scholarly journals A Fish Galectin-8 Possesses Direct Bactericidal Activity

2020 ◽  
Vol 22 (1) ◽  
pp. 376
Author(s):  
Tengfei Zhang ◽  
Shuai Jiang ◽  
Li Sun
Keyword(s):  
Bactericidal Activity ◽  
Bacterial Pathogens ◽  
Bactericidal Effect ◽  
Immune Defense ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Animal Cells ◽  
Gram Negative ◽  
Tongue Sole ◽  
Wide Range

Galectins are a family of animal lectins with high affinity for β-galactosides. Galectins are able to bind to bacteria, and a few mammalian galectins are known to kill the bound bacteria. In fish, no galectins with direct bactericidal effect have been reported. In the present study, we identified and characterized a tandem repeat galectin-8 from tongue sole Cynoglossus semilaevis (designated CsGal-8). CsGal-8 possesses conserved carbohydrate recognition domains (CRDs), as well as the conserved HXNPR and WGXEE motifs that are critical for carbohydrate binding. CsGal-8 was constitutively expressed in nine tissues of tongue sole and up-regulated in kidney, spleen, and blood by bacterial challenge. When expressed in HeLa cells, CsGal-8 protein was detected both in the cytoplasm and in the micro-vesicles secreted from the cells. Recombinant CsGal-8 (rCsGal-8) bound to lactose and other carbohydrates in a dose dependent manner. rCsGal-8 bound to a wide range of gram-positive and gram-negative bacteria and was co-localized with the bound bacteria in animal cells. Lactose, fructose, galactose, and trehalose effectively blocked the interactions between rCsGal-8 and different bacteria. Furthermore, rCsGal-8 exerted potent bactericidal activity against some gram-negative bacterial pathogens by directly damaging the membrane and structure of the pathogens. Taken together, these results indicate that CsGal-8 likely plays an important role in the immune defense against some bacterial pathogens by direct bacterial interaction and killing.

scholarly journals In Vitro Bactericidal Activity of Human β-Defensin 3 against Multidrug-Resistant Nosocomial Strains

2006 ◽  
Vol 50 (2) ◽  
pp. 806-809 ◽  
Author(s):  
Giuseppantonio Maisetta ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
Walter Florio ◽  
Daria Bottai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Bactericidal Activity ◽  
Stenotrophomonas Maltophilia ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative

ABSTRACT The antimicrobial activity of human β-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains.

scholarly journals Inhibition of Fosfomycin Resistance Protein FosA by Phosphonoformate (Foscarnet) in Multidrug-Resistant Gram-Negative Pathogens

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Ryota Ito ◽  
Adam D. Tomich ◽  
Christi L. McElheny ◽  
Roberta T. Mettus ◽  
Nicolas Sluis-Cremer ◽  
...  
Keyword(s):  
Antiviral Agent ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Dependent Manner ◽  
Kinetic Measurements ◽  
Gram Negative ◽  
Content Type ◽  
Clinical Strains ◽  
Fosfomycin Resistance ◽  
Time Kill

ABSTRACT FosA proteins confer fosfomycin resistance to Gram-negative pathogens via glutathione-mediated modification of the antibiotic. In this study, we assessed whether inhibition of FosA by sodium phosphonoformate (PPF) (foscarnet), a clinically approved antiviral agent, would reverse fosfomycin resistance in representative Gram-negative pathogens. The inhibitory activity of PPF against purified recombinant FosA from Escherichia coli (FosA3), Klebsiella pneumoniae (FosAKP), Enterobacter cloacae (FosAEC), and Pseudomonas aeruginosa (FosAPA) was determined by steady-state kinetic measurements. The antibacterial activity of PPF against FosA in clinical strains of these species was evaluated by susceptibility testing and time-kill assays. PPF increased the Michaelis constant (Km ) for fosfomycin in a dose-dependent manner, without affecting the maximum rate (V max) of the reaction, for all four FosA enzymes tested, indicating a competitive mechanism of inhibition. Inhibitory constant (Ki ) values were 22.6, 35.8, 24.4, and 56.3 μM for FosAKP, FosAEC, FosAPA, and FosA3, respectively. Addition of clinically achievable concentrations of PPF (∼667 μM) reduced the fosfomycin MICs by ≥4-fold among 52% of the K. pneumoniae, E. cloacae, and P. aeruginosa clinical strains tested and led to a bacteriostatic or bactericidal effect in time-kill assays among representative strains. PPF inhibits FosA activity across Gram-negative species and can potentiate fosfomycin activity against the majority of strains with chromosomally encoded fosA. These data suggest that PPF may be repurposed as an adjuvant for fosfomycin to treat infections caused by some FosA-producing, multidrug-resistant, Gram-negative pathogens.

scholarly journals Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms

1980 ◽  
Vol 28 (3) ◽  
pp. 893-898
Author(s):  
R R Arnold ◽  
M Brewer ◽  
J J Gauthier
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bactericidal Activity ◽  
Brain Heart Infusion ◽  
Bactericidal Effect ◽  
Resistant Bacteria ◽  
Avirulent Strain ◽  
Iron Binding ◽  
Gram Negative ◽  
Mucosal Tissues ◽  
Iron Binding Protein

Lactoferrin is an iron-binding protein that has been detected in secretions that bathe human mucosal tissues. Previous studies have shown that, when this protein is in the iron-free state, it is capable of a direct bactericidal effect on Streptococcus mutans and Vibrio cholerae. The present study demonstrates variable susceptibilities for a variety of different microorganisms. The list of susceptible organisms includes gram-positive and gram-negative microbes, rods and cocci, facultative anaerobes, and aerotolerant anaerobes. Similar morphological and physiological types are represented among the lalctoferrin-resistant bacteria. S. mutans was more resistant to lactoferrin when grown on a sucrose-contaning medium than when it was grown on brain heart infusion broth without added scurose. When a lactoferrin-sensitive, avirulent strain of Streptococcus pneumoniae was passed through mice, the resultant virulent culture became lactoferrin resistant. Since organisms of the same species and even of the same strain (S. pneumoniae) can differ in susceptibility to lactoferrin, it appears that accessibility to the lactoferrin target site may account for differences in susceptibility. It appears that there may be a relation between virulence and resistance to lactoferrin.

scholarly journals Characterization of the Putative Type III Secretion ATPase CdsN (Cpn0707) of Chlamydophila pneumoniae

2008 ◽  
Vol 190 (20) ◽  
pp. 6580-6588 ◽  
Author(s):  
Chris B. Stone ◽  
Dustin L. Johnson ◽  
David C. Bulir ◽  
Jodi D. Gilchrist ◽  
James B. Mahony
Keyword(s):  
Atpase Activity ◽  
Type Iii Secretion ◽  
Sequence Similarity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Chlamydophila Pneumoniae ◽  
Effector Proteins ◽  
Dependent Manner ◽  
Gram Negative ◽  
Type Iii ◽  
Wide Range

ABSTRACT Type III secretion (T3S) is utilized by a wide range of gram-negative bacterial pathogens to allow the efficient delivery of effector proteins into the host cell cytoplasm through the use of a syringe-like injectisome. Chlamydophila pneumoniae is a gram-negative, obligate intracellular pathogen that has the structural genes coding for a T3S system, but the functionality of the system has not yet been demonstrated. T3S is dependent on ATPase activity, which catalyzes the unfolding of proteins and the secretion of effector proteins through the injectisome. CdsN (Cpn0707) is predicted to be the T3S ATPase of C. pneumoniae based on sequence similarity to other T3S ATPases. Full-length CdsN and a C-terminal truncation of CdsN were cloned as glutathione S-transferase (GST)-tagged constructs and expressed in Escherichia coli. The GST-tagged C-terminal truncation of CdsN possessed ATPase activity, catalyzing the release of ADP and Pi from ATP at a rate of 0.55 ± 0.07 μmol min−1 mg−1 in a time- and dose-dependent manner. CdsN formed oligomers and high-molecular-weight multimers, as assessed by formaldehyde fixation and nondenaturing polyacrylamide gel electrophoresis. Using bacterial two-hybrid and GST pull-down assays, CdsN was shown to interact with CdsD, CdsL, CdsQ, and CopN, four putative structural components of the C. pneumoniae T3S system. CdsN also interacted with an unannotated protein, Cpn0706, a putative CdsN chaperone. Interactions between CdsN, CdsD, and CopN represent novel interactions not previously reported for other bacterial T3S systems and may be important in the localization and/or function of the ATPase at the inner membrane of C. pneumoniae.

scholarly journals Shared and Unique Evolutionary Trajectories to Ciprofloxacin Resistance in Gram-negative Bacterial Pathogens

2021 ◽  
Author(s):  
Jaime E. Zlamal ◽  
Semen A Leyn ◽  
Mallika Iyer ◽  
Marinela Elane ◽  
Nicholas A Wong ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Bacterial Pathogens ◽  
Genetic Alterations ◽  
Bacterial Populations ◽  
Gram Negative ◽  
Acquired Drug Resistance ◽  
Wide Range ◽  
Evolutionary Trajectories ◽  
Ciprofloxacin Resistance

The resistance to broad-spectrum antibiotic ciprofloxacin is detected in high rates for a wide range of bacterial pathogens. To investigate dynamics of ciprofloxacin resistance development we proposed a comparative resistomics workflow for three clinically relevant species of Gram-negative bacteria: Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. We combined experimental evolution in a morbidostat with deep sequencing of evolving bacterial populations in time series that reveals both shared and unique aspects of evolutionary trajectories patterns. Representative clone characterization by sequencing and MIC measurements enabled direct assessment of mutations impact on the extent of acquired drug resistance. In all three species we observed a two-stage evolution: (1) early ciprofloxacin resistance reaching 4-16-fold of wildtype MIC commonly as a result of single mutations in DNA gyrase target genes (gyrA or gyrB) and (2) additional genetic alterations affecting transcriptional control of drug efflux machinery or secondary target genes (DNA topoisomerase parC or parE).

scholarly journals PorZ, an Essential Component of the Type IX Secretion System of Porphyromonas gingivalis, Delivers Anionic Lipopolysaccharide to the PorU Sortase for Transpeptidase Processing of T9SS Cargo Proteins

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mariusz Madej ◽  
Zuzanna Nowakowska ◽  
Miroslaw Ksiazek ◽  
Anna M. Lasica ◽  
Danuta Mizgalska ◽  
...  
Keyword(s):  
Cell Surface ◽  
Porphyromonas Gingivalis ◽  
Secretion System ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Content Type ◽  
Essential Component ◽  
Wide Range ◽  
Cargo Proteins ◽  
Type Ix Secretion System

ABSTRACT Cargo proteins of the type IX secretion system (T9SS) in human pathogens from the Bacteroidetes phylum invariably possess a conserved C-terminal domain (CTD) that functions as a signal for outer membrane (OM) translocation. In Porphyromonas gingivalis, the CTD of cargos is cleaved off after translocation, and anionic lipopolysaccharide (A-LPS) is attached. This transpeptidase reaction anchors secreted proteins to the OM. PorZ, a cell surface-associated protein, is an essential component of the T9SS whose function was previously unknown. We recently solved the crystal structure of PorZ and found that it consists of two β-propeller moieties, followed by a CTD. In this study, we performed structure-based modeling, suggesting that PorZ is a carbohydrate-binding protein. Indeed, we found that recombinant PorZ specifically binds A-LPS in vitro. Binding was blocked by monoclonal antibodies that specifically react with a phosphorylated branched mannan in the anionic polysaccharide (A-PS) component of A-LPS, but not with the core oligosaccharide or the lipid A endotoxin. Examination of A-LPS derived from a cohort of mutants producing various truncations of A-PS confirmed that the phosphorylated branched mannan is indeed the PorZ ligand. Moreover, purified recombinant PorZ interacted with the PorU sortase in an A-LPS-dependent manner. This interaction on the cell surface is crucial for the function of the “attachment complex” composed of PorU, PorZ, and the integral OM β-barrel proteins PorV and PorQ, which is involved in posttranslational modification and retention of T9SS cargos on the bacterial surface. IMPORTANCE Bacteria have evolved multiple systems to transport effector proteins to their surface or into the surrounding milieu. These proteins have a wide range of functions, including attachment, motility, nutrient acquisition, and toxicity in the host. Porphyromonas gingivalis, the human pathogen responsible for severe gum diseases (periodontitis), uses a recently characterized type IX secretion system (T9SS) to translocate and anchor secreted virulence effectors to the cell surface. Anchorage is facilitated by sortase, an enzyme that covalently attaches T9SS cargo proteins to a unique anionic lipopolysaccharide (A-LPS) moiety of P. gingivalis. Here, we show that the T9SS component PorZ interacts with sortase and specifically binds A-LPS. Binding is mediated by a phosphorylated branched mannan repeat in A-LPS polysaccharide. A-LPS-bound PorZ interacts with sortase with significantly higher affinity, facilitating modification of cargo proteins by the cell surface attachment complex of the T9SS.

scholarly journals Inactivation of Bacterial Pathogens following Exposure to Light from a 405-Nanometer Light-Emitting Diode Array

2009 ◽  
Vol 75 (7) ◽  
pp. 1932-1937 ◽  
Author(s):  
Michelle Maclean ◽  
Scott J. MacGregor ◽  
John G. Anderson ◽  
Gerry Woolsey
Keyword(s):  
Staphylococcus Aureus ◽  
Light Emitting Diode ◽  
Bacterial Pathogens ◽  
Light Illumination ◽  
Population Densities ◽  
Gram Positive ◽  
Gram Negative ◽  
Light Emitting ◽  
Led Array ◽  
Wide Range

ABSTRACT This study demonstrates the susceptibility of a variety of medically important bacteria to inactivation by 405-nm light from an array of light-emitting diodes (LEDs), without the application of exogenous photosensitizer molecules. Selected bacterial pathogens, all commonly associated with hospital-acquired infections, were exposed to the 405-nm LED array, and the results show that both gram-positive and gram-negative species were successfully inactivated, with the general trend showing gram-positive species to be more susceptible than gram-negative bacteria. Detailed investigation of the bactericidal effect of the blue-light treatment on Staphylococcus aureus suspensions, for a range of different population densities, demonstrated that 405-nm LED array illumination can cause complete inactivation at high population densities: inactivation levels corresponding to a 9-log10 reduction were achieved. The results, which show the inactivation of a wide range of medically important bacteria including methicillin-resistant Staphylococcus aureus, demonstrate that, with further development, narrow-spectrum 405-nm visible-light illumination from an LED source has the potential to provide a novel decontamination method with a wide range of potential applications.

scholarly journals Susceptibility of Streptococcusmutans and Actinobacillusactinomycetemcomitans to Bactericidal Activity of Human β-Defensin 3 in Biological Fluids

2005 ◽  
Vol 49 (3) ◽  
pp. 1245-1248 ◽  
Author(s):  
Giuseppantonio Maisetta ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
Giorgio Raco ◽  
Daria Bottai ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Biological Fluids ◽  
Local Treatment ◽  
Bactericidal Effect ◽  
Therapeutic Use ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Oral Infections ◽  
Dose Dependent

ABSTRACT Bactericidal activity of human β-defensin 3 (hBD-3) against Streptococcus mutans and Actinobacillus actinomycetemcomitans was inhibited in a dose-dependent manner by the presence of saliva and/or serum. Increasing the concentration of hBD-3 partially overcame this inhibition. A fast bactericidal effect was observed against both bacterial strains, suggesting a potential therapeutic use for hBD-3 in the local treatment of oral infections.

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