Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Gaballa, Ahmed; Helmann, John D.

doi:10.1099/mic.0.053579-0

Cited by 19 publications

(24 citation statements)

References 48 publications

(94 reference statements)

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“…It is possible that the infected cells have higher iron requirements that could explain the high transcripts levels detected for dhbF and also for yetG (Table 1). YetG (also called HmoA) is a heme-degrading monooxygenase that is able to degrade the heme group, releasing the iron (33).…”

Section: Resultsmentioning

confidence: 99%

Global Transcriptional Analysis of Virus-Host Interactions between Phage ϕ29 and Bacillus subtilis

Mojardín

Salas

2016

J Virol

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The study of phage-host relationships is essential to understanding the dynamic of microbial systems. Here, we analyze genomewide interactions of Bacillus subtilis and its lytic phage 29 during the early stage of infection. Simultaneous high-resolution analysis of virus and host transcriptomes by deep RNA sequencing allowed us to identify differentially expressed bacterial genes. Phage 29 induces significant transcriptional changes in about 0.9% (38/4,242) and 1.8% (76/4,242) of the host protein-coding genes after 8 and 16 min of infection, respectively. Gene ontology enrichment analysis clustered upregulated genes into several functional categories, such as nucleic acid metabolism (including DNA replication) and protein metabolism (including translation). Surprisingly, most of the transcriptional repressed genes were involved in the utilization of specific carbon sources such as ribose and inositol, and many contained promoter binding-sites for the catabolite control protein A (CcpA). Another interesting finding is the presence of previously uncharacterized antisense transcripts complementary to the well-known phage 29 messenger RNAs that adds an additional layer to the viral transcriptome complexity. IMPORTANCEThe specific virus-host interactions that allow phages to redirect cellular machineries and energy resources to support the viral progeny production are poorly understood. This study provides, for the first time, an insight into the genome-wide transcriptional response of the Gram-positive model Bacillus subtilis to phage 29 infection. Due to their small dimension and limited size of genomes, bacteriophages have optimized the exploitation of host resources to increase the production of the viral progeny. A comprehensive understanding of these host-virus interactions requires the analysis of associated transcriptional changes in both organisms. Thus, we used the recently developed RNA sequencing (RNA-Seq) technology to monitor to a high level of accuracy and depth the genome-wide effect of the bacteriophage 29 on Bacillus subtilis transcription. The transcriptome profiles were analyzed at two early infection time points (8 and 16 min postinfection) so that the identification of the bacterial genes corresponding to these stages could allow the identification of potential phage targets.Phage 29 is a well-characterized lytic virus that belongs to the Podoviridae family. Over the years, it has been the subject of many extensive studies that have contributed to the understanding of several molecular mechanisms of biological processes, such as transcription regulation, viral DNA packaging, viral morphogenesis, and DNA replication (1). Phage 29 genome consists of a linear double-stranded DNA (dsDNA) molecule of 19,285 bp, which encodes 28 open reading frames (ORFs) transcribed from four early and one late promoters. The viral genes are expressed in a temporal sequence to ensure that DNA replication, and the production and assembly of viral components occur in an orderly fashion. Thus, bacterial cells inf...

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Section: Resultsmentioning

confidence: 99%

Global Transcriptional Analysis of Virus-Host Interactions between Phage ϕ29 and Bacillus subtilis

Mojardín

Salas

2016

J Virol

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“…The Bacillus subtilis Fur regulon includes ϳ40 proteins expressed in response to iron deprivation and the small regulatory RNA (sRNA) FsrA (4,27). The derepressed proteins include enzymes for the synthesis of bacillibactin (a catecholate siderophore), several ABC transporters for the import of ferric-bacillibactin and other ferricsiderophore complexes, two flavodoxins, and additional proteins with uncertain relevance to iron homeostasis (28,52,54,58). The derepression of the FsrA sRNA and three coregulated accessory proteins (FbpA, FbpB, FbpC) serves to downregulate low-priority iron-utilizing enzymes in times of iron deficiency (27).…”

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confidence: 99%

Derepression of the Bacillus subtilis PerR Peroxide Stress Response Leads to Iron Deficiency

Faulkner

Fuangthong

et al. 2011

Journal of Bacteriology

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The Bacillus subtilis PerR repressor regulates the adaptive response to peroxide stress. The PerR regulon includes the major vegetative catalase (katA), an iron storage protein (mrgA), an alkylhydroperoxide reductase (ahpCF), a zinc uptake system (zosA), heme biosynthesis enzymes (hemAXCDBL), the iron uptake repressor (fur), and perR itself. A perR null strain is resistant to hydrogen peroxide, accumulates a porphyrin-like compound, and grows very slowly. The poor growth of the perR mutant can be largely accounted for by the elevated expression of two proteins: the KatA catalase and Fur. Genetic studies support a model in which poor growth of the perR null mutant is due to elevated repression of iron uptake by Fur, exacerbated by heme sequestration by the abundant catalase protein. Analysis of the altered-function allele perR991 further supports a link between PerR and iron homeostasis. Strains containing perR991 are peroxide resistant but grow nearly as well as the wild type. Unlike a perR null allele, the perR991 allele (F51S) derepresses KatA, but not Fur, which likely accounts for its comparatively rapid growth.

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“…subtilis does encode two heme monooxygenases, HmoA and HmoB, that bind and degrade heme in vitro, although a physiological role for these proteins has not yet been demonstrated [23]. HmoB belongs to the well-characterized IsdG family and is not regulated by Fe(II), whereas the Fur-regulated HmoA protein represents a poorly characterized subgroup of monooxygenases found in several pathogenic bacteria [23,24]. Since Zn(II) intoxication leads to heme accumulation, we reasoned that HmoA and HmoB may contribute to Zn(II) tolerance.…”

Section: Resultsmentioning

confidence: 99%

Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

Chandrangsu

Helmann

2016

PLoS Genet

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Transition metal ions (Zn(II), Cu(II)/(I), Fe(III)/(II), Mn(II)) are essential for life and participate in a wide range of biological functions. Cellular Zn(II) levels must be high enough to ensure that it can perform its essential roles. Yet, since Zn(II) binds to ligands with high avidity, excess Zn(II) can lead to protein mismetallation. The major targets of mismetallation, and the underlying causes of Zn(II) intoxication, are not well understood. Here, we use a forward genetic selection to identify targets of Zn(II) toxicity. In wild-type cells, in which Zn(II) efflux prevents intoxication of the cytoplasm, extracellular Zn(II) inhibits the electron transport chain due to the inactivation of the major aerobic cytochrome oxidase. This toxicity can be ameliorated by depression of an alternate oxidase or by mutations that restrict access of Zn(II) to the cell surface. Conversely, efflux deficient cells are sensitive to low levels of Zn(II) that do not inhibit the respiratory chain. Under these conditions, intracellular Zn(II) accumulates and leads to heme toxicity. Heme accumulation results from dysregulation of the regulon controlled by PerR, a metal-dependent repressor of peroxide stress genes. When metallated with Fe(II) or Mn(II), PerR represses both heme biosynthesis (hemAXCDBL operon) and the abundant heme protein catalase (katA). Metallation of PerR with Zn(II) disrupts this coordination, resulting in depression of heme biosynthesis but continued repression of catalase. Our results support a model in which excess heme partitions to the membrane and undergoes redox cycling catalyzed by reduced menaquinone thereby resulting in oxidative stress.

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Bacillus subtilis Fur represses one of two paralogous haem-degrading monooxygenases

Cited by 19 publications

References 48 publications

Global Transcriptional Analysis of Virus-Host Interactions between Phage ϕ29 and Bacillus subtilis

Global Transcriptional Analysis of Virus-Host Interactions between Phage ϕ29 and Bacillus subtilis

Derepression of the Bacillus subtilis PerR Peroxide Stress Response Leads to Iron Deficiency

Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

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