Deep neural networks (DNN) have achieved unprecedented success in numerous machine learning tasks in various domains. However, the existence of adversarial examples raises our concerns in adopting ...deep learning to safety-critical applications. As a result, we have witnessed increasing interests in studying attack and defense mechanisms for DNN models on different data types, such as images, graphs and text. Thus, it is necessary to provide a systematic and comprehensive overview of the main threats of attacks and the success of corresponding countermeasures. In this survey, we review the state of the art algorithms for generating adversarial examples and the countermeasures against adversarial examples, for three most popular data types, including images, graphs and text.
ABSTRACT
Xanthomonas is a well-studied genus of bacterial plant pathogens whose members cause a variety of diseases in economically important crops worldwide. Genomic and functional studies of these ...phytopathogens have provided significant understanding of microbial-host interactions, bacterial virulence and host adaptation mechanisms including microbial ecology and epidemiology. In addition, several strains of Xanthomonas are important as producers of the extracellular polysaccharide, xanthan, used in the food and pharmaceutical industries. This polymer has also been implicated in several phases of the bacterial disease cycle. In this review, we summarise the current knowledge on the infection strategies and regulatory networks controlling virulence and adaptation mechanisms from Xanthomonas species and discuss the novel opportunities that this body of work has provided for disease control and plant health.
Here, we discuss the current knowledge surrounding regulatory networks and systems that control virulence and adaption mechanisms in Xanthomonas species. Additionally, we detail how study of these pathogens has provided novel opportunities for disease control and plant health.
Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) ...family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.
Stenotrophomonas maltophilia
is an antibiotic-resistant Gram-negative pathogen, which is associated with hospital-acquired infection. The genome encodes a protein highly related to the Ax21 protein ...of
Xanthomonas oryzae
that is implicated in interactions of this plant pathogen with rice. Here, we report on the pleiotropic nature of
ax21
mutation in
S. maltophilia
and the effects of addition of the Ax21 protein on the restoration of the wild-type phenotype. We show that loss by mutation of Ax21 leads to reduced motility, reduced biofilm formation, reduced tolerance to the antibiotic tobramycin and reduced virulence to larvae of
Galleria mellonella
, as well as alteration in the expression of specific genes associated with virulence or antibiotic resistance. Addition of the Ax21protein restored motility and the level of gene expression towards wild type. These findings are consistent with the notion that the Ax21 protein is involved in intraspecies communication, although other interpretations cannot be discounted.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The bacterial phytopathogen Xanthomonas campestris pv. campestris (Xcc) relies on the hrp (hypersensitive response and pathogenicity) genes to cause disease and induce hypersensitive response (HR). ...The hrp genes of bacterial phytopathogens are divided into two groups. Xcc hrp genes belong to group II. It has long been known that the group II hrp genes are activated by an AraC‐type transcriptional regulator whose expression is controlled by a two‐component system (TCS) response regulator (named HrpG in Xcc). However, no cognate sensor kinase has yet been identified. Here, we present evidence showing that the Xcc open‐reading frame XC_3670 encodes a TCS sensor kinase (named HpaS). Mutation of hpaS almost completely abolished the HR induction and virulence. Bacterial two‐hybrid and protein pull‐down assays revealed that HpaS physically interacted with HrpG. Phos‐tag™ SDS‐PAGE analysis showed that mutation in hpaS reduced markedly the phosphorylation of HrpG in vivo. These data suggest that HpaS and HrpG are most likely to form a TCS. We also showed that XC_3669 (named hpaR2), which is adjacent to hpaS and encodes a putative TCS response regulator, is required for full virulence but not HR induction. HpaR2 also physically interacted with HpaS, suggesting that HpaS may also form another TCS with HpaR2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical S. maltophilia isolate K279a indicates that it encodes a ...diffusible signal factor (DSF)-dependent cell-cell signaling mechanism that is highly similar to the system previously described in phytopathogens from the genera Xanthomonas and Xylella. Our objective was to study the function of DSF signaling in the clinical strain S. maltophilia K279a using genetic and functional genomic analyses.
We compared the wild-type strain with a mutant deficient in the rpfF (regulation of pathogenicity factors) gene that is essential for the synthesis of DSF. The effects of disruption of DSF signaling were pleiotropic with an impact on virulence, biofilm formation and pathogenesis. The phenotypic effects of rpfF mutation in S. maltophilia could be reversed by addition of exogenous DSF. Taken together, we demonstrate that DSF signaling regulates factors contributing to virulence, biofilm formation and motility of this important opportunistic pathogen.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
All known riboswitches use their aptamer to senese one metabolite signal and their expression platform to regulate gene expression. Here, we characterize a SAM-I riboswitch (SAM-I
) from the ...Xanthomonas campestris that regulates methionine synthesis via the met operon. In vitro and in vivo experiments show that SAM-I
controls the met operon primarily at the translational level in response to cellular S-adenosylmethionine (SAM) levels. Biochemical and genetic data demonstrate that SAM-I
expression platform not only can repress gene expression in response to SAM binding to SAM-I
aptamer but also can sense and bind uncharged initiator Met tRNA, resulting in the sequestering of the anti-Shine-Dalgarno (SD) sequence and freeing the SD for translation initiation. These findings identify a SAM-I riboswitch with a dual functioning expression platform that regulates methionine synthesis through a previously unrecognized mechanism and discover a natural tRNA-sensing RNA element. This SAM-I riboswitch appears to be highly conserved in Xanthomonas species.
Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in crucifers. Our previous findings revealed that Xcc can degrade 4‐hydroxybenzoic acid (4‐HBA) via the β‐ketoadipate ...pathway. This present study expands on this knowledge in several ways. First, we show that infective Xcc cells induce in situ biosynthesis of 4‐HBA in host plants, and Xcc can efficiently degrade 4‐HBA via the pobA/pobR locus, which encodes a 4‐hydroxybenzoate hydroxylase and an AraC‐family transcription factor respectively. Next, the transcription of pobA is specifically induced by 4‐HBA and is positively regulated by PobR, which is constitutively expressed in Xcc. 4‐HBA directly binds to PobR dimers, resulting in activation of pobA expression. Point mutation and subsequent isothermal titration calorimetry and size exclusion chromatography analysis identified nine key conserved residues required for 4‐HBA binding and/or dimerization of PobR. Furthermore, overlapping promoters harboring fully overlapping −35 elements were identified between the divergently transcribed pobA and pobR. The 4‐HBA/PobR dimer complex specifically binds to a 25‐bp site, which encompasses the −35 elements shared by the overlapping promoters. Finally, GUS histochemical staining and subsequent quantitative assay showed that both pobA and pobR genes are transcribed during Xcc infection of Chinese radish, and the strain ΔpobR exhibited compromised virulence in Chinese radish. These findings suggest that the ability of Xcc to survive the 4‐HBA stress might be important for its successful colonization of host plants.
The phytopathogen Xanthomonas campestris pv. campestris (Xcc) can degrade 4‐hydroxybenzoic acid(4‐HBA) via the pobA/pobR locus. This study investigated the molecular mechanisms underlying 4‐HBA binding to PobR to induce pobA expression and the roles of this locus in Xcc infection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on the type III secretion system (T3SS). Proteins of the Xcc T3SS are ...encoded by hrp (hypersensitive response and pathogenicity) genes and whose expression is mainly controlled by the regulators HrpG and HrpX. Here, we describe the identification and characterization of a previously unknown regulatory protein (named HpaP), which plays important role in hrp gene expression and virulence in Xcc. Clean deletion of hpaP demonstrated reduced virulence and HR (hypersensitive response) induction of Xcc and alterations in cell motility and stress tolerance. Global transcriptome analyses revealed that most hrp genes were down regulated in the hpaP mutant, suggesting HpaP positively regulates hrp genes. GUS activity assays implied that HpaP regulates the expression of hrp genes via controlling the expression of hrpX. Biochemical analyses revealed that HpaP protein had both ATPase and phosphatase activity. While further site‐directed mutagenesis of conserved residues in the PTP loop (a protein tyrosine phosphatase signature) of HpaP resulted in the loss of both phosphatase activity and regulatory activity in virulence and HR. Taken together, the findings identify a new regulatory protein that controls hrp gene expression and virulence in Xcc.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Bacteria harbour several abundant small DNA‐binding proteins known as nucleoid‐associated proteins (NAPs) that contribute to the structure of the bacterial nucleoid as well as to gene regulation. ...Although the function of NAPs as global transcriptional regulators has been comprehensively studied in the model organism Escherichia coli, their regulatory functions in other bacteria remain relatively poorly understood. Xanthomonas campestris pv. campestris (Xcc) is a gram‐negative bacterium that causes black rot disease in almost all members of the crucifer family. In previous work, we demonstrated that a Fis homologue protein, which we named Fis‐like protein (Flp), contributes to the regulation of virulence, type III secretion, and a series of other phenotypes in Xcc. Here we have examined the role of XC_1355, which is predicted to encode a DNA‐binding protein belonging to the HU family herein named HU‐like protein (Hlp). We show that mutation of XC_1355 in Xcc reduces the virulence, extracellular polysaccharide production, and cell motility, but has no effect on the production of extracellular enzymes and induction of the hypersensitive response. These data together with transcriptome analysis indicate that hlp is a previously uncharacterized gene involved in virulence that has partially overlapping and complementary functions with flp in Xcc, although the two regulators have opposite effects on the expression of genes involved in type III secretion. The findings add to our understanding of the complex regulatory pathways that act to regulate virulence in Xcc.
A previously uncharacterized protein, Hlp, is involved in virulence and has opposite effects on the expression of type III secretion proteins compared with Flp.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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