Many pathogenic bacteria use cell-cell signaling systems involving the synthesis and perception of diffusible signal molecules to control virulence as a response to cell density or confinement to ...niches. Bacteria produce signals of diverse structural classes. Signal molecules of the diffusible signal factor (DSF) family are cis-2-unsaturated fatty acids. The paradigm is cis-11-methyl-2-dodecenoic acid from Xanthomonas campestris pv. campestris (Xcc), which controls virulence in this plant pathogen. Although DSF synthesis was thought to be restricted to the xanthomonads, it is now known that structurally related molecules are produced by the unrelated bacteria Burkholderia cenocepacia and Pseudomonas aeruginosa. Furthermore, signaling involving these DSF family members contributes to bacterial virulence, formation of biofilms and antibiotic tolerance in these important human pathogens. Here we review the recent advances in understanding DSF signaling and its regulatory role in different bacteria. These advances include the description of the pathway/mechanism of DSF biosynthesis, identification of novel DSF synthases and new members of the DSF family, the demonstration of a diversity of DSF sensors to include proteins with a Per-Arnt-Sim (PAS) domain and the description of some of the signal transduction mechanisms that impinge on virulence factor expression. In addition, we address the role of DSF family signals in interspecies signaling that modulates the behavior of other microorganisms. Finally, we consider a number of recently reported approaches for the control of bacterial virulence through the modulation of DSF signaling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BIOMERIT Research Centre, Department of Microbiology, BioSciences Institute, National University of Ireland, Cork, Ireland
Correspondence Robert P. Ryan r.ryan{at}ucc.ie
Many bacteria use cell–cell ...communication mediated by diffusible signal molecules to monitor their population density or confinement to niches and to modulate their behaviour in response to these aspects of their environment. Work on signalling systems within individual species has formed a platform for studies of interspecies interactions that can occur within polymicrobial communities in nature. In addition to signalling between organisms that synthesize the same or related signal molecules, it is becoming evident that bacteria can sense signal molecules that they do not synthesize, thereby eavesdropping on signalling by other organisms in their immediate environment. Furthermore, molecules such as antibiotics that are considered not to be signals for the producing species can have effects on gene expression in other bacteria that indicate a signalling function. Interspecies signalling can lead to alteration in factors contributing to the virulence or persistence of bacterial pathogens as well as influencing the development of beneficial microbial communities. Here we review our current understanding of interspecies signalling in bacteria and the signals involved, what is known of the underlying signal transduction mechanisms and their influences on bacterial behaviour.
Abbreviations: AI-2, -3, autoinducer-2, -3; AIP, autoinducing peptide; DF, diffusible factor; DKP, diketopiperazine; DPD, 4,5-dihydroxy-2,3-pentanedione; DSF, diffusible signal factor; N -AHL, N -acylhomoserine lactone
Xanthomonas is a large genus of Gram-negative bacteria that cause disease in hundreds of plant hosts, including many economically important crops. Pathogenic species and pathovars within species show ...a high degree of host plant specificity and many exhibit tissue specificity, invading either the vascular system or the mesophyll tissue of the host. In this Review, we discuss the insights that functional and comparative genomic studies are providing into the adaptation of this group of bacteria to exploit the extraordinary diversity of plant hosts and different host tissues.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The genus Stenotrophomonas comprises at least eight species. These bacteria are found throughout the environment, particularly in close association with plants. Strains of the most predominant ...species, Stenotrophomonas maltophilia, have an extraordinary range of activities that include beneficial effects for plant growth and health, the breakdown of natural and man-made pollutants that are central to bioremediation and phytoremediation strategies and the production of biomolecules of economic value, as well as detrimental effects, such as multidrug resistance, in human pathogenic strains. Here, we discuss the versatility of the bacteria in the genus Stenotrophomonas and the insight that comparative genomic analysis of clinical and endophytic isolates of S. maltophilia has brought to our understanding of the adaptation of this genus to various niches.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cyclic di-GMP was the first cyclic dinucleotide second messenger described, presaging the discovery of additional cyclic dinucleotide messengers in bacteria and eukaryotes. The GGDEF diguanylate ...cyclase (DGC) and EAL and HD-GYP phosphodiesterase (PDE) domains conduct the turnover of cyclic di-GMP. These three unrelated domains belong to superfamilies that exhibit significant variations in function, and they include both enzymatically active and inactive members, with a subset involved in synthesis and degradation of other cyclic dinucleotides. Here, we summarize current knowledge of sequence and structural variations that underpin the functional diversification of cyclic di-GMP turnover proteins. Moreover, we highlight that superfamily diversification is not restricted to cyclic di-GMP signaling domains, as particular DHH/DHHA1 domain and HD domain proteins have been shown to act as cyclic di-AMP phosphodiesterases. We conclude with a consideration of the current limitations that such diversity of action places on bioinformatic prediction of the roles of GGDEF, EAL, and HD-GYP domain proteins.
Many pathogenic bacteria use cell–cell signaling to regulate the expression of factors contributing to virulence. Bacteria produce signals of diverse structural classes. The signal molecule known as ...diffusible signal factor (DSF) is a cis -unsaturated fatty acid that was first described in the plant pathogen Xanthomonas campestris . Recent work has shown that structurally related molecules produced by the unrelated bacteria Burkholderia cenocepacia and Pseudomonas aeruginosa regulate virulence, biofilm formation and antibiotic tolerance in these important human pathogens. Furthermore, DSF family signals have been shown to be involved in interspecies signaling that modulates bacterial behavior. An understanding of these diverse signaling mechanisms could suggest strategies for interference, with consequences for disease control.
The rpf gene cluster of Xanthomonas campestris pathovar campestris (Xcc) is required for the pathogenesis of this bacterium to plants. Several rpf genes are involved in the coordinate positive ...regulation of the production of virulence factors mediated by the small diffusible molecule DSF (for diffusible signal factor). RpfF directs the synthesis of DSF, and a two-component sensory transduction system comprising RpfC and RpfG has been implicated in the perception of the DSF signal and signal transduction. In L medium, rpfF, rpfG, rpfC, and rpfGHC mutants grew as matrix-enclosed aggregates, whereas the wild type grew in a dispersed planktonic fashion. Synthesis of the extracellular polysaccharide xanthan was required for aggregate formation. Addition of DSF triggered dispersion of the aggregates formed by the rpfF strain, but not those of rpf strains defective in DSF signal transduction. An extracellular enzyme from Xcc whose synthesis was positively controlled by the DSF/rpf system could disperse the aggregates produced by all rpf strains. The enzyme was identified as the single endo-β-1,4-mannanase encoded by the Xcc genome. This enzyme had no detectable activity against soluble xanthan. The endo-β-1,4-mannanase was required for the full virulence of Xcc to plants. On the basis of this model system, we propose that one role of the β-mannanase during disease is to promote transitions from an aggregated or biofilm lifestyle to a planktonic lifestyle in response to the DSF signal.
Cyclic di-GMP is a second messenger found in almost all eubacteria that acts to regulate a wide range of functions including developmental transitions, adhesion and biofilm formation. Cyclic di-GMP ...is synthesised from two GTP molecules by diguanylate cyclases that have a GGDEF domain and is degraded by phosphodiesterases with either an EAL or an HD-GYP domain. Proteins with these domains often contain additional signal input domains, suggesting that their enzymatic activity may be modulated as a response to different environmental or cellular cues. Cyclic di-GMP exerts a regulatory action through binding to diverse receptors that include a small protein domain called PilZ, enzymatically inactive GGDEF, EAL or HD-GYP domains, transcription factors and riboswitches. In many bacteria, high cellular levels of cyclic di-GMP are associated with a sessile, biofilm lifestyle, whereas low levels of the nucleotide promote motility and virulence factor synthesis in pathogens. Elucidation of the roles of cyclic di-GMP signalling in biofilm formation has suggested strategies whereby modulation of the levels of the nucleotide or interference with signalling pathways may lead to inhibition of biofilm formation or promotion of biofilm dispersal. In this review we consider these approaches for the control of biofilm formation, beginning with an overview of cyclic di-GMP signalling and the different ways that it can act in regulation of biofilm dynamics.
Molecules exuded by plant roots are thought to act as signals to influence the ability of microbial strains to colonize the roots and to survive in the rhizosphere. Differential bacterial responses ...to signals from different plant species may mediate the selection of specific rhizosphere populations. Very little, however, is known about the effects of plant exudates on patterns of bacterial gene expression. Here, we have tested the concept that plant root exudates modulate expression of bacterial genes involved in establishing microbe-plant interactions. We have examined the influence on the Pseudomonas aeruginosa PA01 transcriptome of exudates from two varieties of sugarbeet that select for genetically distinct pseudomonad populations in the rhizosphere. The response to the two exudates showed only a partial overlap; the majority of those genes with altered expression was regulated in response to only one of the two exudates. Genes with altered expression included those with functions previously implicated in microbe-plant interactions, such as aspects of metabolism, chemotaxis and type III secretion, and a subset with putative or unknown function. Use of a panel of mutants with targeted disruptions allowed us to identify previously uncharacterized genes with roles in the competitive ability of P. aeruginosa in the rhizosphere within this subset. No genes with host-specific effects were identified. Homologues of the genes identified occur in the genomes of both beneficial and pathogenic root-associated bacteria, suggesting that this strategy may help to elucidate molecular interactions that are important for biocontrol, plant growth promotion, and plant pathogenesis.
Summary
Burkholderia cenocepacia is an opportunistic respiratory pathogen that can cause severe infections in immune‐compromised individuals and is associated with poor prognosis for patients ...suffering from cystic fibrosis. The second messenger cyclic diguanosine monophosphate (c‐di‐GMP) has been shown to control a wide range of functions in bacteria, but little is known about these regulatory mechanisms in B. cenocepacia. Here we investigated the role that c‐di‐GMP plays in the regulation of biofilm formation and virulence in B. cenocepacia. Elevated intracellular levels of c‐di‐GMP promoted wrinkly colony, pellicle and biofilm formation in B. cenocepacia. A screen for transposon mutants unable to respond to elevated levels of c‐di‐GMP led to the identification of the mutant bcam1349 that did not display increased biofilm and pellicle formation with excessive c‐di‐GMP levels, and displayed a biofilm defect with physiological c‐di‐GMP levels. The bcam1349 gene is predicted to encode a transcriptional regulator of the CRP/FNR superfamily. Analyses of purified Bcam1349 protein and truncations demonstrated that it binds c‐di‐GMP in vitro. The Bcam1349 protein was shown to regulate the production of a number of components, including cellulose and fimbriae. It was demonstrated that the Bcam1349 protein binds to the promoter region of the cellulose synthase genes, and that this binding is enhanced by the presence of c‐di‐GMP. The bcam1349 mutant showed reduced virulence in a Galleria mellonella wax moth larvae infection model. Taken together, these findings suggest that the Bcam1349 protein is a transcriptional regulator that binds c‐di‐GMP and regulates biofilm formation and virulence in B. cenocepacia in response to the level of c‐di‐GMP.
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