Biology subjects

Zheng, V.

Publications and source records attributed to Zheng, V..

3 recordsLinked to original sources

bioRxiv2024

The Staphylococcus aureus small non-coding RNA IsrR regulates TCA cycle activity and virulence

Staphylococcus aureus has evolved mechanisms to cope with low iron (Fe) availability in host tissues. S. aureus uses the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that an S. aureus {Delta}fur mutant has decreased expression of acnA, which codes for the Fe-dependent enzyme aconitase. Decreased acnA expression prevented the {Delta}fur mutant from growing with amino acids as sole carbon and energy sources. Suppressor analysis determined that a mutation in isrR, which produces a regulatory RNA, permitted growth by decreasing isrR transcription. The decreased AcnA activity of the {Delta}fur mutant was partially relieved by an {Delta}isrR mutation. Directed mutation of bases predicted to facilitate the interaction between the acnA transcript and IsrR, decreased the ability of IsrR to control acnA expression in vivo and IsrR bound to the acnA transcript in vitro. IsrR also bound to the transcripts coding the alternate TCA cycle proteins sdhC, mqo, citZ, and citM. Whole cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/601953v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1ec27b2org.highwire.dtl.DTLVardef@1224b64org.highwire.dtl.DTLVardef@83cd49org.highwire.dtl.DTLVardef@11a9cea_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

YlaN is an iron(II) binding protein that functions to relieve Fur-mediated repression of gene expression in Staphylococcus aureus

Iron (Fe) is a trace nutrient required by nearly all organisms. As a result of the demand for Fe and the toxicity of non-chelated cytosolic ionic Fe, regulatory systems have evolved to tightly balance Fe acquisition and usage while limiting overload. In most bacteria, including the mammalian pathogen Staphylococcus aureus, the ferric uptake regulator (Fur) is the primary transcriptional regulator that controls the transcription of genes that code for Fe uptake and utilization proteins. YlaN was demonstrated to be essential in Bacillus subtilis unless excess Fe is added to the growth medium, suggesting a role in Fe homeostasis. Here, we demonstrate that YlaN is expendable in S. aureus; however, YlaN became essential upon Fe deprivation. A null fur allele bypassed the essentiality of YlaN. The transcriptional response of Fur derepression resulted in a reprogramming of metabolism to prioritize fermentative growth over respiratory growth. The absence of YlaN diminished the derepression of Fur-dependent transcription during Fe limitation. Bioinformatic analyses suggest that ylaN was recruited to Gram positive bacteria and once acquired was maintained in the genome as it co-evolved with Fur. Consistent with a role for YlaN in influencing Fur-dependent regulation, YlaN and Fur interacted in vivo. YlaN bound Fe(II) in vitro using oxygen or nitrogen ligands with an association constant that is consistent with a physiological role in Fe sensing and/or buffering. These findings have led to a model wherein YlaN is an Fe(II) binding protein that influences Fur-dependent regulation through direct interaction. ImportanceIron (Fe) is an essential nutrient for nearly all organisms. If Fe homeostasis is not maintained, Fe can accumulate in the cytosol where it is toxic. Questions remain about how cells efficiently balance Fe uptake and usage to prevent imbalance. Iron uptake and proper metalation of proteins are essential processes in the mammalian bacterial pathogen Staphylococcus aureus. Understanding the gene products involved in Fe ion regulation, uptake, and usage, as well as the physiological adaptations that S. aureus uses to survive in Fe-depleted conditions, will provide insight into the role that Fe has in pathogenesis. These data will also provide insight into the selective pressures imparted by the mammalian host.

microbiology↗

bioRxiv2020

Identifying Taxonomic Units in Metagenomic DNA Streams

With the emergence of portable DNA sequencers, such as Oxford Nanopore Technology MinION, metagenomic DNA sequencing can be performed in real-time and directly in the field. However, because metagenomic DNA analysis is computationally and memory intensive, and the current methods are designed for batch processing, the current metagenomic tools are not well suited for mobile devices. In this paper, we propose a new memory-efficient method to identify Operational Taxonomic Units (OTUs) in metagenomic DNA streams. Our method is based on finding connected components in overlap graphs constructed over a real-time stream of long DNA reads as produced by MinION platform. We propose an efficient algorithm to maintain connected components when an overlap graph is streamed, and show how redundant information can be removed from the stream by transitive closures. Through experiments on simulated and real-world metagenomic data, we demonstrate that the resulting solution is able to recover OTUs with high precision while remaining suitable for mobile computing devices.

bioinformatics↗