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818800.8917Biofilm in implant infections: its production and regulation. A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intraocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.A significant proportion of medical implants become the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms. Biofilm is a microbial derived sessile community characterized by cells that are irreversibly attached to a substratum or interface to each other, embedded in a matrix of extracellular polymeric substances that they have produced. Bacterial adherence and biofilm production proceed in two steps: first, an attachment to a surface and, second, a cell-to-cell adhesion, with pluristratification of bacteria onto the artificial surface. The first step requires the mediation of bacterial surface proteins, the cardinal of which is similar to S. aureus autolysin and is denominated AtlE. In staphylococci the matrix of extracellular polymeric substances of biofilm is a polymer of beta-1,6-linked N-acetylglucosamine (PIA), whose synthesis is mediated by the ica operon. Biofilm formation is partially controlled by quorum sensing, an interbacterial communication mechanism dependent on population density. The principal implants that can be compromised by biofilm associated infections are: central venous catheters, heart valves, ventricular assist devices, coronary stents, neurosurgical ventricular shunts, implantable neurological stimulators, arthro-prostheses, fracture-fixation devices, inflatable penile implants, breast implants, cochlear implants, intra-ocular lenses, dental implants. Biofilms play an important role in the spread of antibiotic resistance. Within the high dense bacterial population, efficient horizontal transfer of resistance and virulence genes takes place. In the future, treatments that inhibit the transcription of biofilm controlling genes might be a successful strategy in inhibiting these infections.200516353112
510.8769GmRAR1 and GmSGT1 are required for basal, R gene-mediated and systemic acquired resistance in soybean. RAR1, SGT1, and HSP90 are important components of effector-triggered immunity (ETI) in diverse plants, where RAR1 and SGT1 are thought to serve as HSP90 co-chaperones. We show that ETI in soybean requires RAR1 and SGT1 but not HSP90. Rsv1-mediated extreme resistance to Soybean mosaic virus (SMV) and Rpg-1b-mediated resistance to Pseudomonas syringae were compromised in plants silenced for GmRAR1 and GmSGT1-2 but not GmHSP90. This suggests that RAR1- or SGT1-dependant signaling is not always associated with a dependence on HSP90. Unlike in Arabidopsis, SGT1 in soybean also mediates ETI against the bacterial pathogen P. syringae. Similar to Arabidopsis, soybean RAR1 and SGT1 proteins interact with each other and two related HSP90 proteins. Plants silenced for GmHSP90 genes or GmRAR1 exhibited altered morphology, suggesting that these proteins also contribute to developmental processes. Silencing GmRAR1 and GmSGT1-2 impaired resistance to virulent bacteria and systemic acquired resistance (SAR) in soybean as well. Because the Arabidopsis rar1 mutant also showed a defect in SAR, we conclude that RAR1 and SGT1 serve as a point of convergence for basal resistance, ETI, and SAR. We demonstrate that, although soybean defense signaling pathways recruit structurally conserved components, they have distinct requirements for specific proteins.200919061405
1120.8767Diffusible signal factor primes plant immunity against Xanthomonas campestris pv. campestris (Xcc) via JA signaling in Arabidopsis and Brassica oleracea. BACKGROUND: Many Gram-negative bacteria use quorum sensing (QS) signal molecules to monitor their local population density and to coordinate their collective behaviors. The diffusible signal factor (DSF) family represents an intriguing type of QS signal to mediate intraspecies and interspecies communication. Recently, accumulating evidence demonstrates the role of DSF in mediating inter-kingdom communication between DSF-producing bacteria and plants. However, the regulatory mechanism of DSF during the Xanthomonas-plant interactions remain unclear. METHODS: Plants were pretreated with different concentration of DSF and subsequent inoculated with pathogen Xanthomonas campestris pv. campestris (Xcc). Pathogenicity, phynotypic analysis, transcriptome combined with metabolome analysis, genetic analysis and gene expression analysis were used to evaluate the priming effects of DSF on plant disease resistance. RESULTS: We found that the low concentration of DSF could prime plant immunity against Xcc in both Brassica oleracea and Arabidopsis thaliana. Pretreatment with DSF and subsequent pathogen invasion triggered an augmented burst of ROS by DCFH-DA and DAB staining. CAT application could attenuate the level of ROS induced by DSF. The expression of RBOHD and RBOHF were up-regulated and the activities of antioxidases POD increased after DSF treatment followed by Xcc inoculation. Transcriptome combined with metabolome analysis showed that plant hormone jasmonic acid (JA) signaling involved in DSF-primed resistance to Xcc in Arabidopsis. The expression of JA synthesis genes (AOC2, AOS, LOX2, OPR3 and JAR1), transportor gene (JAT1), regulator genes (JAZ1 and MYC2) and responsive genes (VSP2, PDF1.2 and Thi2.1) were up-regulated significantly by DSF upon Xcc challenge. The primed effects were not observed in JA relevant mutant coi1-1 and jar1-1. CONCLUSION: These results indicated that DSF-primed resistance against Xcc was dependent on the JA pathway. Our findings advanced the understanding of QS signal-mediated communication and provide a new strategy for the control of black rot in Brassica oleracea.202337404719
3130.8751miR395-regulated sulfate metabolism exploits pathogen sensitivity to sulfate to boost immunity in rice. MicroRNAs (miRNAs) play important roles in plant physiological activities. However, their roles and molecular mechanisms in boosting plant immunity, especially through the modulation of macronutrient metabolism in response to pathogens, are largely unknown. Here, we report that an evolutionarily conserved miRNA, miR395, promotes resistance to Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), two destructive bacterial pathogens, by regulating sulfate accumulation and distribution in rice. Specifically, miR395 targets and suppresses the expression of the ATP sulfurylase gene OsAPS1, which functions in sulfate assimilation, and two sulfate transporter genes, OsSULTR2;1 and OsSULTR2;2, which function in sulfate translocation, to promote sulfate accumulation, resulting in broad-spectrum resistance to bacterial pathogens in miR395-overexpressing plants. Genetic analysis revealed that miR395-triggered resistance is involved in both pathogen-associated molecular pattern-triggered immunity and R gene-mediated resistance. Moreover, we found that accumulated sulfate but not S-metabolites inhibits proliferation of pathogenic bacteria, revealing a sulfate-mediated antibacterial defense mechanism that differs from sulfur-induced resistance. Furthermore, compared with other bacteria, Xoo and Xoc, which lack the sulfate transporter CysZ, are sensitive to high levels of extracellular sulfate. Accordingly, miR395-regulated sulfate accumulation impaired the virulence of Xoo and Xoc by decreasing extracellular polysaccharide production and biofilm formation. Taken together, these results suggest that rice miR395 modulates sulfate metabolism to exploit pathogen sensitivity to sulfate and thereby promotes broad-spectrum resistance.202234968734
51840.8749Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Two-component systems (TCSs) are key regulatory pathways allowing bacteria to adapt their genetic expression to environmental changes. Bacitracin, a cyclic dodecylpeptide antibiotic, binds to undecaprenyl pyrophosphate, the lipid carrier for cell wall precursors, effectively inhibiting peptidoglycan biosynthesis. We have identified a novel and previously uncharacterized TCS in the major human pathogen Staphylococcus aureus that we show to be essential for bacitracin and nisin resistance: the BraS/BraR system (Bacitracin resistance associated; SA2417/SA2418). The braRS genes are located immediately upstream from genes encoding an ABC transporter, accordingly designated BraDE. We have shown that the BraSR/BraDE module is a key bacitracin and nisin resistance determinant in S. aureus. In the presence of low antibiotic concentrations, BraSR activate transcription of two operons encoding ABC transporters: braDE and vraDE. We identified a highly conserved imperfect palindromic sequence upstream from the braDE and vraDE promoter sequences, essential for their transcriptional activation by BraSR, suggesting it is the likely BraR binding site. We demonstrated that the two ABC transporters play distinct and original roles in antibiotic resistance: BraDE is involved in bacitracin sensing and signalling through BraSR, whereas VraDE acts specifically as a detoxification module and is sufficient to confer bacitracin and nisin resistance when produced on its own. We show that these processes require functional BraD and VraD nucleotide-binding domain proteins, and that the large extracellular loop of VraE confers its specificity in bacitracin resistance. This is the first example of a TCS associated with two ABC transporters playing separate roles in signal transduction and antibiotic resistance.201121696458
58950.8746Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes. Adaptation of the innate immune system has been recently acknowledged, explaining sustained changes of innate immune responses. Such adaptation is termed trained immunity. Trained immunity is initiated by extracellular signals that trigger a cascade of events affecting cell metabolism and mediating chromatin changes on genes that control innate immune responses. Factors demonstrated to facilitate trained immunity are pathogenic signals (fungi, bacteria, viruses) as well non-pathogenic signals such as insulin, cytokines, adipokines or hormones. These signals initiate intracellular signaling cascades that include AKT kinases and mTOR as well as histone methylases and demethylases, resulting in metabolic changes and histone modifications. In the context of insulin resistance, AKT signaling is affected resulting in sustained activation of mTORC1 and enhanced glycolysis. In macrophages elevated glycolysis readily impacts responses to pathogens (bacteria, fungi) or danger signals (TLR-driven signals of tissue damage), partly explaining insulin resistance-related pathologies. Thus, macrophages lacking insulin signaling exhibit reduced responses to pathogens and altered metabolism, suggesting that insulin resistance is a state of trained immunity. Evidence from Insulin Receptor as well as IGF1Receptor deficient macrophages support the contribution of insulin signaling in macrophage responses. In addition, clinical evidence highlights altered macrophage responses to pathogens or metabolic products in patients with systemic insulin resistance, being in concert with cell culture and animal model studies. Herein, we review the current knowledge that supports the impact of insulin signaling and other insulin resistance related signals as modulators of trained immunity.201931244863
62060.8742Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine. Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonization by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common d-sphingosine transcriptomic response of the transient skin colonizer S. aureus and the dominant skin coloniser S. epidermidis. A common d-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to d-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonization of skin where the lipid is present and have implications with topical therapeutic applications.202234902269
61970.8741Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus. Rhodomyrtone (Rom) is an acylphloroglucinol antibiotic originally isolated from leaves of Rhodomyrtus tomentosa. Rom targets the bacterial membrane and is active against a wide range of Gram-positive bacteria but the exact mode of action remains obscure. Here we isolated and characterized a spontaneous Rom-resistant mutant from the model strain Staphylococcus aureus HG001 (Rom(R)) to learn more about the resistance mechanism. We showed that Rom-resistance is based on a single point mutation in the coding region of farR [regulator of fatty acid (FA) resistance] that causes an amino acid change from Cys to Arg at position 116 in FarR, that affects FarR activity. Comparative transcriptome analysis revealed that mutated farR affects transcription of many genes in distinct pathways. FarR represses for example the expression of its own gene (farR), its flanking gene farE (effector of FA resistance), and other global regulators such as agr and sarA. All these genes were consequently upregulated in the Rom(R) clone. Particularly the upregulation of agr and sarA leads to increased expression of virulence genes rendering the Rom(R) clone more cytotoxic and more pathogenic in a mouse infection model. The Rom-resistance is largely due to the de-repression of farE. FarE is described as an efflux pump for linoleic and arachidonic acids. We observed an increased release of lipids in the Rom(R) clone compared to its parental strain HG001. If farE is deleted in the Rom(R) clone, or, if native farR is expressed in the Rom(R) strain, the corresponding strains become hypersensitive to Rom. Overall, we show here that the high Rom-resistance is mediated by overexpression of farE in the Rom(R) clone, that FarR is an important regulator, and that the point mutation in farR (Rom(R) clone) makes the clone hyper-virulent.201931191485
906280.8737Biological cost of pyocin production during the SOS response in Pseudomonas aeruginosa. LexA and two structurally related regulators, PrtR and PA0906, coordinate the Pseudomonas aeruginosa SOS response. RecA-mediated autocleavage of LexA induces the expression of a protective set of genes that increase DNA damage repair and tolerance. In contrast, RecA-mediated autocleavage of PrtR induces antimicrobial pyocin production and a program that lyses cells to release the newly synthesized pyocin. Recently, PrtR-regulated genes were shown to sensitize P. aeruginosa to quinolones, antibiotics that elicit a strong SOS response. Here, we investigated the mechanisms by which PrtR-regulated genes determine antimicrobial resistance and genotoxic stress survival. We found that induction of PrtR-regulated genes lowers resistance to clinically important antibiotics and impairs the survival of bacteria exposed to one of several genotoxic agents. Two distinct mechanisms mediated these effects. Cell lysis genes that are induced following PrtR autocleavage reduced resistance to bactericidal levels of ciprofloxacin, and production of extracellular R2 pyocin was lethal to cells that initially survived UV light treatment. Although typically resistant to R2 pyocin, P. aeruginosa becomes transiently sensitive to R2 pyocin following UV light treatment, likely because of the strong downregulation of lipopolysaccharide synthesis genes that are required for resistance to R2 pyocin. Our results demonstrate that pyocin production during the P. aeruginosa SOS response carries both expected and unexpected costs.201425022851
61090.8735Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator. Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in [Formula: see text] Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in [Formula: see text], parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence.IMPORTANCEEntamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of E. histolytica may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.202133688012
32100.8732Nitric Oxide Responsive Heavy Metal-Associated Gene AtHMAD1 Contributes to Development and Disease Resistance in Arabidopsis thaliana. Exposure of plants to different biotic and abiotic stress condition instigates significant change in the cellular redox status; resulting in the elevation of reactive nitrogen species that play signaling role in mediating defense responses. Heavy metal associated (HMA) domain containing genes are required for spatio-temporal transportation of metal ions that bind with various enzymes and co-factors within the cell. To uncover the underlying mechanisms mediated by AtHMA genes, we identified 14 Arabidopsis HMA genes that were differentially expressed in response to nitrosative stress through RNA-seq analysis. Of those 14 genes, the expression of eight HMA genes was significantly increased, whereas that of six genes was significantly reduced. We further validated the RNA-seq results through quantitative real-time PCR analysis. Gene ontology analysis revealed the involvement of these genes in biological processes such as hemostasis and transport. The majority of these nitric oxide (NO)-responsive AtHMA gene products are carrier/transport proteins. AtHMAD1 (At1g51090) showed the highest fold change to S-nitrosocystein. We therefore, further investigated its role in oxidative and nitrosative mediated stress conditions and found that AtHMAD1 has antagonistic role in shoot and root growth. Characterization of AtHMAD1 through functional genomics showed that the knock out mutant athmad1 plants were resistant to virulent Pseudomonas syringae (DC3000) and showed early induction and high transcript accumulation of pathogenesis related gene. Furthermore, inoculation of athamd1 with avirulent strain of the same bacteria showed negative regulation of R-gene mediated resistance. These results were supported by hypersensitive cell death response and cell death induced electrolyte leakage. AtHMAD1 was also observed to negatively regulate systemic acquired resistance SAR as the KO mutant showed induction of SAR marker genes. Overall, these results imply that NO-responsive AtHMA domain containing genes may play an important role in plant development and immunity.201627917181
725110.8731The Bacillus subtilis extracytoplasmic function σ factor σ(V) is induced by lysozyme and provides resistance to lysozyme. Bacteria encounter numerous environmental stresses which can delay or inhibit their growth. Many bacteria utilize alternative σ factors to regulate subsets of genes required to overcome different extracellular assaults. The largest group of these alternative σ factors are the extracytoplasmic function (ECF) σ factors. In this paper, we demonstrate that the expression of the ECF σ factor σ(V) in Bacillus subtilis is induced specifically by lysozyme but not other cell wall-damaging agents. A mutation in sigV results in increased sensitivity to lysozyme killing, suggesting that σ(V) is required for lysozyme resistance. Using reverse transcription (RT)-PCR, we show that the previously uncharacterized gene yrhL (here referred to as oatA for O-acetyltransferase) is in a four-gene operon which includes sigV and rsiV. In quantitative RT-PCR experiments, the expression of oatA is induced by lysozyme stress. Lysozyme induction of oatA is dependent upon σ(V). Overexpression of oatA in a sigV mutant restores lysozyme resistance to wild-type levels. This suggests that OatA is required for σ(V)-dependent resistance to lysozyme. We also tested the ability of lysozyme to induce the other ECF σ factors and found that only the expression of sigV is lysozyme inducible. However, we found that the other ECF σ factors contributed to lysozyme resistance. We found that sigX and sigM mutations alone had very little effect on lysozyme resistance but when combined with a sigV mutation resulted in significantly greater lysozyme sensitivity than the sigV mutation alone. This suggests that sigV, sigX, and sigM may act synergistically to control lysozyme resistance. In addition, we show that two ECF σ factor-regulated genes, dltA and pbpX, are required for lysozyme resistance. Thus, we have identified three independent mechanisms which B. subtilis utilizes to avoid killing by lysozyme.201121856855
9989120.8730Molecular Insights into Fungal Innate Immunity Using the Neurospora crassa - Pseudomonas syringae Model. Recent comparative genomics and mechanistic analyses support the existence of a fungal immune system. Fungi encode genes with features similar to non-self recognition systems in plants, animals, and bacteria. However, limited functional or mechanistic evidence exists for the surveillance-system recognition of heterologous microbes in fungi. We found that Neurospora species coexist with Pseudomonas in their natural environment. We leveraged two model organisms, Neurospora crassa and Pseudomonas syringae DC3000 (PSTDC3000) to observe immediate fungal responses to bacteria. PSTDC3000 preferentially surrounds N. crassa cells on a solid surface, causing environmental dependent growth responses, bacterial proliferation and varying fungal fitness. Specifically, the Type III secretion system (T3SS) ΔhrcC mutant of PSTDC3000 colonized N. crassa hyphae less well. To dissect initial cellular signaling events within the population of germinated asexual spores (germlings), we performed transcriptomics on N. crassa after PSTDC3000 inoculation. Upon contact with live bacteria, a subpopulation of fungal germlings initiate a response as early as ten minutes post-contact revealing transcriptional differentiation of Reactive Oxygen Species (ROS) mechanisms, trace metal warfare, cell wall remodeling dynamics, multidrug-efflux transporters, secondary metabolite synthesis, and excretion. We dissected mutants of plausible receptors, signaling pathways, and responses that N. crassa uses to detect and mount a defense against PSTDC3000 and found seven genes that influence resistant and susceptibility phenotypes of N. crassa to bacterial colonization. Mutants in genes encoding a ctr copper transporter ( tcu-1 ), ferric reductase ( fer-1 ), superoxide reductase ( sod-2 ), multidrug resistance transporter ( mdr-6 ), a secreted lysozyme-Glycoside hydrolase ( lyz ) and the Woronin body tether leashin (NCU02793, lah-1 and lah-2 ) showed a significant reduction of growth in the presence of bacteria, allowing the bacteria to fully take over the fungal mycelium faster than wildtype. In this study we provide a bacterial-fungal model system within Dikarya that allows us to begin to dissect signaling pathways of the putative fungal immune system.202539896647
583130.8728MarR family proteins sense sulfane sulfur in bacteria. Members of the multiple antibiotic resistance regulator (MarR) protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance. MarR family proteins function as repressors, and their interactions with modulators induce the expression of controlled genes. The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins. However, recently, several MarR family proteins have been reported to sense sulfane sulfur, including zero-valent sulfur, persulfide (R-SSH), and polysulfide (R-SnH, n ≥ 2). Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth. The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes. Sulfane sulfur reacts with the cysteine thiols of MarR family proteins, causing the formation of protein thiol persulfide, disulfide bonds, and other modifications. Several MarR family proteins that respond to reactive oxygen species (ROS) also sense sulfane sulfur, as both sulfane sulfur and ROS induce the formation of disulfide bonds. This review focused on MarR family proteins that sense sulfane sulfur. However, the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur, which is emerging as a modulator of gene regulation.202438948149
8194140.8727Role of the phenazine-inducing protein Pip in stress resistance of Pseudomonas chlororaphis. The triggering of antibiotic production by various environmental stress molecules can be interpreted as bacteria's response to obtain increased fitness to putative danger, whereas the opposite situation - inhibition of antibiotic production - is more complicated to understand. Phenazines enable Pseudomonas species to eliminate competitors for rhizosphere colonization and are typical virulence factors used for model studies. In the present work, we have investigated the negative effect of subinhibitory concentrations of NaCl, fusaric acid and two antibiotics on quorum-sensing-controlled phenazine production by Pseudomonas chlororaphis. The selected stress factors inhibit phenazine synthesis despite sufficient cell density. Subsequently, we have identified connections between known genes of the phenazine-inducing cascade, including PsrA (Pseudomonas sigma regulator), RpoS (alternative sigma factor), Pip (phenazine inducing protein) and PhzI/PhzR (quorum-sensing system). Under all tested conditions, overexpression of Pip or PhzR restored phenazine production while overexpression of PsrA or RpoS did not. This forced restoration of phenazine production in strains overexpressing regulatory genes pip and phzR significantly impairs growth and stress resistance; this is particularly severe with pip overexpression. We suggest a novel physiological explanation for the inhibition of phenazine virulence factors in pseudomonas species responding to toxic compounds. We propose that switching off phenazine-1-carboxamide (PCN) synthesis by attenuating pip expression would favour processes required for survival. In our model, this 'decision' point for promoting PCN production or stress resistance is located downstream of rpoS and just above pip. However, a test with the stress factor rifampicin shows no significant inhibition of Pip production, suggesting that stress factors may also target other and so far unknown protagonists of the PCN signalling cascade.201121030433
648150.8726SpoVG Is a Conserved RNA-Binding Protein That Regulates Listeria monocytogenes Lysozyme Resistance, Virulence, and Swarming Motility. In this study, we sought to characterize the targets of the abundant Listeria monocytogenes noncoding RNA Rli31, which is required for L. monocytogenes lysozyme resistance and pathogenesis. Whole-genome sequencing of lysozyme-resistant suppressor strains identified loss-of-expression mutations in the promoter of spoVG, and deletion of spoVG rescued lysozyme sensitivity and attenuation in vivo of the rli31 mutant. SpoVG was demonstrated to be an RNA-binding protein that interacted with Rli31 in vitro. The relationship between Rli31 and SpoVG is multifaceted, as both the spoVG-encoded protein and the spoVG 5′-untranslated region interacted with Rli31. In addition, we observed that spoVG-deficient bacteria were nonmotile in soft agar and suppressor mutations that restored swarming motility were identified in the gene encoding a major RNase in Gram-positive bacteria, RNase J1. Collectively, these findings suggest that SpoVG is similar to global posttranscriptional regulators, a class of RNA-binding proteins that interact with noncoding RNA, regulate genes in concert with RNases, and control pleiotropic aspects of bacterial physiology. IMPORTANCE: spoVG is widely conserved among bacteria; however, the function of this gene has remained unclear since its initial characterization in 1977. Mutation of spoVG impacts various phenotypes in Gram-positive bacteria, including methicillin resistance, capsule formation, and enzyme secretion in Staphylococcus aureus and also asymmetric cell division, hemolysin production, and sporulation in Bacillus subtilis. Here, we demonstrate that spoVG mutant strains of Listeria monocytogenes are hyper-lysozyme resistant, hypervirulent, nonmotile, and misregulate genes controlling carbon metabolism. Furthermore, we demonstrate that SpoVG is an RNA-binding protein. These findings suggest that SpoVG has a role in L. monocytogenes, and perhaps in other bacteria, as a global gene regulator. Posttranscriptional gene regulators help bacteria adapt to various environments and coordinate differing aspects of bacterial physiology. SpoVG may help the organism coordinate environmental growth and virulence to survive as a facultative pathogen.201627048798
54160.8725Strigolactones Modulate Salicylic Acid-Mediated Disease Resistance in Arabidopsis thaliana. Strigolactones are low-molecular-weight phytohormones that play several roles in plants, such as regulation of shoot branching and interactions with arbuscular mycorrhizal fungi and parasitic weeds. Recently, strigolactones have been shown to be involved in plant responses to abiotic and biotic stress conditions. Herein, we analyzed the effects of strigolactones on systemic acquired resistance induced through salicylic acid-mediated signaling. We observed that the systemic acquired resistance inducer enhanced disease resistance in strigolactone-signaling and biosynthesis-deficient mutants. However, the amount of endogenous salicylic acid and the expression levels of salicylic acid-responsive genes were lower in strigolactone signaling-deficient max2 mutants than in wildtype plants. In both the wildtype and strigolactone biosynthesis-deficient mutants, the strigolactone analog GR24 enhanced disease resistance, whereas treatment with a strigolactone biosynthesis inhibitor suppressed disease resistance in the wildtype. Before inoculation of wildtype plants with pathogenic bacteria, treatment with GR24 did not induce defense-related genes; however, salicylic acid-responsive defense genes were rapidly induced after pathogenic infection. These findings suggest that strigolactones have a priming effect on Arabidopsis thaliana by inducing salicylic acid-mediated disease resistance.202235563637
751170.8724Global transcriptomics and targeted metabolite analysis reveal the involvement of the AcrAB efflux pump in physiological functions by exporting signaling molecules in Photorhabdus laumondii. In Gram-negative bacteria, resistance-nodulation-division (RND)-type efflux pumps, particularly AcrAB-TolC, play a critical role in mediating resistance to antimicrobial agents and toxic metabolites, contributing to multidrug resistance. Photorhabdus laumondii is an entomopathogenic bacterium that has garnered significant interest due to its production of bioactive specialized metabolites with anti-inflammatory, antimicrobial, and scavenger deterrent properties. In previous work, we demonstrated that AcrAB confers self-resistance to stilbenes in P. laumondii TT01. Here, we explore the pleiotropic effects of AcrAB in this bacterium. RNA sequencing of ∆acrA compared to wild type revealed growth-phase-specific gene regulation, with stationary-phase cultures showing significant downregulation of genes involved in stilbene, fatty acid, and anthraquinone pigment biosynthesis, as well as genes related to cellular clumping and fimbrial pilin formation. Genes encoding putative LuxR regulators, type VI secretion systems, two-partner secretion systems, and contact-dependent growth inhibition systems were upregulated in ∆acrA. Additionally, exponential-phase cultures revealed reduced expression of genes related to motility in ∆acrA. The observed transcriptional changes were consistent with phenotypic assays, demonstrating that the ∆acrA mutant had altered bioluminescence and defective orange pigmentation due to disrupted anthraquinone production. These findings confirm the role of stilbenes as signaling molecules involved in gene expression, thereby shaping these phenotypes. Furthermore, we showed that AcrAB contributes to swarming and swimming motilities independently of stilbenes. Collectively, these results highlight that disrupting acrAB causes transcriptional and metabolic dysregulation in P. laumondii, likely by impeding the export of key signaling molecules such as stilbenes, which may serve as a ligand for global transcriptional regulators.IMPORTANCERecent discoveries have highlighted Photorhabdus laumondii as a promising source of novel anti-infective compounds, including non-ribosomal peptides and polyketides. One key player in the self-resistance of this bacterium to stilbene derivatives is the AcrAB-TolC complex, which is also a well-known contributor to multidrug resistance. Here, we demonstrate the pleiotropic effects of the AcrAB efflux pump in P. laumondii TT01, impacting secondary metabolite biosynthesis, motility, and bioluminescence. These effects are evident at transcriptional, metabolic, and phenotypic levels and are likely mediated by the efflux of signaling molecules such as stilbenes. These findings shed light on the multifaceted roles of efflux pumps and open avenues to better explore the complexity of resistance-nodulation-division (RND) pump-mediated signaling pathways in bacteria, thereby aiding in combating multidrug-resistant infections.202540920493
18180.8724Antivirulence effects of cell-free culture supernatant of endophytic bacteria against grapevine crown gall agent, Agrobacterium tumefaciens, and induction of defense responses in plantlets via intact bacterial cells. BACKGROUND: Crown gall disease caused by Agrobacterium tumefaciens is a very destructive affliction that affects grapevines. Endophytic bacteria have been discovered to control plant diseases via the use of several mechanisms. This research examined the potential for controlling crown gall by three endophytic bacteria that were previously isolated from healthy cultivated and wild grapevines including Pseudomonas kilonensis Ba35, Pseudomonas chlororaphis Ba47, and Serratia liquefaciens Ou55. RESULT: At various degrees, three endophytic bacteria suppressed the populations of A. tumefaciens Gh1 and greatly decreased the symptoms of crown gall. Furthermore, biofilm production and motility behaviors of A. tumefaciens Gh1were greatly inhibited by the Cell-free Culture Supernatant (CFCS) of endophytic bacteria. According to our findings, CFCS may reduce the adhesion of A. tumefaciens Gh1 cells to grapevine cv. Rashe root tissues as well as their chemotaxis motility toward the extract of the roots. When compared to the untreated control, statistical analysis showed that CFCS significantly reduced the swimming, twitching, and swarming motility of A. tumefaciens Gh1. The findings demonstrated that the endophytic bacteria effectively stimulated the production of plant defensive enzymes including superoxide dismutase (SOD), polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), and total soluble phenols at different time intervals in grapevine inoculated with A. tumefaciens Gh1. The Ba47 strain markedly increased the expression levels of defense genes associated with plant resistance. The up-regulation of PR1, PR2, VvACO1, and GAD1 genes in grapevine leaves indicates the activation of SA and JA pathways, which play a role in enhancing resistance to pathogen invasion. The results showed that treating grapevine with Ba47 increased antioxidant defense activities and defense-related gene expression, which reduced oxidative damage caused by A. tumefaciens and decreased the incidence of crown gall disease. CONCLUSION: This is the first study on how A. tumefaciens, the grapevine crown gall agent, is affected by CFCS generated by endophytic bacteria in terms of growth and virulence features. To create safer plant disease management techniques, knowledge of the biocontrol processes mediated by CFCS during microbial interactions is crucial.202438336608
8192190.8723Resisting the Heat: Bacterial Disaggregases Rescue Cells From Devastating Protein Aggregation. Bacteria as unicellular organisms are most directly exposed to changes in environmental growth conditions like temperature increase. Severe heat stress causes massive protein misfolding and aggregation resulting in loss of essential proteins. To ensure survival and rapid growth resume during recovery periods bacteria are equipped with cellular disaggregases, which solubilize and reactivate aggregated proteins. These disaggregases are members of the Hsp100/AAA+ protein family, utilizing the energy derived from ATP hydrolysis to extract misfolded proteins from aggregates via a threading activity. Here, we describe the two best characterized bacterial Hsp100/AAA+ disaggregases, ClpB and ClpG, and compare their mechanisms and regulatory modes. The widespread ClpB disaggregase requires cooperation with an Hsp70 partner chaperone, which targets ClpB to protein aggregates. Furthermore, Hsp70 activates ClpB by shifting positions of regulatory ClpB M-domains from a repressed to a derepressed state. ClpB activity remains tightly controlled during the disaggregation process and high ClpB activity states are likely restricted to initial substrate engagement. The recently identified ClpG (ClpK) disaggregase functions autonomously and its activity is primarily controlled by substrate interaction. ClpG provides enhanced heat resistance to selected bacteria including pathogens by acting as a more powerful disaggregase. This disaggregase expansion reflects an adaption of bacteria to extreme temperatures experienced during thermal based sterilization procedures applied in food industry and medicine. Genes encoding for ClpG are transmissible by horizontal transfer, allowing for rapid spreading of extreme bacterial heat resistance and posing a threat to modern food production.202134017857