cell types. This discovery may help to link TRPV4-mediated channelopathies with mitochondria-mediated diseases.

cell biology↗

bioRxiv2018

A role for tetracycline selection in the evolution of Clostridium difficile PCR-ribotype 078

Farm animals have been identified as reservoirs of Clostridium difficile PCR-ribotype 078 (RT078). Since 2005, the incidence of human clinical cases (frequently severe), with this genotype has increased. We aimed to understand this change, by studying the recent evolutionary history of RT078. Phylogenetic analysis of international genomes (isolates from 2006-2014) revealed several recent clonal expansions. A common ancestor of each expansion had independently acquired different alleles of the tetracycline resistance gene tetM. Consequently, an unusually high proportion of RT078 genomes were tetM positive (76.5%). Additional tetracycline resistance determinants were also identified, some for the first time in C. difficile (efflux pump tet40). Each tetM-clonal expansion lacked geographic structure, indicating rapid international spread. Resistance determinants for C. difficile-infection-triggering antimicrobials including fluoroquinolones and clindamycin were comparatively rare in RT078. Tetracyclines are used intensively in agriculture; this selective pressure, plus rapid spread via the food-chain may explain the increased RT078 prevalence in humans.

microbiology↗

bioRxiv2017

A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)

The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.

genomics↗