scholarly journals The Enhancer Binding Protein Nla6 Regulates Developmental Genes That Are Important for Myxococcus xanthus Sporulation

2015 ◽  
Vol 197 (7) ◽  
pp. 1276-1287 ◽  
Author(s):  
Krista M. Giglio ◽  
Chengjun Zhu ◽  
Courtney Klunder ◽  
Shelley Kummer ◽  
Anthony G. Garza
Keyword(s):  
Binding Site ◽  
Developmental Process ◽  
Myxococcus Xanthus ◽  
Direct Repeat ◽  
Resistant Cell ◽  
Content Type ◽  
Body Development ◽  
Signal Production

ABSTRACTIn the bacteriumMyxococcus xanthus, starvation triggers the formation of multicellular fruiting bodies containing thousands of stress-resistant spores. Recent work showed that fruiting body development is regulated by a cascade of transcriptional activators called enhancer binding proteins (EBPs). The EBP Nla6 is a key component of this cascade; it regulates the promoters of other EBP genes, including a downstream-functioning EBP gene that is crucial for sporulation. In recent expression studies, hundreds of Nla6-dependent genes were identified, suggesting that the EBP gene targets of Nla6 may be part of a much larger regulon. The goal of this study was to identify and characterize genes that belong to the Nla6 regulon. Accordingly, a direct repeat [consensus, C(C/A)ACGNNGNC] binding site for Nla6 was identified usingin vitroandin vivomutational analyses, and the sequence was subsequently used to find 40 potential developmental promoter (88 gene) targets. We showed that Nla6 binds to the promoter region of four new targets (asgE,exo, MXAN2688, and MXAN3259)in vitroand that Nla6 is important for their normal expressionin vivo. Phenotypic studies indicate that all of the experimentally confirmed targets of Nla6 are primarily involved in sporulation. These targets include genes involved in transcriptional regulation, cell-cell signal production, and spore differentiation and maturation. Although sporulation occurs late in development, all of the developmental loci analyzed here show an Nla6-dependent burst in expression soon after starvation is induced. This finding suggests that Nla6 starts preparing cells for sporulation very early in the developmental process.IMPORTANCEBacterial development yields a remarkable array of complex multicellular forms. One such form, which is commonly found in nature, is a surface-associated aggregate of cells known as a biofilm. Mature biofilms are structurally complex and contain cells that are highly resistant to antibacterial agents. When starving, the model bacteriumMyxococcus xanthusforms a biofilm containing a thin mat of cells and multicellular structures that house a highly resistant cell type called a myxospore. Here, we identify the promoter binding site of the transcriptional activator Nla6, identify genes in the Nla6 regulon, and show that several of the genes in the Nla6 regulon are important for production of stress-resistant spores in starvation-inducedM. xanthusbiofilms.

scholarly journals An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases inMyxococcus xanthusDK1622

2018 ◽  
Vol 200 (21) ◽  
Author(s):  
Karla J. Esquilín-Lebrón ◽  
Tye O. Boynton ◽  
Lawrence J. Shimkets ◽  
Michael G. Thomas
Keyword(s):  
Myxococcus Xanthus ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases

ABSTRACTOne mechanism by which bacteria and fungi produce bioactive natural products is the use of nonribosomal peptide synthetases (NRPSs). Many NRPSs in bacteria require members of the MbtH-like protein (MLP) superfamily for their solubility or function. Although MLPs are known to interact with the adenylation domains of NRPSs, the role MLPs play in NRPS enzymology has yet to be elucidated. MLPs are nearly always encoded within the biosynthetic gene clusters (BGCs) that also code for the NRPSs that interact with the MLP. Here, we identify 50 orphan MLPs from diverse bacteria. An orphan MLP is one that is encoded by a gene that is not directly adjacent to genes predicted to be involved in nonribosomal peptide biosynthesis. We targeted the orphan MLP MXAN_3118 fromMyxococcus xanthusDK1622 for characterization. TheM. xanthusDK1622 genome contains 15 NRPS-encoding BGCs but only one MLP-encoding gene (MXAN_3118). We tested the hypothesis that MXAN_3118 interacts with one or more NRPS using a combination ofin vivoandin vitroassays. We determined that MXAN_3118 interacts with at least seven NRPSs from distinct BGCs. We show that one of these BGCs codes for NRPS enzymology that likely produces a valine-rich natural product that inhibits the clumping ofM. xanthusDK1622 in liquid culture. MXAN_3118 is the first MLP to be identified that naturally interacts with multiple NRPS systems in a single organism. The finding of an MLP that naturally interacts with multiple NRPS systems suggests it may be harnessed as a “universal” MLP for generating functional hybrid NRPSs.IMPORTANCEMbtH-like proteins (MLPs) are essential accessory proteins for the function of many nonribosomal peptide synthetases (NRPSs). We identified 50 MLPs from diverse bacteria that are coded by genes that are not located near any NRPS-encoding biosynthetic gene clusters (BGCs). We define these as orphan MLPs because their NRPS partner(s) is unknown. Investigations into the orphan MLP fromMyxococcus xanthusDK1622 determined that it interacts with NRPSs from at least seven distinct BGCs. Support for these MLP-NRPS interactions came from the use of a bacterial two-hybrid assay and copurification of the MLP with various NRPSs. The flexibility of this MLP to naturally interact with multiple NRPSs led us to hypothesize that this MLP may be used as a “universal” MLP during the construction of functional hybrid NRPSs.

scholarly journals WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System

2016 ◽  
Vol 198 (8) ◽  
pp. 1281-1293 ◽  
Author(s):  
Julien Herrou ◽  
Daniel M. Czyż ◽  
Jonathan W. Willett ◽  
Hye-Sook Kim ◽  
Gekleng Chhor ◽  
...  
Keyword(s):  
Stress Response ◽  
Mouse Model ◽  
Binding Site ◽  
Brucella Abortus ◽  
Chronic Infection ◽  
Content Type ◽  
General Stress Response ◽  
General Stress

ABSTRACTThe general stress response (GSR) system of the intracellular pathogenBrucella abortuscontrols the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required forB. abortussurvival under nonoptimal growth conditionsin vitroand for maintenance of chronic infection in anin vivomouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined.bab1_1070is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditionsin vitro. We have solved crystal structures of Bab1_1070 and demonstrate that it forms a homotetrameric complex that resembles those of WrbA-type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However,B. abortusWrbA-relatedprotein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductasein vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion ofwrpA(ΔwrpA) does not compromise cell survival under acute oxidative stressin vitroor attenuate infection in cell-based or mouse models. However, a ΔwrpAstrain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulatesB. abortusinteraction with its mammalian host. Despite high structural homology with canonical WrbA proteins, we propose thatB. abortusWrpA represents a functionally distinct member of the diverse flavodoxin family.IMPORTANCEBrucella abortusis an etiological agent of brucellosis, which is among the most common zoonotic diseases worldwide. The general stress response (GSR) regulatory system ofB. abortuscontrols the transcription of approximately 100 genes and is required for maintenance of chronic infection in a murine model; the majority of GSR-regulated genes remain uncharacterized. We presentin vitroandin vivofunctional and structural analyses of WrpA, whose expression is strongly induced by GSR under oxidative conditions. Though WrpA is structurally related to NADH:quinone oxidoreductases, it does not bind redox cofactors in solution, nor does it exhibit oxidoreductase activityin vitro. However, WrpA does affect spleen inflammation in a murine infection model. Our data provide evidence that WrpA forms a new functional class of WrbA/flavodoxin family proteins.

scholarly journals Transcriptional Repression of the VC2105 Protein by Vibrio FadR Suggests that It Is a New Auxiliary Member of thefadRegulon

2016 ◽  
Vol 82 (9) ◽  
pp. 2819-2832 ◽  
Author(s):  
Rongsui Gao ◽  
Jingxia Lin ◽  
Han Zhang ◽  
Youjun Feng
Keyword(s):  
Transcriptional Regulation ◽  
Fatty Acid ◽  
Ligand Binding ◽  
Binding Site ◽  
Binding Sites ◽  
Regulatory Proteins ◽  
Content Type ◽  
Ligand Binding Sites

ABSTRACTRecently, our group along with others reported that theVibrioFadR regulatory protein is unusual in that, unlike the prototypicalfadRproduct ofEscherichia coli, which has only one ligand-binding site,VibrioFadR has two ligand-binding sites and represents a new mechanism for fatty acid sensing. The promoter region of thevc2105gene, encoding a putative thioesterase, was mapped, and a putative FadR-binding site (AA CTG GTA AGA GCA CTT) was proposed. Different versions of the FadR regulatory proteins were prepared and purified to homogeneity. Both electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR) determined the direct interaction of thevc2105gene with FadR proteins of various origins. Further, EMSAs illustrated that the addition of long-chain acyl-coenzyme A (CoA) species efficiently dissociates thevc2105promoter from the FadR regulator. The expression level of theVibrio cholerae vc2105gene was elevated 2- to 3-fold in afadRnull mutant strain, validating that FadR is a repressor for thevc2105gene. The β-galactosidase activity of avc2105-lacZtranscriptional fusion was increased over 2-fold upon supplementation of growth medium with oleic acid. Unlike thefadDgene, a member of theVibrio fadregulon, the VC2105 protein played no role in bacterial growth and virulence-associated gene expression ofctxAB(cholera toxin A/B) andtcpA(toxin coregulated pilus A). Given that the transcriptional regulation ofvc2105fits the criteria for fatty acid degradation (fad) genes, we suggested that it is a new member of theVibrio fadregulon.IMPORTANCETheVibrioFadR regulator is unusual in that it has two ligand-binding sites. Different versions of the FadR regulatory proteins were prepared and characterizedin vitroandin vivo. An auxiliaryfadgene (vc2105) fromVibriowas proposed that encodes a putative thioesterase and has a predicted FadR-binding site (AAC TGG TA A GAG CAC TT). The function of this putative binding site was proved using both EMSA and SPR. Furtherin vitroandin vivoexperiments revealed that theVibrioFadR is a repressor for thevc2105gene. UnlikefadD, a member of theVibrio fadregulon, VC2105 played no role in bacterial growth and expression of the two virulence-associated genes (ctxABandtcpA). Therefore, since transcriptional regulation ofvc2105fits the criteria forfadgenes, it seems likely thatvc2105acts as a new auxiliary member of theVibrio fadregulon.

scholarly journals Combinatorial Regulation by a Novel Arrangement of FruA and MrpC2 Transcription Factors during Myxococcus xanthus Development

2009 ◽  
Vol 191 (8) ◽  
pp. 2753-2763 ◽  
Author(s):  
Sheenu Mittal ◽  
Lee Kroos
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Promoter Region ◽  
Developmental Process ◽  
Response Regulator ◽  
Myxococcus Xanthus ◽  
Control Cell ◽  
Cooperative Binding ◽  
Regulatory Sequence

ABSTRACT Myxococcus xanthus is a gram-negative soil bacterium that undergoes multicellular development upon nutrient limitation. Intercellular signals control cell movements and regulate gene expression during the developmental process. C-signal is a short-range signal essential for aggregation and sporulation. C-signaling regulates the fmgA gene by a novel mechanism involving cooperative binding of the response regulator FruA and the transcription factor/antitoxin MrpC2. Here, we demonstrate that regulation of the C-signal-dependent fmgBC operon is under similar combinatorial control by FruA and MrpC2, but the arrangement of binding sites is different than in the fmgA promoter region. MrpC2 was shown to bind to a crucial cis-regulatory sequence in the fmgBC promoter region. FruA was required for MrpC and/or MrpC2 to associate with the fmgBC promoter region in vivo, and expression of an fmgB-lacZ fusion was abolished in a fruA mutant. Recombinant FruA was shown to bind to an essential regulatory sequence located slightly downstream of the MrpC2-binding site in the fmgBC promoter region. Full-length FruA, but not its C-terminal DNA-binding domain, enhanced the formation of complexes with fmgBC promoter region DNA, when combined with MrpC2. This effect was nearly abolished with fmgBC DNA fragments having a mutation in either the MrpC2- or FruA-binding site, indicating that binding of both proteins to DNA is important for enhancement of complex formation. These results are similar to those observed for fmgA, where FruA and MrpC2 bind cooperatively upstream of the promoter, except that in the fmgA promoter region the FruA-binding site is located slightly upstream of the MrpC2-binding site. Cooperative binding of FruA and MrpC2 appears to be a conserved mechanism of gene regulation that allows a flexible arrangement of binding sites and coordinates multiple signaling pathways.

scholarly journals Engineering Pseudochelin Production inMyxococcus xanthus

2018 ◽  
Vol 84 (22) ◽  
Author(s):  
Juliane Korp ◽  
Lea Winand ◽  
Angela Sester ◽  
Markus Nett
Keyword(s):  
Iron Homeostasis ◽  
Condensation Reaction ◽  
Myxococcus Xanthus ◽  
Inducible Promoter ◽  
Content Type ◽  
Intramolecular Condensation ◽  
Amidohydrolase Superfamily ◽  
Interesting Alternative

ABSTRACTMyxobacteria utilize the catechol natural products myxochelin A and B in order to maintain their iron homeostasis. Recently, the production of these siderophores, along with a new myxochelin derivative named pseudochelin A, was reported for the marine bacteriumPseudoalteromonas piscicidaS2040. The latter derivative features a characteristic imidazoline moiety, which was proposed to originate from an intramolecular condensation reaction of the β-aminoethyl amide group in myxochelin B. To identify the enzyme catalyzing this conversion, we compared the myxochelin regulons of two myxobacterial strains that produce solely myxochelin A and B with those ofP. piscicidaS2040. This approach revealed a gene exclusive to the myxochelin regulon inP. piscicidaS2040, coding for an enzyme of the amidohydrolase superfamily. To prove that this enzyme is indeed responsible for the postulated conversion, the reaction was reconstitutedin vitrousing a hexahistidine-tagged recombinant protein made inEscherichia coli, with myxochelin B as the substrate. To test the production of pseudochelin A underin vivoconditions, the amidohydrolase gene was cloned into the myxobacterial plasmid pZJY156 and placed under the control of a copper-inducible promoter. The resulting vector was introduced into the myxobacteriumMyxococcus xanthusDSM 16526, a native producer of myxochelin A and B. Following induction with copper, the myxobacterial expression strain was found to synthesize small quantities of pseudochelin A. Replacement of the copper-inducible promoter with the constitutivepilApromoter led to increased production levels inM. xanthus, which facilitated the isolation and subsequent structural verification of the heterologously produced compound.IMPORTANCEIn this study, an enzyme for imidazoline formation in pseudochelin biosynthesis was identified. Evidence for the involvement of this enzyme in the postulated reaction was obtained afterin vitroreconstitution. Furthermore, the function of this enzyme was demonstratedin vivoby transferring the corresponding gene into the bacteriumMyxococcus xanthus, which thereby became a producer of pseudochelin A. In addition to clarifying the molecular basis of imidazoline formation in siderophore biosynthesis, we describe the heterologous expression of a gene in a myxobacterium without chromosomal integration. Due to its metabolic proficiency,M. xanthusrepresents an interesting alternative to established host systems for the reconstitution and manipulation of biosynthetic pathways. Since the plasmid used in this study is easily adaptable for the expression of other enzymes as well, we expand the conventional expression strategy for myxobacteria, which is based on the integration of biosynthetic genes into the host genome.

scholarly journals Nucleotides Critical for the Interaction of the Streptococcus pyogenes Mga Virulence Regulator with Mga-Regulated Promoter Sequences

2012 ◽  
Vol 194 (18) ◽  
pp. 4904-4919 ◽  
Author(s):  
Lara L. Hause ◽  
Kevin S. McIver
Keyword(s):  
Binding Site ◽  
Streptococcus Pyogenes ◽  
Transcriptional Activation ◽  
Luciferase Reporter ◽  
Mobility Shift ◽  
Content Type ◽  
Promoter Sequences ◽  
Mobility Shift Assay

ABSTRACTThe Mga regulator ofStreptococcus pyogenesdirectly activates the transcription of a core regulon that encodes virulence factors such as M protein (emm), C5a peptidase (scpA), and streptococcal inhibitor of complement (sic) by directly binding to a 45-bp binding site as determined by an electrophoretic mobility shift assay (EMSA) and DNase I protection. However, by comparing the nucleotide sequences of all established Mga binding sites, we found that they exhibit only 13.4% identity with no discernible symmetry. To determine the core nucleotides involved in functional Mga-DNA interactions, the M1T1 Pemm1binding site was altered and screened for nucleotides important for DNA bindingin vitroand for transcriptional activation using a plasmid-based luciferase reporterin vivo. Following this analysis, 34 nucleotides within the Pemm1binding site that had an effect on Mga binding, Mga-dependent transcriptional activation, or both were identified. Of these critical nucleotides, guanines and cytosines within the major groove were disproportionately identified clustered at the 5′ and 3′ ends of the binding site and with runs of nonessential adenines between the critical nucleotides. On the basis of these results, a Pemm1minimal binding site of 35 bp bound Mga at a level comparable to the level of binding of the larger 45-bp site. Comparison of Pemmwith directed mutagenesis performed in the M1T1 Mga-regulated PscpAand Psicpromoters, as well as methylation interference analysis of PscpA, establish that Mga binds to DNA in a promoter-specific manner.

scholarly journals Adenylate Charge Regulates Sensor Kinase CheS3 To Control Cyst Formation in Rhodospirillum centenum

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Kuang He ◽  
Vladimira Dragnea ◽  
Carl E. Bauer
Keyword(s):  
Histidine Kinase ◽  
Developmental Process ◽  
Cyst Formation ◽  
Molar Ratio ◽  
Content Type ◽  
Rhodospirillum Centenum ◽  
Cellular Energy ◽  
Hybrid Histidine Kinase

ABSTRACTRhodospirillum centenumforms metabolically dormant cysts under unfavorable growth conditions such as desiccation or nutrient starvation. The development of cysts is tightly regulated and involves a cyst-repressing chemotaxis-like signal transduction pathway called the Che3signaling cascade. The Che3cascade is comprised of a methyl chemoreceptor (MCP3), receptor-methylating/demethylating proteins CheB3and CheR3, two CheW3linker proteins, a CheA3-CheY hybrid histidine kinase, and a single-domain response regulator, CheY3. In addition to Che-like components, the Che3cascade also contains a second hybrid histidine kinase, CheS3. Recent biochemical and genetic studies show that CheA3does not serve as a phosphor donor for CheY3; instead, CheA3inhibits a CheS3→CheY3two-component system by phosphorylating an inhibitory receiver domain of CheS3. In this study, we show that in addition to phosphorylation by CheA3, the phosphorylation state of CheS3is also regulated by the cellular energy level as quantified by the molar ratio of ATP/(ATP + ADP). A 35% decrease in cellular energy is shown to occurin vivoupon a nutrient downshift that gives rise to cyst formation. When this energy decline is replicatedin vitro, the phosphorylation level of CheS3is reduced by ~75%. Finally, we also show that ADP-mediated reduction of CheS3phosphorylation is a consequence of ADP enhancing autodephosphorylation of CheS3.IMPORTANCEUpon starvation,Rhodospirillum centenumundergoes a developmental process that forms metabolically dormant cysts, which withstand desiccation and nutritional limitation. This study explores the role of the cellular energy state as measured by the ratio of ATP to ADP as an important regulator of cyst formation inRhodospirillum centenum. We show thatR. centenumcells experience a significant reduction in ATP during cyst formation using ATP/(ATP + ADP) as a measurement. When thisin vivolevel of energy starvation is simulatedin vitro, CheS3phosphorylation is reduced by 75%. This profound reduction in CheS3autophosphorylation is contrasted with a much lower 25% decrease in CheA3phosphorylation in response to a similar downward shift in ATP/(ATP + ADP). We argue that even though adenylate energy affects all ATP-dependent enzymes to an extent, the enhanced inhibition of CheS3activity in response to a reduction in the ATP/(ATP + ADP) ratio likely functions as an important input signal to regulate cyst development.

scholarly journals Combinatorial Regulation of thedevOperon by MrpC2 and FruA during Myxococcus xanthus Development

2014 ◽  
Vol 197 (2) ◽  
pp. 240-251 ◽  
Author(s):  
Ashleigh Campbell ◽  
Poorna Viswanathan ◽  
Terry Barrett ◽  
Bongjun Son ◽  
Shreya Saha ◽  
...  
Keyword(s):  
Myxococcus Xanthus ◽  
Developmental Expression ◽  
Cooperative Binding ◽  
Fruiting Bodies ◽  
Content Type ◽  
Combinatorial Regulation ◽  
Proximal Site ◽  
A Site

Proper expression of thedevoperon is important for normal development ofMyxococcus xanthus. When starved, these bacteria coordinate their gliding movements to build mounds that become fruiting bodies as some cells differentiate into spores. Mutations in thedevTRSgenes impair sporulation. Expression of the operon occurs within nascent fruiting bodies and depends in part on C signaling. Here, we report that expression of thedevoperon, like that of several other C-signal-dependent genes, is subject to combinatorial control by the transcription factors MrpC2 and FruA. A DNA fragment upstream of thedevpromoter was bound by a protein in an extract containing MrpC2, protecting the region spanning positions −77 to −54. Mutations in this region impaired binding of purified MrpC2 and abolished developmental expression of reporter fusions. The association of MrpC2 and/or its longer form, MrpC, with thedevpromoter region depended on FruAin vivo, based on chromatin immunoprecipitation analysis, and purified FruA appeared to bind cooperatively with MrpC2 to DNA just upstream of thedevpromoterin vitro. We conclude that cooperative binding of the two proteins to this promoter-proximal site is crucial fordevexpression. 5′ deletion analysis implied a second upstream positive regulatory site, which corresponded to a site of weak cooperative binding of MrpC2 and FruA and boosteddevexpression 24 h into development. This site is unique among the C-signal-dependent genes studied so far. Deletion of this site in theM. xanthuschromosome did not impair sporulation under laboratory conditions.

scholarly journals Aag Hypoxanthine-DNA Glycosylase Is Synthesized in the Forespore Compartment and Involved in Counteracting the Genotoxic and Mutagenic Effects of Hypoxanthine and Alkylated Bases in DNA during Bacillus subtilis Sporulation

2016 ◽  
Vol 198 (24) ◽  
pp. 3345-3354 ◽  
Author(s):  
Víctor M. Ayala-García ◽  
Luz I. Valenzuela-García ◽  
Peter Setlow ◽  
Mario Pedraza-Reyes
Keyword(s):  
Bacillus Subtilis ◽  
Developmental Process ◽  
Specific Pattern ◽  
Dna Glycosylase ◽  
Regulatory Sequences ◽  
Regulation Of Expression ◽  
Content Type ◽  
Mutagenic Effects

ABSTRACTAag fromBacillus subtilishas been implicated inin vitroremoval of hypoxanthine and alkylated bases from DNA. The regulation of expression ofaaginB. subtilisand the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptionalaag-lacZfusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably,aag-lacZexpression was higher inside the forespore than in the mother cell compartment, and this expression was abolished in asigG-deficient background, suggesting a forespore-specific mechanism ofaagtranscription. Two additional findings supported this suggestion: (i) expression of anaag-yfpfusion was observed in the forespore, and (ii)in vivomapping of theaagtranscription start site revealed the existence of upstream regulatory sequences possessing homology to σG-dependent promoters. In comparison with the wild-type strain, disruption ofaagsignificantly reduced survival of sporulatingB. subtiliscells following nitrous acid or methyl methanesulfonate treatments, and the Rifrmutation frequency was significantly increased in anaagstrain. These results suggest that Aag protects the genome of developingB. subtilissporangia from the cytotoxic and genotoxic effects of base deamination and alkylation.IMPORTANCEIn this study, evidence is presented revealing thataag, encoding a DNA glycosylase implicated in processing of hypoxanthine and alkylated DNA bases, exhibits a forespore-specific pattern of gene expression duringB. subtilissporulation. Consistent with this spatiotemporal mode of expression, Aag was found to protect the sporulating cells of this microorganism from the noxious and mutagenic effects of base deamination and alkylation.

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