scholarly journals Bactericidal Activity of Octenidine to Various Genospecies of Borrelia burgdorferi, Sensu Lato Spirochetes in Vitro and in Vivo

2017 ◽  
Vol 66 (2) ◽  
pp. 259-263 ◽  
Author(s):  
Stanisława Tylewska-Wierzbanowska ◽  
Urszula Roguska ◽  
Grażyna Lewandowska ◽  
Tomasz Chmielewski
Keyword(s):  
Borrelia Burgdorferi ◽  
Bactericidal Activity ◽  
Reliable Method ◽  
Bactericidal Effect ◽  
Sensu Stricto ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Bactericidal Action ◽  
Speed Up

The aim of our studies was to invent a reliable method for detection of bactericidal activity of disinfectants against Borrelia burgdorferi in suspension (in vitro) and in cell line cultures (in vivo). In the suspension method, 0.01 % octenidine at 20°C and 35°C was bactericidal to Borrelia afzeli; Borrelia garini, B. burgdorferi sensu stricto after 5 minutes treatment. Increase of the temperature to 35°C speed up the bactericidal effect to 1 minute. The bactericidal action of octenidine towards B. burgdorferi spirochetes growing in fibroblasts was less effective and needed a longer time to kill them than in the suspension.

Antibodies against Specific Proteins of and Immobilizing Activity against Three Strains of Borrelia burgdorferi Sensu Lato Can Be Found in Symptomatic but Not in Infected Asymptomatic Dogs

2000 ◽  
Vol 38 (7) ◽  
pp. 2611-2621 ◽  
Author(s):  
Joppe W. R. Hovius ◽  
K. Emil Hovius ◽  
Anneke Oei ◽  
Dirk J. Houwers ◽  
Alje P. van Dam
Keyword(s):  
Borrelia Burgdorferi ◽  
Acute Phase ◽  
Bactericidal Activity ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blots ◽  
Cell Enzyme ◽  
Specific Proteins ◽  
Different Strains

In an area where Lyme disease is endemic in The Netherlands all dogs had positive titers by whole-cell enzyme-linked immunosorbent assay and appeared to be naturally infected by Borrelia burgdorferi sensu lato. To compare the antibody responses of symptomatic dogs and asymptomatic controls, we performed Western blots and in vitro immobilization assays to study antibody-dependent bactericidal activity. Strains from three different genospecies were employed as the antigen source: B. burgdorferi strain B31,Borrelia garinii strain A87S, and Borrelia afzelii strain pKo. Antibodies against flagellin (p41) and p39 for three strains were found in sera from both symptomatic and asymptomatic dogs and were therefore considered to be markers of exposure. Antibodies against p56 and p30 of strain B31, against p75, p58, p50, OspC, and p<19 of strain A87S, and against p56, p54, p45, OspB, p31, p26, and p<19 of strain pKo were found significantly more frequently in sera from symptomatic dogs younger than 8 years when the first symptoms were observed than in those from age-matched controls (P < 0.01). These antibodies were not found in preclinical sera and appeared during development of disease. Antibodies against OspA of strains B31 and A87S were only seen in acute-phase and convalescent sera from three dogs that recovered from disease. Incubation with 25% normal canine serum did not result in the immobilization of strains B31 and pKo, but partial immobilization of strain A87S (61% ± 24% [standard deviation] at 5 h) occurred. Seven of 15 sera from symptomatic dogs but none of the sera from 11 asymptomatic dogs had antibody-dependent immobilizing activity against one of the strains. Consecutive sera from one of these dogs immobilized two different strains. Antibody-mediated bactericidal serum was not seen before onset of disease, was strongest in the acute phase of disease, and fluctuated during chronic disease. From seven out of eight symptomatic dogs Borrelia DNA was amplified by PCR; in three of them the bactericidal activity was directed against one of the genospecies amplified from that dog; however, four PCR-positive dogs lacked bactericidal activity. In conclusion, dogs with symptomatic canine borreliosis have more-extensive antibody reactivity against Borrelia, as shown by both Western blotting and immobilization assays.

scholarly journals Active and Passive Immunity against Borrelia burgdorferi Decorin Binding Protein A (DbpA) Protects against Infection

1998 ◽  
Vol 66 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
Mark S. Hanson ◽  
David R. Cassatt ◽  
Betty P. Guo ◽  
Nita K. Patel ◽  
Michael P. McCarthy ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Low Dose ◽  
Early Stage ◽  
Protein A ◽  
Sensu Stricto ◽  
Passive Immunity ◽  
In Vitro Growth

ABSTRACT Borrelia burgdorferi, the spirochete that causes Lyme disease, binds decorin, a collagen-associated extracellular matrix proteoglycan found in the skin (the site of entry for the spirochete) and in many other tissues. Two borrelial adhesins that recognize this proteoglycan, decorin binding proteins A and B (DbpA and DbpB, respectively), have recently been identified. Infection of mice by low-dose B. burgdorferi challenge elicited antibodies against DbpA and DbpB that were sustained at high levels, suggesting that these antigens are expressed in vivo. Scanning immunoelectron microscopy showed that DbpA was surface accessible on intact borreliae. Passive administration of DbpA antiserum protected mice from infection following challenge with heterologous B. burgdorferi sensu stricto isolates, even when serum administration was delayed for up to 4 days after challenge. DbpA is the first antigen target identified that is capable of mediating immune resolution of early, localizedB. burgdorferi infections. DbpA immunization also protected mice from B. burgdorferi challenge; DbpB immunization was much less effective. DbpA antiserum inhibited in vitro growth of manyB. burgdorferi sensu lato isolates of diverse geographic, phylogenetic, and clinical origins. In combination, these findings support a role for DbpA in the immunoprophylaxis of Lyme disease and suggest that DbpA vaccines have the potential to eliminate early-stageB. burgdorferi infections.

scholarly journals Reg4 defenses the intestine against Salmonella infection via binding the flagellin

2021 ◽  
Author(s):  
Yongtao Xiao ◽  
weipeng wang ◽  
Ying lu ◽  
xinbei tian ◽  
shanshan chen ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Bactericidal Activity ◽  
Intestinal Inflammation ◽  
Bactericidal Effect ◽  
Intestinal Epithelia ◽  
Food Borne ◽  
Negative Impacts ◽  
First Time

Salmonella Typhimurium is gram-negative flagellated bacteria that can cause food-borne gastroenteritis and diarrhea in humans and animals. The regenerating islet-derived family member 4 (Reg4) is overexpressed in the gastrointestinal tract during intestinal inflammation. However, the role of Reg4 in the intestinal inflammation induced by Salmonella Typhimurium is largely unknown. In this study, we reported for the first time that Reg4 has bactericidal activity against intestinal infection caused by Salmonella Typhimurium. In vivo, Reg4 could reduce the colonization of Salmonella Typhimurium and attenuate intestinal inflammation in the Salmonella Typhimurium-infected model. Additionally, the mice with the epithelial cell specific deletion of Reg4 (Reg4ΔIEC) exhibited more severe intestinal inflammation and more colonization of Salmonella Typhimurium. However, the administration of Reg4 could reverse these negative impacts. In vitro, Reg4 protein was showed to inhibit the growth of Salmonella Typhimurium. We further investigate the function motif of Reg4 and find that the "HDPQK" motif in Reg4 is essential to its bactericidal activity. Reg4 exerted the bactericidal effect by binding to the flagellin of Salmonella Typhimurium and suppressing its motility, adhesion, and invasion to the intestinal epithelia. In conclusion, our findings identify Reg4 as a novel antimicrobial peptide against infection by Salmonella Typhimurium and explore its possible mechanism, which may be of great significance for developing novel agents against flagellated micro pathogens.

scholarly journals The Novel β-Lactam Enhancer Zidebactam Augments theIn VivoPharmacodynamic Activity of Cefepime in a Neutropenic Mouse LungAcinetobacter baumanniiInfection Model

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
S. S. Bhagwat ◽  
H. Periasamy ◽  
S. S. Takalkar ◽  
S. R. Palwe ◽  
H. N. Khande ◽  
...  
Keyword(s):  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Mouse Lung ◽  
Infection Model ◽  
Bactericidal Action ◽  
Content Type ◽  
Time Kill ◽  
The Impact

ABSTRACTWCK 5222 is a combination of cefepime and the high-affinity PBP2-binding β-lactam enhancer zidebactam. The cefepime-zidebactam combination is active against multidrug-resistant Gram-negative bacteria, including carbapenemase-expressingAcinetobacter baumannii. The mechanism of action of the combination involves concurrent multiple penicillin binding protein inhibition, leading to the enhanced bactericidal action of cefepime. The aim of the present study was to assess the impact of the zidebactam-mediated enhancedin vitrobactericidal action in modulating the percentage of the time that the free drug concentration remains above the MIC (percentfT>MIC) for cefepime required for thein vivokilling ofA. baumannii. Cefepime and cefepime-zidebactam MICs were comparable and ranged from 2 to 16 mg/liter for theA. baumanniistrains (n = 5) employed in the study. Time-kill studies revealed the improved killing of these strains by the cefepime-zidebactam combination compared to that by the constituents alone. Employing a neutropenic mouse lung infection model, exposure-response analyses for all theA. baumanniistrains showed that the cefepimefT>MIC required for 1-log10kill was 38.9%. In the presence of a noneffective dose of zidebactam, the cefepimefT>MIC requirement dropped significantly to 15.5%, but it still rendered a 1-log10kill effect. Thus, zidebactam mediated the improvement in cefepime’s bactericidal effect observed in time-kill studies, manifestedin vivothrough the lowering of cefepime’s pharmacodynamic requirement. This is a first-ever study demonstrating a β-lactam enhancer role of zidebactam that helps augment thein vivoactivity of cefepime by reducing the magnitude of its pharmacodynamically relevant exposures againstA. baumannii.

scholarly journals Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In Vitro and In Vivo

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 633 ◽  
Author(s):  
Hari-Hara S. K. Potula ◽  
Jahanbanoo Shahryari ◽  
Mohammed Inayathullah ◽  
Andrey Victorovich Malkovskiy ◽  
Kwang-Min Kim ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Post Infection ◽  
Systemic Disease ◽  
Organ Damage ◽  
Sensu Stricto ◽  
Effector Memory ◽  
Drug Candidate

Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients are intolerant to currently available antibiotics, necessitating the development of more effective therapeutics. We previously found several drugs, including disulfiram, that exhibited effective activity against B. burgdorferi. In the current study, we evaluated the potential of repurposing the FDA-approved drug, disulfiram for its borreliacidal activity. Our results indicate disulfiram has excellent borreliacidal activity against both the log and stationary phase B. burgdorferi sensu stricto B31 MI. Treatment of mice with disulfiram eliminated the B. burgdorferi sensu stricto B31 MI completely from the hearts and urinary bladder by day 28 post infection. Moreover, disulfiram-treated mice showed reduced expressions of inflammatory markers, and thus they were protected from histopathology and cardiac organ damage. Furthermore, disulfiram-treated mice showed significantly lower amounts of total antibody titers (IgM and IgG) at day 21 and total IgG2b at day 28 post infection. FACS analysis of lymph nodes revealed a decrease in the percentage of CD19+ B cells and an increase in total percentage of CD3+ T cells, CD3+ CD4+ T helpers, and naive and effector memory cells in disulfiram-treated mice. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic for treating Lyme disease.

scholarly journals Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.

1995 ◽  
Vol 181 (1) ◽  
pp. 215-221 ◽  
Author(s):  
E Fikrig ◽  
S R Telford ◽  
R Wallich ◽  
M Chen ◽  
Y Lobet ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Classification Systems ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Natural Mode ◽  
Naturally Occurring ◽  
Vector Borne

Diversity and mutations in the genes for outer surface proteins (Osps) A and B of Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme disease, suggests that a monovalent OspA or OspB vaccine may not provide protection against antigenically variable naturally occurring B. burgdorferi. We now show that OspA or OspB immunizations protect mice from tick-borne infection with heterogeneous B. burgdorferi from different geographic regions. This result is in distinct contrast to in vitro killing analyses and in vivo protection studies using syringe injections of B. burgdorferi as the challenge inoculum. Evaluations of vaccine efficacy against Lyme disease and other vector-borne infections should use the natural mode of transmission and not be predicated on classification systems or assays that do not rely upon the vector to transmit infection.

scholarly journals THE ANTIBACTERIAL ACTIVITY OF HEMOGLOBIN

1958 ◽  
Vol 107 (2) ◽  
pp. 167-183 ◽  
Author(s):  
Derek Hobson ◽  
James G. Hirsch
Keyword(s):  
Bactericidal Activity ◽  
Lethal Effect ◽  
Bactericidal Effect ◽  
Mineral Acid ◽  
Ionic Concentration ◽  
Coliform Bacteria ◽  
Bactericidal Action ◽  
Lethal Action ◽  
Serum Fractions

Low concentrations of hemoglobin (0.1 µg./ml. or less) exert a lethal action on some Gram-negative bacteria under certain conditions in vitro. Hemoglobins from various mammals and the distinct genetic types of human hemoglobin all manifest similar bactericidal activity. The bactericidal effect is a function of the globin moiety of the molecule; native and acid or acid-alcohol denatured globins have the same degree of activity. Hemoglobins kill enterobacteriaceae only under precisely controlled conditions. The test medium must be low in ionic concentration and acid in reaction. Various strains of Escherichia and Salmonella are susceptible to the lethal effect of hemoglobin, while the few strains of Shigella, Klebsiella, and Proteus examined were resistant. Certain acid polysaccharides and basic amines or proteins block the bactericidal effect when incorporated in the test in low concentration. Present evidence also suggests that exposure of the microorganisms to certain cations such as magnesium renders them resistant to the lethal action of globin. Hemoglobin loses its bactericidal power when complexed with haptoglobin, and serum fractions rich in free haptoglobin protect otherwise susceptible bacteria from killing by hemoglobin. The reaction appears to be a bactericidal rather than a bacteriostatic one. At 38°C. maximal killing requires approximately 30 minutes; at temperatures of 28°C. or 0°C. the bactericidal action does not take place. The minimal concentration of hemoglobin required to kill 50 per cent of the microorganisms in the test is unrelated to the size of the bacterial inoculum. Under conditions suitable for bactericidal action, hemoglobin is adsorbed onto heat-killed susceptible strains of coliform bacteria; material possessing bactericidal activity can be eluted with dilute mineral acid.

Improvement of effectiveness in maize breeding

2006 ◽  
Vol 54 (3) ◽  
pp. 351-358 ◽  
Author(s):  
P. Pepó
Keyword(s):  
Recurrent Selection ◽  
Genetic Manipulation ◽  
Field Testing ◽  
Tissue Cultures ◽  
Maize Breeding ◽  
Breeding Programmes ◽  
Speed Up ◽  
Selection For

Plant regeneration via tissue culture is becoming increasingly more common in monocots such as maize (Zea mays L.). Pollen (gametophytic) selection for resistance to aflatoxin in maize can greatly facilitate recurrent selection and the screening of germplasm for resistance at much less cost and in a shorter time than field testing. In vivo and in vitro techniques have been integrated in maize breeding programmes to obtain desirable agronomic attributes, enhance the genes responsible for them and speed up the breeding process. The efficiency of anther and tissue cultures in maize and wheat has reached the stage where they can be used in breeding programmes to some extent and many new cultivars produced by genetic manipulation have now reached the market.

scholarly journals Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bactericidal Activity ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Bacterial Killing ◽  
Blood Neutrophils ◽  
Vitro Model

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.

scholarly journals ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Ørjan Samuelsen ◽  
Ove Alexander Høgmoen Åstrand ◽  
Christopher Fröhlich ◽  
Adam Heikal ◽  
Susann Skagseth ◽  
...  
Keyword(s):  
Active Site ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Functional Space ◽  
Bactericidal Effect ◽  
Gram Negative ◽  
Content Type

ABSTRACT Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ∼30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.

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