scholarly journals Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae , Resulting in Hypervirulence

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Claudia Trappetti ◽  
Lauren J. McAllister ◽  
Austen Chen ◽  
Hui Wang ◽  
Adrienne W. Paton ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Quorum Sensing ◽  
Capsular Polysaccharide ◽  
The Body ◽  
Gram Negative Bacteria ◽  
Phosphotransferase System ◽  
Gram Positive ◽  
Gram Negative ◽  
Autoinducer 2 ◽  
Leloir Pathway

ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS ( S -ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae , sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.

Novel volatiles of skin-borne bacteria inhibit the growth of Gram-positive bacteria and affect quorum-sensing controlled phenotypes of Gram-negative bacteria

2016 ◽  
Vol 39 (8) ◽  
pp. 503-515 ◽  
Author(s):  
Marie Chantal Lemfack ◽  
Srinivasa Rao Ravella ◽  
Nicola Lorenz ◽  
Marco Kai ◽  
Kirsten Jung ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

scholarly journals Recognition of Streptococcus pneumoniae and Muramyl Dipeptide by NOD2 Results in Potent Induction of MMP-9, Which Can Be Controlled by Lipopolysaccharide Stimulation

2014 ◽  
Vol 82 (12) ◽  
pp. 4952-4958 ◽  
Author(s):  
Marloes Vissers ◽  
Yvonne Hartman ◽  
Laszlo Groh ◽  
Dirk J. de Jong ◽  
Marien I. de Jonge ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mononuclear Cells ◽  
Muramyl Dipeptide ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Potent Inducer ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACTMatrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis duringStreptococcus pneumoniaeinfection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction byStreptococcus pneumoniaeand MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show thatStreptococcus pneumoniaeis able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved inStreptococcus pneumoniaepathogenesis.

scholarly journals Two Active Forms of UDP-N-Acetylglucosamine Enolpyruvyl Transferase in Gram-Positive Bacteria

2000 ◽  
Vol 182 (15) ◽  
pp. 4146-4152 ◽  
Author(s):  
Wensheng Du ◽  
James R. Brown ◽  
Daniel R. Sylvester ◽  
Jianzhong Huang ◽  
Alison F. Chalker ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Gene Duplication ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Double Deletion ◽  
Allelic Replacement ◽  
Genes Encoding ◽  
Bacterial Sources

ABSTRACT Gene sequences encoding the enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from many bacterial sources were analyzed. It was shown that whereas gram-negative bacteria have only one murA gene, gram-positive bacteria have two distinct genes encoding these enzymes which have possibly arisen from gene duplication. The twomurA genes of the gram-positive organismStreptococcus pneumoniae were studied further. Each of themurA genes was individually inactivated by allelic replacement. In each case, the organism was viable despite losing one of its murA genes. However, when attempts were made to construct a double-deletion strain, no mutants were obtained. This indicates that both genes encode active enzymes that can substitute for each other, but that the presence of a MurA function is essential to the organism. The two genes were further cloned and overexpressed, and the enzymes they encode were purified. Both enzymes catalyzed the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N-acetylglucosamine, confirming they are both active UDP-N-acetylglucosamine enolpyruvyl transferases. The catalytic parameters of the two enzymes were similar, and they were both inhibited by the antibiotic fosfomycin.

Structural comparison of the histidine-containing phosphocarrier protein HPr

1994 ◽  
Vol 72 (5-6) ◽  
pp. 202-217 ◽  
Author(s):  
Zongchao Jia ◽  
J. Wilson Quail ◽  
Louis T. J. Delbaere ◽  
E. Bruce Waygood
Keyword(s):  
Conformational Change ◽  
Active Center ◽  
Resonance Structure ◽  
Nuclear Magnetic Resonance Structure ◽  
Gram Negative Bacteria ◽  
Structural Comparison ◽  
Phosphotransferase System ◽  
Gram Positive ◽  
Gram Negative ◽  
X Ray

The phosphocarrier protein HPr is a central component of the bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) that is responsible for carbohydrate uptake in many bacterial species. A number of three-dimensional structures of HPrs from both Gram-positive and Gram-negative bacteria have been determined; the overall folding topology of HPr is an open-faced β-sandwich composed of three α-helices and a β-sheet. A detailed structural comparison of these HPrs has been carried out. Besides the overall main chain folding, many detailed structural features are well conserved in all HPr structures. The three x-ray structures of HPrs from Escherichia coli, Streptococcus faecalis, and Bacillus subtilis show considerable overall similarity with respect to the positions of the Cα atoms. A significant structural difference between HPrs from Gram-positive and Gram-negative bacteria is found in the region of Gly54, owing to the steric effects of Tyr37 in HPrs from the Gram-positive species. The region around Gly54 is involved in the binding of HPr to other PTS proteins and the differences in this region may be responsible for some of the poor functional complementation between HPrs from Gram-positive and Gram-negative species. The active center region, residues 12–18, appears to have significant differences in the comparisons between the overall structures. These differences support the proposal that phosphorylation and dephosphorylation of the active site His 15 is accompanied by conformational changes. However, a local structural comparison of residues 12–18 from the x-ray structures of HPrs from E. coli and B. subtilis, and the two-dimensional nuclear magnetic resonance structure of B. subtilis HPr suggests that there is a conserved active center involving residues His15, Arg 17, and Pro18, which shows little conformational change during the phosphorylation cycle. The results of other experimental approaches, including site-directed mutagenesis and NMR spectroscopy, are in some cases difficult to rationalize with some of the details of the structures, but do appear to favour the conclusion that little conformational change occurs.Key words: phosphoenolpyruvate: sugar phosphotransferase system, histidine-containing protein, active center, phosphorylation, protein structure, structural homology.

scholarly journals In VitroActivity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

2016 ◽  
Vol 60 (10) ◽  
pp. 6381-6385 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Michael D. Huband ◽  
David J. Farrell
Keyword(s):  
United States ◽  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
The United States ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type

ABSTRACTDelafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200Streptococcus pneumoniae(plus 30 levofloxacin-resistant isolates), 200Haemophilus influenzae, and 100Moraxella catarrhalisisolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50and MIC90values against allS. pneumoniaeisolates were 0.008 and 0.015 μg/ml. Delafloxacin susceptibility was not affected by β-lactamase status againstH. influenzaeandM. catarrhalis.

scholarly journals Biofilm Mode of Growth of Streptococcus intermedius Favored by a Competence-Stimulating Signaling Peptide

2004 ◽  
Vol 186 (18) ◽  
pp. 6327-6331 ◽  
Author(s):  
Fernanda C. Petersen ◽  
Daniele Pecharki ◽  
Anne A. Scheie
Keyword(s):  
Quorum Sensing ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Streptococcus Intermedius ◽  
Gram Negative ◽  
Culture Growth

ABSTRACT Gram-positive and gram-negative bacteria use quorum sensing to coordinate population behavior. In several streptococci, quorum sensing mediated by competence-stimulating peptides (CSP) is associated with development of competence for transformation. We show here that a synthetic CSP favored the biofilm mode of growth of Streptococcus intermedius without affecting the rate of culture growth.

scholarly journals Quorum sensing signal autoinducer-2 inhibits sporulation of Bacillus by interacting with RapC and functions across species

2021 ◽  
Author(s):  
Qin Xiong ◽  
Huihui Zhang ◽  
Xia Shu ◽  
Xiting Sun ◽  
Haichao Feng ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Root Colonization ◽  
Population Level ◽  
Regulation Mechanism ◽  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Gram Negative ◽  
Protein Protein Interaction ◽  
Autoinducer 2 ◽  
Mutant Strains

Collective behavior of bacteria is regulated by quorum sensing (QS). Bacterial cells sense the density of ?the population and induce corresponding traits and developmental processes. Autoinducer-2 (AI-2) is a common QS signal that regulates behavior of both Gram-positive and Gram-negative bacteria. In spite of the plethora of processes described to be influenced by AI-2 in diverse Gram-negative bacteria, the AI-2-regulated processes in Bacilli are relatively unexplored. Previously, we demonstrated that AI-2 regulates root colonization of Bacillus velezensis SQR9, a well-studied plant beneficial rhizobacterium. Here, we describe a novel function for AI-2 in B. velezensis SQR9 related to development of dormant spores. AI-2 inhibited the initiation of spore development throught the phosphatase RapC and the DNA binding regulator ComA. Using mutant strains and protein-protein interaction studies, we demonstrate that AI-2 interacts with RapC to stimulate its binding to ComA and therefore inactive ComA. We further demonstrate that ComA is essential for Spo0A-regulated sporulation in B. velezensis SQR9. Finally, the AI-2 molecule could be shared cross species for inhibiting Bacillus sporulation. Our study revealed a novel function and regulation mechanism of AI-2 in sporulation inhibition of Bacilli that overall suggests sporulation to be a population-level decision process in Bacilli rather than just a individual cell behavior.

scholarly journals Replacement of l-Amino Acids by d-Amino Acids in the Antimicrobial Peptide Ranalexin and Its Consequences for Antimicrobial Activity and Biodistribution

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2987 ◽  
Author(s):  
Cornelius Domhan ◽  
Philipp Uhl ◽  
Christian Kleist ◽  
Stefan Zimmermann ◽  
Florian Umstätter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
The Body ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Strong Antimicrobial Activity

Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action are urgently needed. Ranalexin is a potent antimicrobial peptide (AMP) produced in the skin of the American bullfrog Rana catesbeiana. Despite strong antimicrobial activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, a ranalexin derivative consisting exclusively of d-amino acids (named danalexin) was synthesized and compared to the original ranalexin for its antimicrobial potential and its biodistribution properties in a rat model. Danalexin showed improved biodistribution with an extended retention in the organisms of Wistar rats when compared to ranalexin. While ranalexin is rapidly cleared from the body, danalexin is retained primarily in the kidneys. Remarkably, both peptides showed strong antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria of the genus Acinetobacter with minimum inhibitory concentrations (MICs) between 4 and 16 mg/L (1.9–7.6 µM). Moreover, both peptides showed lower antimicrobial activities with MICs ≥32 mg/L (≥15.2 µM) against further Gram-negative bacteria. The preservation of antimicrobial activity proves that the configuration of the amino acids does not affect the anticipated mechanism of action, namely pore formation.

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