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

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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Kinetics of Bacterial Inactivation by Peroxynitric Acid in the Presence of Organic Contaminants

Applied and Environmental Microbiology ◽

10.1128/aem.01860-20 ◽

2020 ◽

Vol 87 (2) ◽

Author(s):

Takashi Yokoyama ◽

Shinya Miyazaki ◽

Hiroko Akagi ◽

Satoshi Ikawa ◽

Katsuhisa Kitano

Keyword(s):

Amino Acid ◽

Human Body ◽

Bactericidal Activity ◽

Organic Contaminants ◽

Biological Fluids ◽

Bactericidal Effect ◽

Amino Acid Residues ◽

Bacterial Inactivation ◽

Peroxynitric Acid ◽

Dose Dependent

ABSTRACT Low-temperature atmospheric-pressure plasma has been studied for disinfection purposes. When plasma is exposed to water, reactive oxygen and nitrogen species are generated and preserved in the water fraction (plasma-treated water [PTW]), which consequently exhibits bactericidal activity. At low temperatures, one of the bactericidal components of PTW is peroxynitric acid (PNA). Importantly, PNA can also be synthesized by chemical reaction, without exposure to plasma. In this study, we evaluated the bactericidal properties of PNA based on reaction kinetics in comparison with other disinfectants. The analysis, based on dose-dependent effects, showed that PNA exhibited about 1 and 10 times the bactericidal activity of hypochlorous acid (HOCl) and peracetic acid, respectively. In addition, we evaluated the influence of organic contaminants on the bactericidal effects of PNA and HOCl. The bactericidal potential of both disinfectants was reduced by bovine serum albumin (BSA); however, PNA showed about 30-times-higher resistance against BSA inhibition than HOCl. Analysis of the dose-dependent effects of PNA revealed that the inhibition of bactericidal effect was caused by its consumption. Further experiments using model substrates containing particular amino acid residues (Met, Cys, Lys, and Leu) suggested that the bacterial inactivation by PNA is less affected by BSA due to the low reactivity and narrow reactivity spectrum of PNA for amino acid residues. Overall, our results suggest that PNA has a great disinfection potential, especially in the presence of organic contaminants (e.g., on the surface of the human body and on medical instruments contaminated with biological fluids). IMPORTANCE A good disinfectant for the human body should have various properties, such as strong bactericidal activity, harmlessness to living tissues, and resistance against biological fluids (or other organic contaminants). Peroxynitric acid (PNA) showed a bactericidal effect that was several tens up to several hundred times higher per unit of molarity than that of sodium hypochlorite and peracetic acid, which are used as general disinfectants for medical equipment. Moreover, the high resistance of PNA to organic load was confirmed, indicating that PNA will inactivate bacteria effectively even on contaminated surfaces, such as used medical devices or the human body surface. Therefore, we propose that PNA can be used as a strong disinfectant for the human body.

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A Fish Galectin-8 Possesses Direct Bactericidal Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22010376 ◽

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.50.2.806-809.2006 ◽

2006 ◽

Vol 50 (2) ◽

pp. 806-809 ◽

Cited By ~ 80

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.

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Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children

Science Immunology ◽

10.1126/sciimmunol.aau8125 ◽

2019 ◽

Vol 4 (32) ◽

pp. eaau8125 ◽

Cited By ~ 17

Author(s):

Alexandra Paun ◽

Christopher Yau ◽

Shahab Meshkibaf ◽

Michelle C. Daigneault ◽

Leili Marandi ◽

...

Keyword(s):

Biological Fluids ◽

Bacterial Species ◽

Antibody Responses ◽

Therapeutic Interventions ◽

Islet Autoimmunity ◽

Islet Autoantibody ◽

Dependent Manner ◽

Bacterial Strains ◽

Intestinal Microbes ◽

Pediatric Study

Microbiome sequence analyses have suggested that changes in gut bacterial composition are associated with autoimmune disease in humans and animal models. However, little is known of the mechanisms through which the gut microbiota influences autoimmune responses to distant tissues. Here, we evaluated systemic antibody responses against cultured human gut bacterial strains to determine whether observed patterns of anticommensal antibody (ACAb) responses are associated with type 1 diabetes (T1D) in two cohorts of pediatric study participants. In the first cohort, ACAb responses in sera collected from participants within 6 months of T1D diagnosis were compared with age-matched healthy controls and also with patients with recent onset Crohn’s disease. ACAb responses against multiple bacterial species discriminated among these three groups. In the second cohort, we asked whether ACAb responses present before diagnosis were associated with later T1D development and with HLA genotype in participants who were discordant for subsequent progression to diabetes. Serum IgG2 antibodies against Roseburia faecis and against a bacterial consortium were associated with future T1D diagnosis in an HLA DR3/DR4 haplotype–dependent manner. These analyses reveal associations between antibody responses to intestinal microbes and HLA-DR genotype and islet autoantibody specificity and with a future diagnosis of T1D. Further, we present a platform to investigate antibacterial antibodies in biological fluids that is applicable to studies of autoimmune diseases and responses to therapeutic interventions.

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Bactericidal Activity of Glycinecin A, a Bacteriocin Derived from Xanthomonas campestris pv. glycines, on Phytopathogenic Xanthomonas campestris pv. vesicatoria Cells

Applied and Environmental Microbiology ◽

10.1128/aem.70.8.4486-4490.2004 ◽

2004 ◽

Vol 70 (8) ◽

pp. 4486-4490 ◽

Cited By ~ 16

Author(s):

Huy Thang Pham ◽

Key Zoung Riu ◽

Kong Man Jang ◽

Somi K. Cho ◽

Moonjae Cho

Keyword(s):

Membrane Potential ◽

Cause Of Death ◽

Mechanism Of Action ◽

Bactericidal Activity ◽

Xanthomonas Campestris ◽

Potassium Ions ◽

Dependent Manner ◽

Bacterial Cells ◽

Ion Efflux ◽

Dose Dependent

ABSTRACT The ability of glycinecin A, a bacteriocin derived from Xanthomonas campestris pv. glycines 8ra, to kill closely related bacteria has been demonstrated previously by our group (S. G. Heu et al., Appl. Environ. Microbiol. 67:4105-4110, 2001). In the present study, we aimed at determining the glycinecin A-induced cause of death. Treatment with glycinecin A caused slow dissipation of membrane potential and rapid depletion of the pH gradient. Glycinecin A treatment also induced leakage of potassium ions from X. campestris pv. vesicatoria YK93-4 cells and killed sensitive bacterial cells in a dose-dependent manner. Sensitive cells were killed within 2 h of incubation, most likely due to the potassium ion efflux caused by glycinecin A. These results suggest that the bactericidal mechanism of action of glycinecin A is correlated with the permeability of membranes to hydroxyl and potassium ions, leading to the lethal activity of the bacteriocin on the target bacteria.

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Efficacy of piperacillin in combination with novel β-lactamase inhibitor IID572 against β-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa026 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1530-1536

Author(s):

E J Growcott ◽

L Gamboa ◽

T Roth ◽

S Lopez ◽

C S Osborne

Keyword(s):

Staphylococcus Aureus ◽

Infection Model ◽

Dependent Manner ◽

Bacterial Strains ◽

Bacterial Reduction ◽

Class A ◽

Infection Models ◽

Dose Dependent ◽

And Staphylococcus Aureus ◽

Lactamase Inhibitor

Abstract Objectives The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel β-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various β-lactamase enzymes. Methods Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of β-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated. Results In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D β-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing β-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested. Conclusions In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with β-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.

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Enhanced Bactericidal Activity of Rifampin and/or Pyrazinamide When Combined with PA-824 in a Murine Model of Tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00686-08 ◽

2008 ◽

Vol 52 (10) ◽

pp. 3664-3668 ◽

Cited By ~ 52

Author(s):

Rokeya Tasneen ◽

Sandeep Tyagi ◽

Kathy Williams ◽

Jacques Grosset ◽

Eric Nuermberger

Keyword(s):

Phase Ii ◽

Bactericidal Activity ◽

Murine Model ◽

Drug Combination ◽

Synergistic Activity ◽

Dependent Manner ◽

First Line ◽

Phase Ii Clinical Trials ◽

Dose Dependent ◽

Culture Negative

ABSTRACT PA-824 is in phase II clinical testing to treat tuberculosis. At a dose of 100 mg/kg of body weight, it has demonstrated bactericidal activity during the initial and continuation phases of treatment in a murine model of tuberculosis. In a prior study, substitution of PA-824 for isoniazid in the first-line regimen of rifampin, isoniazid, and pyrazinamide resulted in significantly lower CFU counts at 2 months and shorter time to culture-negative conversion. However, the study design prevented a rigorous assessment of the relapse rate after completion of therapy. The current experiment was designed to assess (i) the extent of the beneficial effect of substituting PA-824 for isoniazid in the first-line regimen, (ii) the influence of the PA-824 dose on the same effect, and (iii) the activity of each one-, two-, and three-drug combination of rifampin, PA-824, and pyrazinamide. Mice were infected by the aerosol route and initiated on treatment 14 days later with more than 7 log10 CFU per lung. Treatment with rifampin and pyrazinamide was more effective than treatment with rifampin, isoniazid, and pyrazinamide at reducing the lung CFU count, consistent with past evidence of isoniazid's antagonism in this model. The addition of PA-824 at 12.5 and 25 mg/kg/day did not increase the activity of rifampin plus pyrazinamide, but the addition of PA-824 at 50 and 100 mg/kg/day did increase the activity in a dose-dependent manner. The combination of rifampin, PA-824 (100 mg/kg), and pyrazinamide rendered all mice culture negative after 2 months of treatment and free of relapse after 4 months of treatment, while some mice receiving rifampin, isoniazid, and pyrazinamide remained culture positive and 15% relapsed after completing 4 months of treatment. The two-drug combination of PA-824 and pyrazinamide displayed synergistic activity that was equivalent to that of the standard first-line regimen. Together, these results support the evaluation of regimens based on the combination of rifampin, PA-824, and pyrazinamide in phase II clinical trials while demonstrating several potential pitfalls in the evaluation of new drug combinations in a murine model of tuberculosis.

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Antibacterial potential of venom extracted from wolf spider, Lycosa terrestris (Araneae: Lycosiade)

Indian Journal of Animal Research ◽

10.18805/ijar.v0iof.8484 ◽

2017 ◽

Cited By ~ 2

Author(s):

Hafiz Muhammad Tahir ◽

Arooj Zaheer ◽

Azhar Khan ◽

Mazhar Abbas

Keyword(s):

Wolf Spider ◽

Dependent Manner ◽

Bacterial Strains ◽

Toxic Compounds ◽

Gram Negative ◽

Acinetobacter Sp ◽

Susceptibility Tests ◽

Dose Dependent ◽

Predatory Potential ◽

Antibacterial Potential

The wolf spider Lycosa terrestris (Araneae: Lycosidae) is a well known arthropod containing toxic compounds. It has significant predatory potential in addition to its uses in medicinal and insecticidal formulation. Current investigations were aimed to extract and partially characterize the venom of L. terrestris and the susceptibility tests to evaluate antibacterial potential of venom supernatant and venom pellets against four pathogenic bacterial strains i.e., Gram negative Acinetobacter sp. and Pasteurella sp. and Gram Positive Staphylococcus sp. and Streptococcus sp. Results of this study revealed that the venom of L. terrestris contained six relatively high molecular weight peptides ranging from 125 kDa to 35 kDa. Moreover, results of the susceptibility test confirmed the bacteriostatic action of venom supernatant against aerobic Gram negative Acinetobacter sp. in dose dependent manner. A reduced trend of bacteriostatic inhibition was also observed for venom pellets against Acinetobacter sp

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Bactericidal Activity of Increasing Daily and Weekly Doses of Moxifloxacin in Murine Tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.6.1875-1879.2002 ◽

2002 ◽

Vol 46 (6) ◽

pp. 1875-1879 ◽

Cited By ~ 54

Author(s):

Tetsuyuki Yoshimatsu ◽

Eric Nuermberger ◽

Sandeep Tyagi ◽

Richard Chaisson ◽

William Bishai ◽

...

Keyword(s):

Bactericidal Activity ◽

Pharmacokinetic Profile ◽

Bactericidal Effect ◽

In Vivo Studies ◽

Pharmacokinetic Data ◽

Time Curve ◽

Pharmacodynamic Profile ◽

Days Of Therapy ◽

Dose Dependent

ABSTRACT Moxifloxacin (MXF) is a new 8-methoxyquinolone with potent activity against Mycobacterium tuberculosis and a half-life of 9 to 12 h in humans. Previous in vivo studies using daily doses of 100 mg/kg of body weight have demonstrated bactericidal activity comparable to that of isoniazid (INH) in a murine model of tuberculosis (TB). Recent pharmacokinetic data suggest that MXF may have been underadministered in these studies and that a 400-mg/kg dose in mice better approximates the area under the concentration-time curve obtained in humans after a 400-mg oral dose. Therefore, the bactericidal activity of MXF in doses up to 400 mg/kg given daily or weekly for 28 days was assessed in mice infected intravenously with 5 × 106 CFU of M. tuberculosis. INH was used as a positive control. After 3 days of daily therapy, the CFU counts from splenic homogenates for mice treated with MXF in doses of 100 to 400 mg/kg/day were lower than those from pretreatment controls. No significant differences in CFU counts were seen when mice receiving INH or MXF at 50 mg/kg/day were compared to pretreatment controls. After 28 days of therapy, dose-dependent reductions in CFU counts in splenic homogenates were seen for daily MXF therapy. The maximum bactericidal effect was seen with daily doses of 400 mg/kg, which resulted in a reduction in CFU counts of 1 log10 greater than that with INH treatment, although the difference was not statistically significant. CFU counts from lung homogenates after 28 days of therapy were significantly lower in all treatment groups than in untreated controls. The weekly administration of MXF in doses ranging from 50 to 400 mg/kg resulted in no significant bactericidal activity. Mice receiving daily MXF doses of 200 and 400 mg/kg/day failed to gain weight and appeared ill after 28 days of therapy, findings suggestive of drug toxicity. In conclusion, MXF has dose-dependent bactericidal activity against M. tuberculosis in the mouse when given in doses up to 400 mg/kg, where its pharmacokinetic profile better approximates that of standard human dosages. Combination regimens which take advantage of the enhanced pharmacodynamic profile of MXF at these doses have the potential to shorten the course of antituberculous therapy or allow more intermittent (i.e., once-weekly) therapy and should be evaluated in the mouse model of TB.

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