scholarly journals Elucidation of the Pathogenicity-Associated Regulatory Network in Xanthomonas oryzae pv. oryzae

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Dehong Zheng ◽  
Huihui Wang ◽  
Hao Zhong ◽  
Wenli Ke ◽  
Huifeng Hu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cross Talk ◽  
Regulatory Network ◽  
Pathogenic Bacteria ◽  
Infection Process ◽  
Xanthomonas Oryzae ◽  
Global Network ◽  
Dynamic Regulation ◽  
Content Type ◽  
Signal Transduction Systems

ABSTRACT Xanthomonas is a notorious plant pathogen causing serious diseases in hundreds of plant hosts. Xanthomonas species are equipped with an array of signal transduction systems that regulate gene expression to survive in various harsh environments and successfully infect hosts. Although certain pathogenicity-associated regulators have been functionally characterized, signal transduction systems always function as a regulatory network which remains to be elucidated in Xanthomonas. This study used a systematic approach to characterize all identified pathogenicity-associated regulators in Xanthomonas oryzae pv. oryzae (Xoo), including a transcriptional regulator with unknown function, and their interactive regulatory network. RNA sequencing was used in elucidating the patterns of the 10 pathogenicity-associated regulators identified. Results revealed that each pathogenicity-associated regulator has cross talk with others and all these regulators function as a regulatory network, with VemR and PXO_RS20790 being the master pathogenicity-associated regulators and HrpX being the final executant. Moreover, regulome analysis showed that numerous genes other than genes in pathogenicity islands are finely regulated within the regulatory network. Given that most of the pathogenicity-associated regulators are conserved in Xanthomonadales, our findings suggest a global network of gene regulation in this evolutionarily conserved pathogen. In conclusion, our study provides essential basic information about the regulatory network in Xoo, suggesting that this complicated regulatory network is one of the reasons for the robustness and fitness of Xanthomonas spp. IMPORTANCE The host plant infection process of pathogenic bacteria is a coordinating cellular behavior, which requires dynamic regulation at several levels in response to variations in host plants or fluctuations in the external environment. As one of the most important genera of plant-pathogenic bacteria, Xanthomonas has been studied as a model. Although certain pathogenicity-associated regulators have been functionally characterized, interactions among them remain to be elucidated. This study systematically characterized pathogenicity-associated regulators in Xoo and revealed that cross talk exists among pathogenicity-associated regulators and function as a regulatory network in which a hierarchy exists among the regulators. Our study elucidated the landscape of the pathogenicity-associated regulatory network in Xanthomonas, promoting understanding of the infection process of pathogenic bacteria.

scholarly journals Quinazoline-Based Antivirulence Compounds Selectively Target Salmonella PhoP/PhoQ Signal Transduction System

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
María Ayelén Carabajal ◽  
Christopher R. M. Asquith ◽  
Tuomo Laitinen ◽  
Graham J. Tizzard ◽  
Lucía Yim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Catalytic Domain ◽  
Kinase Inhibitor ◽  
Adaptive Responses ◽  
Antibacterial Compounds ◽  
Content Type ◽  
Two Component ◽  
Serovar Typhimurium

ABSTRACT The rapid emergence of multidrug resistance among bacterial pathogens has become a significant challenge to human health in our century. Therefore, development of next-generation antibacterial compounds is an urgent need. Two-component signal transduction systems (TCS) are stimulus-response coupling devices that allow bacteria to sense and elaborate adaptive responses to changing environmental conditions, including the challenges that pathogenic bacteria face inside the host. The differential presence of TCS, present in bacteria but absent in the animal kingdom, makes them attractive targets in the search for new antibacterial compounds. In Salmonella enterica, the PhoP/PhoQ two-component system controls the expression of crucial phenotypes that define the ability of the pathogen to establish infection in the host. We now report the screening of 686 compounds from a GlaxoSmithKline published kinase inhibitor set in a high-throughput whole-cell assay that targets Salmonella enterica serovar Typhimurium PhoP/PhoQ. We identified a series of quinazoline compounds that showed selective and potent downregulation of PhoP/PhoQ-activated genes and define structural attributes required for their efficacy. We demonstrate that their bioactivity is due to repression of the PhoQ sensor autokinase activity mediated by interaction with its catalytic domain, acting as competitive inhibitors of ATP binding. While noncytotoxic, the hit molecules exhibit antivirulence effect by blockage of S. Typhimurium intramacrophage replication. Together, these features make these quinazoline compounds stand out as exciting leads to develop a therapeutic intervention to fight salmonellosis.

scholarly journals Two-Component Signal Transduction Systems in the Human Pathogen Streptococcus agalactiae

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Lamar Thomas ◽  
Laura Cook
Keyword(s):  
Signal Transduction ◽  
Streptococcus Agalactiae ◽  
Metabolic Regulation ◽  
Invasive Infection ◽  
Older Individuals ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Group B ◽  
Signal Transduction Systems

ABSTRACT Streptococcus agalactiae (group B Streptococcus [GBS]) is an important cause of invasive infection in newborns, maternal women, and older individuals with underlying chronic illnesses. GBS has many mechanisms to adapt and survive in its host, and these mechanisms are often controlled via two-component signal transduction systems. In GBS, more than 20 distinct two-component systems (TCSs) have been classified to date, consisting of canonical TCSs as well as orphan and atypical sensors and regulators. These signal transducing systems are necessary for metabolic regulation, resistance to antibiotics and antimicrobials, pathogenesis, and adhesion to the mucosal surfaces to colonize the host. This minireview discusses the structures of these TCSs in GBS as well as how selected systems regulate essential cellular processes such as survival and colonization. GBS contains almost double the number of TCSs compared to the closely related Streptococcus pyogenes and Streptococcus pneumoniae, and while research on GBS TCSs has been increasing in recent years, no comprehensive reviews of these TCSs exist, making this review especially relevant.

scholarly journals Identification of Proteins Likely To Be Involved in Morphogenesis, Cell Division, and Signal Transduction in Planctomycetes by Comparative Genomics

2012 ◽  
Vol 194 (23) ◽  
pp. 6419-6430 ◽  
Author(s):  
Christian Jogler ◽  
Jost Waldmann ◽  
Xiaoluo Huang ◽  
Mareike Jogler ◽  
Frank Oliver Glöckner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Division ◽  
Model Organisms ◽  
Genetic Studies ◽  
Content Type ◽  
Life Styles ◽  
Membrane Bound ◽  
Guilt By Association ◽  
Complex Signaling ◽  
Signal Transduction Systems

ABSTRACTMembers of thePlanctomycetesclade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits ofPlanctomycetesremain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined thePlanctomycetescore genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a “guilt-by-association” approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in thePlanctomycetesakin to that observed for bacteria with complex life-styles, such asMyxococcus xanthus.

scholarly journals The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation

2017 ◽  
Vol 199 (18) ◽  
Author(s):  
Jennifer K. Teschler ◽  
Andrew T. Cheng ◽  
Fitnat H. Yildiz
Keyword(s):  
Signal Transduction ◽  
Vibrio Cholerae ◽  
Histidine Kinase ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Response Regulator ◽  
Systematic Analysis ◽  
Content Type ◽  
Two Component ◽  
Two Component Signal Transduction

ABSTRACT Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in V. cholerae. vxrB is part of a 5-gene operon, which contains the cognate HK vxrA and three genes of unknown function. Strains carrying ΔvxrA and ΔvxrB mutations are deficient in biofilm formation, while the ΔvxrC mutation enhances biofilm formation. The overexpression of VxrB led to a decrease in motility. We also observed a small but reproducible effect of the absence of VxrB on the levels of cyclic di-GMP (c-di-GMP). Our work reveals a new function for the Vxr TCS as a regulator of biofilm formation and suggests that this regulation may act through key biofilm regulators and the modulation of cellular c-di-GMP levels. IMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, providing protection from environmental stresses and contributing to the transmission of V. cholerae to the human host. V. cholerae can utilize two-component systems (TCS), composed of a histidine kinase (HK) and a response regulator (RR), to regulate biofilm formation in response to external cues. We performed a systematic analysis of V. cholerae RRs and identified a new regulator of biofilm formation, VxrB. We demonstrated that the VxrAB TCS is essential for robust biofilm formation and that this system may regulate biofilm formation via its regulation of key biofilm regulators and cyclic di-GMP levels. This research furthers our understanding of the role that TCSs play in the regulation of V. cholerae biofilm formation.

scholarly journals Ankyrin-Like Protein AnkB Interacts with CatB, Affects Catalase Activity, and Enhances Resistance ofXanthomonas oryzaepv. oryzae andXanthomonas oryzaepv. oryzicola to Phenazine-1-Carboxylic Acid

2017 ◽  
Vol 84 (4) ◽  
Author(s):  
Xiayan Pan ◽  
Shu Xu ◽  
Jian Wu ◽  
Yabing Duan ◽  
Zhitian Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Carboxylic Acid ◽  
Catalase Activity ◽  
Pathogenic Bacteria ◽  
Adaptor Protein ◽  
Bacterial Biofilm ◽  
Xanthomonas Oryzae ◽  
Content Type ◽  
Plant Pathogenic Bacteria ◽  
Ankyrin Protein

ABSTRACTXanthomonas oryzaepv. oryzae, which causes rice bacterial leaf blight, andXanthomonas oryzaepv. oryzicola, which causes rice bacterial leaf streak, are important plant-pathogenic bacteria. A member of the adaptor protein family, ankyrin protein, has been investigated largely in humans but rarely in plant-pathogenic bacteria. In this study, a novel ankyrin-like protein, AnkB, was identified inX. oryzaepv. oryzae andX. oryzaepv. oryzicola. The expression ofankBwas significantly upregulated when these bacteria were treated with phenazine-1-carboxylic acid (PCA).ankBis located 58 bp downstream of the genecatB(which encodes a catalase) in both bacteria, and the gene expression ofcatBand catalase activity were reduced followingankBdeletion inX. oryzaepv. oryzae andX. oryzaepv. oryzicola. Furthermore, we demonstrated that AnkB directly interacts with CatB by glutathioneS-transferase (GST) pulldown assays. Deletion ofankBincreased the sensitivity ofX. oryzaepv. oryzae andX. oryzaepv. oryzicola to H2O2and PCA, decreased bacterial biofilm formation, swimming ability, and exopolysaccharide (EPS) production, and also reduced virulence on rice. Together our results indicate that the ankyrin-like protein AnkB has important and conserved roles in antioxidant systems and pathogenicity inX. oryzaepv. oryzae andX. oryzaepv. oryzicola.IMPORTANCEThis study demonstrates that the ankyrin protein AnkB directly interacts with catalase CatB inXanthomonas oryzaepv. oryzae andXanthomonas oryzaepv. oryzicola. Ankyrin protein AnkB can affect the gene expression ofcatB, catalase activity, and sensitivity to H2O2. InXanthomonasspp., the locations of genesankBandcatBand the amino acid sequence of AnkB are highly conserved. It is suggested that in prokaryotes, AnkB plays a conserved role in the defense against oxidative stress.

scholarly journals Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1209
Author(s):  
Emma Piattelli ◽  
Johann Peltier ◽  
Olga Soutourina
Keyword(s):  
Signal Transduction ◽  
Regulatory Networks ◽  
Pathogenic Bacteria ◽  
Resistant Bacteria ◽  
Human Pathogens ◽  
Environmental Threats ◽  
Regulatory Rnas ◽  
Sense And Respond ◽  
The Impact ◽  
Signal Transduction Systems

The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.

scholarly journals Pathogenicity Island Cross Talk Mediated by Recombination Directionality Factors Facilitates Excision from the Chromosome

2015 ◽  
Vol 198 (5) ◽  
pp. 766-776 ◽  
Author(s):  
Megan R. Carpenter ◽  
Sharon Rozovsky ◽  
E. Fidelma Boyd
Keyword(s):  
Cross Talk ◽  
Pathogenic Bacteria ◽  
Pathogenicity Island ◽  
Transcriptional Regulators ◽  
Diverse Range ◽  
Content Type ◽  
Genetic Elements ◽  
Complex Interactions ◽  
Attachment Sites ◽  
Absolute Requirement

ABSTRACTPathogenicity islands (PAIs) are mobile integrated genetic elements (MIGEs) that contain a diverse range of virulence factors and are essential in the evolution of pathogenic bacteria. PAIs are widespread among bacteria and integrate into the host genome, commonly at a tRNA locus, via integrase-mediated site-specific recombination. The excision of PAIs is the first step in the horizontal transfer of these elements and is not well understood. In this study, we examined the role of recombination directionality factors (RDFs) and their relationship with integrases in the excision of two PAIs essential forVibrio choleraehost colonization:Vibriopathogenicity island 1 (VPI-1) and VPI-2. VPI-1 does not contain an RDF, which allowed us to answer the question of whether RDFs are an absolute requirement for excision. We found that an RDF was required for efficient excision of VPI-2 but not VPI-1 and that RDFs can induce excision of both islands. Expression data revealed that the RDFs act as transcriptional repressors to both VPI-1- and VPI-2-encoded integrases. We demonstrated that the RDFsVibrioexcision factor A (VefA) and VefB bind at the attachment sites (overlapping theintpromoter region) of VPI-1 and VPI-2, thus supporting this mode of integrase repression. In addition,V. choleraeRDFs are promiscuous due to their dual functions of promoting excision of both VPI-1 and VPI-2 and acting as negative transcriptional regulators of the integrases. This is the first demonstration of cross talk between PAIs mediated via RDFs which reveals the complex interactions that occur between separately acquired MIGEs.IMPORTANCEDeciphering the mechanisms of pathogenicity island excision is necessary for understanding the evolution and spread of these elements to their nonpathogenic counterparts. Such mechanistic insight would assist in predicting the mobility of uncharacterized genetic elements. This study identified extensive RDF-mediated cross talk between two nonhomologous VPIs and demonstrated the dual functionality of RDF proteins: (i) inducing PAI excision and (ii) acting as transcriptional regulators. Findings from this study may be implicated in determining the mobilome contribution of other bacteria with multiple MIGEs.

scholarly journals The ChrSA and HrrSA Two-Component Systems Are Required for Transcriptional Regulation of thehemAPromoter in Corynebacterium diphtheriae

2016 ◽  
Vol 198 (18) ◽  
pp. 2419-2430 ◽  
Author(s):  
Jonathan M. Burgos ◽  
Michael P. Schmitt
Keyword(s):  
Signal Transduction ◽  
Kinase Activity ◽  
Content Type ◽  
Component Systems ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Two Component Systems ◽  
Signal Transduction Systems

ABSTRACTCorynebacterium diphtheriaeutilizes heme and hemoglobin (Hb) as iron sources for growth in low-iron environments. InC. diphtheriae, the two-component signal transduction systems (TCSs) ChrSA and HrrSA are responsive to Hb levels and regulate the transcription of promoters forhmuO,hrtAB, andhemA. ChrSA and HrrSA activate transcription at thehmuOpromoter and repress transcription athemAin an Hb-dependent manner. In this study, we show that HrrSA is the predominant repressor athemAand that its activity results in transcriptional repression in the presence and absence of Hb, whereas repression ofhemAby ChrSA is primarily responsive to Hb. DNA binding studies showed that both ChrA and HrrA bind to thehemApromoter region at virtually identical sequences. ChrA binding was enhanced by phosphorylation, while binding to DNA by HrrA was independent of its phosphorylation state. ChrA and HrrA are phosphorylatedin vitroby the sensor kinase ChrS, whereas no kinase activity was observed with HrrSin vitro. Phosphorylated ChrA was not observedin vivo, even in the presence of Hb, which is likely due to the instability of the phosphate moiety on ChrA. However, phosphorylation of HrrA was observedin vivoregardless of the presence of the Hb inducer, and genetic analysis indicates that ChrS is responsible for most of the phosphorylation of HrrAin vivo. Phosphorylation studies strongly suggest that HrrS functions primarily as a phosphatase and has only minimal kinase activity. These findings collectively show a complex mechanism of regulation at thehemApromoter, where both two-component systems act in concert to optimize expression of heme biosynthetic enzymes.IMPORTANCEUnderstanding the mechanism by which two-component signal transduction systems function to respond to environmental stimuli is critical to the study of bacterial pathogenesis. The current study expands on the previous analyses of the ChrSA and HrrSA TCSs in the human pathogenC. diphtheriae. The findings here underscore the complex interactions between the ChrSA and HrrSA systems in the regulation of thehemApromoter and demonstrate how the two systems complement one another to refine and control transcription in the presence and absence of Hb.

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