Establishment of a new murine model of liver abscess induced by Fusobacterium necrophorum injected into the caudal vein

Anaerobic bacterial infection is often accompanied by abscess formation; however, few in vivo studies have been published with descriptive data specifically evaluating antimicrobial activity in the presence of abscesses. The aim of this study was to establish a murine model of anaerobic infection with abscess formation and to verify the utility of this model for evaluating the in vivo efficacy of an antimicrobial agent. A clinical isolate of Fusobacterium necrophorum was inoculated into the caudal vein of immunocompetent BALB/c mice at 108 c.f.u. per mouse. Changes in body weight, bacterial load and histopathology of key organs were evaluated. After inoculation, bacterial counts in the liver increased from 104 to 108 c.f.u. after 1–3 days, and liver abscess formation was observed on the day following infection. Abscess formation and bacterial growth were not observed in other organs. In this model, 3 days of treatment with 5 mg metronidazole kg−1 eradicated F. necrophorum in the liver; however, a reduction in bacterial load was not observed with 0.05 mg metronidazole kg−1. In this study, we established a novel murine model of F. necrophorum liver abscess via haematogenous infection that may be useful for investigating in vivo antimicrobial activity against anaerobic abscesses and understanding the pathogenesis of F. necrophorum infection.

Download Full-text

A Novel Qualitative and Quantitative Biofilm Assay Based on 3D Soft Tissue

International Journal of Biomaterials ◽

10.1155/2014/768136 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 11

Author(s):

Bodil Hakonen ◽

Linnea K. Lönnberg ◽

Eva Larkö ◽

Kristina Blom

Keyword(s):

Antimicrobial Activity ◽

Soft Tissues ◽

Bacterial Load ◽

Wound Dressings ◽

Rapid Screening ◽

Qualitative And Quantitative ◽

Development Of Resistance ◽

Novel Method

The lack of predictablein vitromethods to analyze antimicrobial activity could play a role in the development of resistance to antibiotics. Current used methods analyze planktonic cells but for the method to be clinically relevant, biofilm inin vivolike conditions ought to be studied. Hence, our group has developed a qualitative and quantitative method within vivolike 3D tissue for prediction of antimicrobial activity in reality. Devices (wound dressings) were applied on top ofPseudomonas aeruginosainoculated Muller-Hinton (MH) agar or 3D synthetic soft tissues (SST) and incubated for 24 hours. The antibacterial activity was then analyzed visually and by viable counts. On MH agar two out of three silver containing devices showed zone of inhibitions (ZOI) and on SST, ZOI were detected for all three. Corroborating results were found upon evaluating the bacterial load in SST and shown to be silver concentration dependent. In conclusion, a novel method was developed combining visual rapid screening and quantitative evaluation of the antimicrobial activity in both tissue and devices. It uses tissue allowing biofilm formation thus mimicking reality closely. These conditions are essential in order to predict antimicrobial activity of medical devices in the task to prevent device related infections.

Download Full-text

In vitro and in vivo antibacterial activity assays of carvacrol: A candidate for development of innovative treatments against KPC-producing Klebsiella pneumoniae

PLoS ONE ◽

10.1371/journal.pone.0246003 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0246003

Author(s):

Gleyce Hellen de Almeida de Souza ◽

Joyce Alencar dos Santos Radai ◽

Marcia Soares Mattos Vaz ◽

Kesia Esther da Silva ◽

Thiago Leite Fraga ◽

...

Keyword(s):

Antimicrobial Activity ◽

Klebsiella Pneumoniae ◽

Bacterial Load ◽

Antimicrobial Effect ◽

Multidrug Resistant ◽

Bacterial Cells ◽

Carbapenem Resistant ◽

Interesting Candidate

Dissemination of carbapenem-resistant Klebsiella pneumoniae poses a threat to the successful treatment of bacterial diseases and increases the need for new antibacterial agents development. The objective of this study was to determine the antimicrobial activity of carvacrol against multidrug-resistant K. pneumoniae. Carbapenemase production was detected by MALDI-TOF. The PCR and sequencing showed that the blaKPC-2, blaOXA-48, blaNDM-1, blaCTX-M-8 genes were present in carbapenem-resistant K. pneumoniae strains. The polymyxin-resistant K. pneumoniae strain exhibited alterations in mgrB gene. The antimicrobial activity of carvacrol was evaluated in vitro using broth microdilution and time-kill methods. For this, carbapenem-resistant K. pneumoniae and polymyxin-resistant strains, were evaluated. The in vitro results showed that carvacrol had antimicrobial activity against all isolates evaluated. The survival curves showed that carvacrol eradicated all of the bacterial cells within 4 h. The antimicrobial effect of carvacrol in vivo was determined using a mouse model of infection with Klebsiella pneumoniae carbapenemase (KPC). The treatment with carvacrol was associated with increased survival, and significantly reduced bacterial load in peritoneal lavage. In addition, groups treated with carvacrol, had a significant reduction in the total numbers of white cell and significantly increased of platelets when compared to the untreated group. In vivo and in vitro studies showed that carvacrol regimens exhibited significant antimicrobial activity against KPC-producing K. pneumoniae, making it an interesting candidate for development of alternative treatments.

Download Full-text

Efficacy of ceftolozane in a murine model of Pseudomonas aeruginosa acute pneumonia: in vivo antimicrobial activity and impact on host inflammatory response

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dks343 ◽

2012 ◽

Vol 68 (1) ◽

pp. 177-183 ◽

Cited By ~ 19

Author(s):

C. Jacqueline ◽

A. Roquilly ◽

C. Desessard ◽

D. Boutoille ◽

A. Broquet ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Inflammatory Response ◽

Murine Model ◽

Acute Pneumonia ◽

Host Inflammatory Response

Download Full-text

Effects of the components of Fusobacterium necrophorum in experimental liver abscess formation in mice.

The Japanese Journal of Veterinary Science ◽

10.1292/jvms1939.47.589 ◽

1985 ◽

Vol 47 (4) ◽

pp. 589-595 ◽

Cited By ~ 5

Author(s):

Yasuyuki NAKAJIMA ◽

Kikuyasu NAKAMURA ◽

Shotaro TAKEUCHI

Keyword(s):

Liver Abscess ◽

Fusobacterium Necrophorum ◽

Abscess Formation ◽

Experimental Liver

Download Full-text

Fusobacterium necrophorum infection in mice as a model for the study of liver abscess formation and induction of immunity.

Infection and Immunity ◽

10.1128/iai.13.5.1473-1478.1976 ◽

1976 ◽

Vol 13 (5) ◽

pp. 1473-1478 ◽

Cited By ~ 16

Author(s):

P M Abe ◽

E S Lennard ◽

J W Holland

Keyword(s):

Liver Abscess ◽

Fusobacterium Necrophorum ◽

Abscess Formation

Download Full-text

Experimental Phage Therapy against Staphylococcus aureus in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01513-06 ◽

2007 ◽

Vol 51 (8) ◽

pp. 2765-2773 ◽

Cited By ~ 165

Author(s):

Rosanna Capparelli ◽

Marianna Parlato ◽

Giorgia Borriello ◽

Paola Salvatore ◽

Domenico Iannelli

Keyword(s):

Staphylococcus Aureus ◽

Phage Therapy ◽

Bacterial Load ◽

Abscess Formation ◽

Methicillin Resistant ◽

Potential Use

ABSTRACT The present study describes a bacteriophage (MSa) active against Staphylococcus aureus, including methicillin-resistant staphylococcal strains. When inoculated into mice simultaneously with S. aureus A170 (108 CFU/mouse), phage (109 PFU) rescued 97% of the mice; when applied to nonlethal (5 × 106 CFU/mouse) 10-day infections, the phage also fully cleared the bacteria. The phage MSa, delivered inside macrophages by S. aureus, kills the intracellular staphylococci in vivo and in vitro. The phage can also prevent abscess formation and reduce the bacterial load and weight of abscesses. These results suggest a potential use of the phage for the control of both local and systemic human S. aureus infections.

Download Full-text

Antimicrobial Activity of Murine Lung Cells against Staphylococcus aureus Is Increased In Vitro and In Vivo after Elafin Gene Transfer

Infection and Immunity ◽

10.1128/iai.73.6.3609-3617.2005 ◽

2005 ◽

Vol 73 (6) ◽

pp. 3609-3617 ◽

Cited By ~ 30

Author(s):

J. W. McMichael ◽

A. I. Maxwell ◽

K. Hayashi ◽

K. Taylor ◽

W. A. Wallace ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Gene Transfer ◽

Core Protein ◽

Bacterial Load ◽

Intratracheal Instillation ◽

Respiratory Pathogen ◽

Tracheal Epithelial Cells

ABSTRACT Staphylococcus aureus is a pathogen often found in pneumonia and sepsis. In the context of the resistance of this organism to conventional antibiotics, an understanding of the regulation of natural endogenous antimicrobial molecules is of paramount importance. Previous studies have shown that both human and mouse airways express a variety of these molecules, including defensins, cathelicidins, and the four-disulfide core protein secretory leukocyte protease inhibitor. We demonstrate here by culturing mouse tracheal epithelial cells at an air-liquid interface that, despite the production of Defb1, Defb14, and Defr1 in this system, these cells are unable to clear S. aureus when exposed to this respiratory pathogen. Using an adenovirus (Ad)-mediated gene transfer strategy, we show that overexpression of elafin, an anti-elastase/antimicrobial molecule (also a member of the four-disulfide core protein family), dramatically improves the clearance of S. aureus. In addition, we also demonstrate that this overexpression is efficient in vivo and that intratracheal instillation of Ad-elafin significantly reduced the lung bacterial load and demonstrates concomitant anti-inflammatory activity by reducing neutrophil numbers and markers of lung inflammation, such as bronchoalveolar lavage levels of tumor necrosis factor and myeloperoxidase. These findings show that an increased antimicrobial activity phenotype is provided by the elafin molecule and have implications for its use in S. aureus-associated local and systemic infections.

Download Full-text

In VitroandIn VivoActivities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02823-14 ◽

2014 ◽

Vol 58 (9) ◽

pp. 5342-5349 ◽

Cited By ~ 37

Author(s):

Xiaozhe Wu ◽

Zhenling Wang ◽

Xiaolu Li ◽

Yingzi Fan ◽

Gu He ◽

...

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Antimicrobial Peptides ◽

Bacterial Load ◽

Prediction Method ◽

Multidrug Resistant ◽

Antimicrobial Activities ◽

Bacterial Strains ◽

Content Type

ABSTRACTTo design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. Thein vivoantimicrobial activity of DP7 was tested in aStaphylococcus aureusinfection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of theS. aureusouter membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.

Download Full-text