Biology subjects

Sultana, S.

Publications and source records attributed to Sultana, S..

23 records · Page 2Linked to original sources

bioRxiv2021

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenic Escherichia coli exquisitely resistant to reactive chlorine species

The ability to overcome stressful environments is critical for pathogen survival in the host. One challenge for bacteria is the exposure to reactive chlorine species (RCS), which are generated by innate immune cells as critical part of the oxidative burst. Hypochlorous acid (HOCl) is the most potent antimicrobial RCS and associated with extensive macromolecular damage in the phagocytized pathogen. However, bacteria have evolved defense strategies to alleviate the effects of HOCl-mediated damage. Among these are RCS-sensing transcriptional regulators that control the expression of HOCl-protective genes under non- and HOCl stress. Uropathogenic Escherichia coli (UPEC), the major causative agent of urinary tract infections (UTIs), is particularly exposed to infiltrating neutrophils during pathogenesis, however, their responses to and defenses of HOCl are still completely unexplored. Here, we present evidence that UPEC strains tolerate higher levels of HOCl and are better protected from neutrophil-mediated killing compared to other E. coli. Transcriptomic analysis of HOCl-stressed UPEC revealed the upregulation of an operon consisting of three genes, one of which encodes the transcriptional regulator C3600. We identified C3600 as a HOCl-sensing transcriptional repressor, which, under non-stress conditions, is bound to the operator and represses the expression of its target genes. During HOCl exposure, however, the repressor forms reversible intermolecular disulfide bonds and dissociates from the DNA resulting in the de-repression of the operon. Deletion of one of the target genes renders UPEC significantly more susceptible to HOCl indicating that the HOCl-mediated induction of the regulon plays a major role for UPECs HOCl resistance. IMPORTANCEHow do pathogens deal with antimicrobial oxidants produced by the innate immune system during infection? Uropathogenic Escherichia coli (UPEC), the most common etiological agent of urinary tract infections (UTIs), is particularly exposed to infiltrating neutrophils and, therefore, must counter elevated levels of the antimicrobial oxidant HOCl to establish infection. Our study provides fundamentally new insights into a defense mechanism that enables UPEC to fend off the toxic effects of HOCl stress. Intriguingly, the defense system is predominantly found in UPEC and absent in non-invasive enteropathogenic E. coli. Our data suggest that expression of the target gene c3601 is exclusively responsible for UPECs increased HOCl tolerance in culture and therefore potentially contributes to UPECs survival during phagocytosis. Thus, this novel HOCl stress defense system could potentially serve as an attractive drug target to increase the bodys own capacity to fight UTIs.

microbiology↗

bioRxiv2020

Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase

Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Promoter melting initiates in PIC with MTF1 trapping the -4 to -2 non-template (NT) bases in its NT-groove. Transition to IC is marked by a large-scale movement that aligns the template with RNA at the active site. RNA synthesis scrunches the NT strand into an NT-loop, which interacts with centrally positioned MTF1 C-tail. Steric clashes of the C-tail with RNA:DNA and NT-loop, and dynamic scrunching-unscrunching of DNA explain abortive synthesis and transition into elongation. Capturing the catalytically active IC-state with UTPS poised for incorporation enables modeling toxicity of antiviral nucleosides/nucleotides.

biophysics↗

bioRxiv2019

Bioaccumulation of heavy metals in commercially important fish species from the tropical river estuary suggests higher potential child health risk than adults

The Karnaphuli, a major river of Bangladesh, located off the coast of Chittagong in the Bay of Bengal is largely exposed to the heavy metal pollutants, which may be toxic to humans and aquatic fauna. The estuary is a striking example of a site where human pressure and ecological values collide with each other. In spite of being a major supplier of fish food for local community, there has been no study carried out to date to assess the potential human health risk due to heavy metal contamination in the fish species from this estuary. Therefore, the aim of present study was to assess bioaccumulation status and the potential human health risk evaluation for local consumers. Six commercially important fish species, Apocryptes bato, Pampus chinensis, Hyporhamphus limbatus, Liza parsia, Mugil cephalus, and Tenualosa toil from the Karnaphuli River estuary were collected to analyze heavy metals concentration level. Heavy metals As, Pb, Cd, Cr and Cu were detected from the samples using inductively coupled plasma mass spectrometry (Model: ELAN9000, Perkin-Elmer, Germany). The hierarchy of the measured concentration level of the metals was as follows: Pb (mean: 13.88, range: 3.19 - 6.19) > Cu (mean: 12.10, range: 10.27 - 16.41) > As (mean: 4.89, range: 3.19 - 6.19) > Cr (mean: 3.36, range: 2.46 - 4.17) > Cd (mean: 0.39, range: 0.21 - 0.74). The Fultons condition factor denoted that organisms were particularly in better condition and most of the species were in positive allometric growth. The Bioaccumulation factors (BAFs) observed in the species of the contaminants were organized in the following ranks: Cu (1971.42) > As (1042.93) > Pb (913.66) > Cr (864.99) > Cd (252.03), and among all the specimens, demersal fish, A. bato corresponded to the maximum bio-accumulative organism. Estimated daily intake (EDI), target hazard quotient (THQ) and carcinogenic risk (CR) assessed for human health risk implications suggest that the values are within the acceptable threshold for all sorts of consumers. Hence none of them would experience non-carcinogenic and carcinogenic health effect for the ingestion of the fishes. However, children are shown to be largely susceptible than adults to non-carcinogenic and carcinogenic health effect due to the consumption of fish. Therefore, an appropriate guidlines and robust management measures needed to be taken to restore the estuarine health condition for greater benefit of the quality of fish products for local consumption.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC=\"FIGDIR/small/681478v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@802d07org.highwire.dtl.DTLVardef@10c300eorg.highwire.dtl.DTLVardef@126f608org.highwire.dtl.DTLVardef@e28cf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2019

Impacts of climate change on high priority fruit fly species in Australia

Tephritid fruit flies are among the most destructive horticultural pests and pose risks to Australias multi-billion-dollar horticulture industry. Currently, there are 11 pest fruit fly species of economic concern present in various regions of Australia. Of these, nine are native to this continent (Bactrocera aquilonis, B. bryoniae, B. halfordiae, B. jarvisi, B. kraussi, B. musae, B. neohumeralis, B. tryoni and Zeugodacus cucumis), while B. frauenfeldi and Ceratitis capitata are introduced. To varying degrees these species are costly to Australias horticulture through in-farm management, monitoring to demonstrate pest freedom, quarantine and trade restrictions, and crop losses. Here, we used a common species distribution modelling approach, Maxent, to assess habitat suitability for these 11 species under current and future climate scenarios. These projections indicate that the Wet Tropics is likely to be vulnerable to all 11 species. The east coast of Australia will likely remain vulnerable to multiple species until at least 2070. Both the Cape York Peninsula and Northern Territory are also likely to be vulnerable, however, extrapolation to novel climates in these areas decrease confidence in model projections. The climate suitability of current major horticulture regions in north-western Australia, the Northern Territory, southern-central regions of New South Wales and southern Victoria to these pests is projected to increase as climate changes. Our study highlights areas at risk of pest range expansion in the future, to guide Australias horticulture industry in developing effective monitoring and management strategies.

ecology↗

bioRxiv2018

Helicase Promotes Replication Re-initiation from an RNA Transcript

To ensure accurate DNA replication, a replisome must effectively overcome numerous obstacles on its DNA substrate. After encountering an obstacle, a progressing replisome often aborts DNA synthesis but continues to unwind the DNA, resulting in a gap in the newly replicated DNA. However, little is known about how DNA synthesis is resumed downstream of an obstacle. Here, we examine the consequences of a non-replicating replisome collision with a co-directional RNA polymerase (RNAP). Using single-molecule and ensemble methods, we find that T7 helicase interacts strongly with a non-replicating T7 DNA polymerase (DNAP) at a replication fork. As the helicase advances the fork, the DNAP also moves forward processively, via its association with the helicase. The presence of the DNAP, in turn, increases both helicases processivity and unwinding rate. We show that such a DNAP, together with its helicase, is indeed able to actively disrupt a stalled transcription elongation complex, and then initiates replication using the RNA transcript as a primer. These observations exhibit T7 helicases novel role in replication re-initiation, independent of replication restart proteins or primase.

biophysics↗