The Ax21 protein is a cell-cell signal that regulates virulence in the nosocomial pathogen Stenotrophomonas maltophilia.
Ontology highlight
ABSTRACT:
SUBMITTER: McCarthy Y
PROVIDER: S-EPMC3209228 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Publications
The Ax21 protein is a cell-cell signal that regulates virulence in the nosocomial pathogen Stenotrophomonas maltophilia.
McCarthy Yvonne Y Dow J Maxwell JM Ryan Robert P RP
Journal of bacteriology 20110909 22
Stenotrophomonas maltophilia encodes proteins related to the Rax proteins of Xanthomonas oryzae, which are required for the synthesis and secretion of the Ax21 protein. Here we show that Ax21 acts as a cell-cell signal to regulate a diverse range of functions, including virulence, in this nosocomial pathogen. ...[more]
Similar Datasets
Project description:c-di-GMP is a cellular second messenger that regulates diverse bacterial processes, including swimming, biofilm formation and virulence. However, in Stenotrophomonas maltophilia, a nosocomial pathogen that frequently infects immunodeficient or immunoincompetent patients, the regulatory function of c-di-GMP remains unclear. Here we show that BsmR is a negative regulator of biofilm development that degrades c-di-GMP through its EAL domain. Increasing BsmR expression resulted in significant increase in bacterial swimming and decrease in cell aggregation. BsmR regulates the expression of at least 349 genes. Among them, 34 involved in flagellar assembly and a flagellar-assembly-related transcription factor (fsnR) are positively regulated. Although BsmR is a response regulator of the two-component signaling system, its role in biofilm formation depends on the expression level of its respective gene (bsmR), not on the protein's phosphorylation level. A transcription factor, BsmT, whose coding gene is located in the same tetra-cistronic operon as bsmR, was shown to directly bind to the promoter region of the operon and, through a positive regulatory loop, modulate bsmR transcription. Thus, our results revealed that the c-di-GMP signaling pathway controls biofilm formation and swimming in S. maltophilia, suggesting c-di-GMP signaling as a target in the development of novel antibacterial agents to resist this pathogen.
| S-EPMC5498567 | biostudies-literature
Project description:Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.
| S-EPMC3255966 | biostudies-literature
Project description:Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins-antibiotics commonly used to treat S. maltophilia infections-have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study.
| S-EPMC4485184 | biostudies-literature
Project description:Stenotrophomonas maltophilia is an emerging nosocomial pathogen. In many bacteria iron availability regulates, through the Fur system, not only iron homeostasis but also virulence. The aim of this work was to assess the role of iron on S. maltophilia biofilm formation, EPS production, oxidative stress response, OMPs regulation, quorum sensing (QS), and virulence. Studies were done on K279a and its isogenic fur mutant F60 cultured in the presence or absence of dipyridyl. This is the first report of spontaneous fur mutants obtained in S. maltophilia. F60 produced higher amounts of biofilms than K279a and CLSM analysis demonstrated improved adherence and biofilm organization. Under iron restricted conditions, K279a produced biofilms with more biomass and enhanced thickness. In addition, F60 produced higher amounts of EPS than K279a but with a similar composition, as revealed by ATR-FTIR spectroscopy. With respect to the oxidative stress response, MnSOD was the only SOD isoenzyme detected in K279a. F60 presented higher SOD activity than the wt strain in planktonic and biofilm cultures, and iron deprivation increased K279a SOD activity. Under iron starvation, SDS-PAGE profile from K279a presented two iron-repressed proteins. Mass spectrometry analysis revealed homology with FepA and another putative TonB-dependent siderophore receptor of K279a. In silico analysis allowed the detection of potential Fur boxes in the respective coding genes. K279a encodes the QS diffusible signal factor (DSF). Under iron restriction K279a produced higher amounts of DSF than under iron rich condition. Finally, F60 was more virulent than K279a in the Galleria mellonella killing assay. These results put in evidence that iron levels regulate, likely through the Fur system, S. maltophilia biofilm formation, oxidative stress response, OMPs expression, DSF production and virulence.
| S-EPMC4559654 | biostudies-literature
Project description:The Gram-negative bacterium Stenotrophomonas maltophilialives in diverse ecological niches. As a result of its formidable capabilities of forming biofilm and its resistance to multiple antibiotic agents, the bacterium is also a nosocomial pathogen of serious threat to the health of patients whose immune systems are suppressed or compromised. Besides the histidine kinase RpfC, the two-component signal transduction system (TCS), which is the canonical regulatory machinery used by most bacterial pathogens, has never been experimentally investigated inS. maltophilia Here, we annotated 62 putative histidine kinase genes in the S. maltophilia genome and successfully obtained 51 mutants by systematical insertional inactivation. Phenotypic characterization identified a series of mutants with deficiencies in bacterial growth, swimming motility, and biofilm development. A TCS, named here BfmA-BfmK (Smlt4209-Smlt4208), was genetically confirmed to regulate biofilm formation inS. maltophilia Together with interacting partner prediction and chromatin immunoprecipitation screens, six candidate promoter regions bound by BfmA in vivo were identified. We demonstrated that, among them, BfmA acts as a transcription factor that binds directly to the promoter regions of bfmA-bfmK and Smlt0800(acoT), a gene encoding an acyl coenzyme A thioesterase that is associated with biofilm development, and positively controls their transcription. Genome-scale mutational analyses of histidine kinase genes and functional dissection of BfmK-BfmA regulation in biofilm provide genetic information to support more in-depth studies on cellular signaling inS. maltophilia, in the context of developing novel approaches to fight this important bacterial pathogen.
| S-EPMC4959488 | biostudies-literature
Project description:Recent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analyse an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.
| S-EPMC7184733 | biostudies-literature
Project description:Stenotrophomonas maltophilia is a Gram-negative bacterial pathogen of increasing concern to human health. Most clinical isolates of S. maltophilia efficiently form biofilms on biotic and abiotic surfaces, making this bacterium resistant to a number of antibiotic treatments and therefore difficult to eliminate. To date, very few studies have investigated the molecular and regulatory mechanisms responsible for S. maltophilia biofilm formation. Here we constructed a random transposon insertion mutant library of S. maltophilia ATCC 13637 and screened 14,028 clones. A total of 46 nonredundant genes were identified. Mutants of these genes exhibited marked changes in biofilm formation, suggesting that multiple physiological pathways, including extracellular polysaccharide production, purine synthesis, transportation, and peptide and lipid synthesis, are involved in bacterial cell aggregation. Of these genes, 20 putatively contributed to flagellar biosynthesis, indicating a critical role for cell motility in S.maltophilia biofilm formation. Genetic and biochemical evidence demonstrated that an orphan response regulator, FsnR, activated transcription of at least two flagellum-associated operons by directly binding to their promoters. This regulatory protein plays a fundamental role in controlling flagellar assembly, cell motility, and biofilm formation. These results provide a genetic basis to systematically study biofilm formation of S. maltophilia.
| S-EPMC4309692 | biostudies-other
Project description:Most studies on bacterial virulence focus on the pathogen itself. However, it is important to recall that the in-host behavior and the virulence of bacterial pathogens constitute a complex situation that depends on both the microorganisms and the infected host. While healthy people (the community) is infected by classical pathogenic microorganisms, able to cope with the anti-infection defenses of the host, in the case of people with basal diseases, debilitated or immunodepressed, the range of pathogens able to cause infection is wider and includes the so-named opportunistic pathogens, which lack the inherent ability to cause disease in healthy hosts and rarely produce infections in the community. Some of the most relevant opportunistic pathogens, as Stenotrophomonas maltophilia, have an environmental origin and, in occasions, present interesting biotechnological properties. Consequently, it is important knowing whether S. maltophilia isolates recovered from infections constitute a specific phylogenetic branch that has evolved toward acquiring a virulent phenotype as it happens in the case of classical pathogens or rather, any member of this bacterial species is capable of producing infection and its pathogenic behavior is mainly a consequence of the host situation. To address this question, we analyzed a set of environmental and clinical S. maltophilia strains. Our results indicate that this opportunistic pathogen presents a large core genome and that the distribution of genes in general, and of known virulence determinants in particular, is similar among environmental and clinical isolates. The majority of genes not belonging to the S. maltophilia core genome are present in just one or two of the analyzed strains. This indicates that, more than speciation into different lineages (virulent and environmental), the evolution of S. maltophilia is based in the strain-specific acquisition of genes, likely involved in the adaptation of this bacterial species to different microniches. In addition, both environmental and clinical isolates present low susceptibility to several antimicrobials. Altogether our results support that S. maltophilia does not present a specific evolutionary branch toward virulence and most likely infection is mainly the consequence of the impaired anti-infective response of the infected patients.
| S-EPMC5684188 | biostudies-literature
Project description:Stenotrophomonas maltophilia is an important opportunistic pathogen affecting primarily hospitalized and immuno-compromised hosts. We constructed an hfq deletion mutant (Delta-hfq) of S. maltophilia, and compared the behaviour of wild-type and Delta-hfq S. maltophilia cells in a variety of assays. Differential RNA sequencing analysis (dRNA-seq) of RNA isolated from S. maltophilia wild-type and Delta-hfq strains showed that Hfq regulates expression of genes encoding flagellar and fimbrial components, transmembrane proteins, as well as enzymes involved in different metabolic pathways. Moreover, we analysed expression of several sRNAs identified by dRNA-seq in wild-type. The accumulation of two sRNAs was strongly reduced in the absence of Hfq. TEX (terminator exonuclease) treated and untreated libraries of the wild type and the Delta-hfq mutant were sequenced and compared
2012-10-02 | E-GEOD-39705 | biostudies-arrayexpress
Project description:Outer membrane vesicles (OMVs) are small nanoscale structures that are secreted by bacteria and that can carry nucleic acids, proteins, and small metabolites. They can mediate intracellular communication and play a role in virulence. In this study, we show that treatment with the β-lactam antibiotic imipenem leads to a dramatic increase in the secretion of outer membrane vesicles in the nosocomial pathogen Stenotrophomonas maltophilia. Proteomic analysis of their protein content demonstrated that the OMVs contain the chromosomal encoded L1 metallo-β-lactamase and L2 serine-β-lactamase. Moreover, the secreted OMVs contain large amounts of two Ax21 homologs, i.e., outer membrane proteins known to be involved in virulence and biofilm formation. We show that OMV secretion and the levels of Ax21 in the OMVs are dependent on the quorum sensing diffusible signal system (DSF). More specific, we demonstrate that the S. maltophilia DSF cis-Δ2-11-methyl-dodecenoic acid and, to a lesser extent, the Burkholderia cenocepacia DSF cis-Δ2-dodecenoic acid, stimulate OMV secretion. By a targeted proteomic analysis, we confirmed that DSF-induced OMVs contain large amounts of the Ax21 homologs, but not the β-lactamases. This work illustrates that both quorum sensing and disturbance of the peptidoglycan biosynthesis provoke the release of OMVs and that OMV content is context dependent.
| S-EPMC4396451 | biostudies-literature