scholarly journals In Vivo Growth of Pseudomonas aeruginosa Strains PAO1 and PA14 and the Hypervirulent Strain LESB58 in a Rat Model of Chronic Lung Infection

2007 ◽  
Vol 190 (8) ◽  
pp. 2804-2813 ◽  
Author(s):  
Irena Kukavica-Ibrulj ◽  
Alessandra Bragonzi ◽  
Moira Paroni ◽  
Craig Winstanley ◽  
François Sanschagrin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Rat Model ◽  
Growth Curves ◽  
Lung Infection ◽  
In Vitro Assays ◽  
Bacterial Strains ◽  
In Vivo Growth ◽  
Chronic Lung Infection

ABSTRACT Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality in cystic fibrosis (CF) patients. The P. aeruginosa strains PAO1 and PA14 were compared with the Liverpool epidemic strain LESB58 to assess in vivo growth, infection kinetics, and bacterial persistence and localization within tissues in a rat model of chronic lung infection. The three P. aeruginosa strains demonstrated similar growth curves in vivo but differences in tissue distribution. The LESB58 strain persisted in the bronchial lumen, while the PAO1 and PA14 strains were found localized in the alveolar regions and grew as macrocolonies after day 7 postinfection. Bacterial strains were compared for swimming and twitching motility and for the production of biofilm. The P. aeruginosa LESB58 strain produced more biofilm than PAO1 and PA14. Competitive index (CI) analysis of PAO1, PA14, and LESB58 in vivo indicated CI values of 0.002, 0.0002, and 0.14 between PAO1-PA14, PAO1-LESB58, and LESB58-PA14, respectively. CI analysis comparing the in vivo growth of the PAO1 ΔPA5441 mutant and four PA14 surface attachment-defective (sad) mutants gave CI values 10 to 1,000 times lower in competitions with their respective wild-type strains PAO1 and PA14. P. aeruginosa strains studied in the rat model of chronic lung infection demonstrated similar in vivo growth but differences in virulence as shown with a competitive in vivo assay. These differences were further confirmed with biofilm and motility in vitro assays, where strain LESB58 produced more biofilm but had less capacity for motility than PAO1 and PA14.

scholarly journals Bactericidal/Permeability-Increasing Protein Preeminently Mediates Clearance of Pseudomonas aeruginosa In Vivo via CD18-Dependent Phagocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jomkuan Theprungsirikul ◽  
Sladjana Skopelja-Gardner ◽  
Ashley S. Burns ◽  
Rachel M. Wierzbicki ◽  
William F. C. Rigby
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critical Role ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Opsonic Activity ◽  
Obstructive Pulmonary Disease ◽  
Neutrophil Dysfunction ◽  
Chronic Lung Infection

Chronic Pseudomonas aeruginosa infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in in vivo immunity against P. aeruginosa. Wild type and BPI-deficient (Bpi-/-) mice were infected with P. aeruginosa, and bacterial clearance, cell infiltrates, cytokine production, and in vivo phagocytosis were quantified. Bpi-/- mice exhibited a decreased ability to clear P. aeruginosa in vivo in concert with increased neutrophil counts and cytokine release. Bpi-/- neutrophils displayed decreased phagocytosis that was corrected by exogenous BPI in vitro. Exogenous BPI also enhanced clearance of P. aeruginosa in Bpi-/- mice in vivo by increasing P. aeruginosa uptake by neutrophils in a CD18-dependent manner. These data indicate that BPI plays an essential role in innate immunity against P. aeruginosa through its opsonic activity and suggest that perturbations in BPI levels or function may contribute to chronic lung infection with P. aeruginosa.

scholarly journals Microbial Growth Inhibition by Alternating Electric Fields in Mice with Pseudomonas aeruginosa Lung Infection

2010 ◽  
Vol 54 (8) ◽  
pp. 3212-3218 ◽  
Author(s):  
Moshe Giladi ◽  
Yaara Porat ◽  
Alexandra Blatt ◽  
Esther Shmueli ◽  
Yoram Wasserman ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Growth Inhibition ◽  
Electric Fields ◽  
Bacterial Growth ◽  
Lung Infection ◽  
Alternating Electric Fields ◽  
Microbial Growth Inhibition ◽  
Bacterial Growth Inhibition

ABSTRACT High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2°C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality.

scholarly journals Lactococcosis a Re-Emerging Disease in Aquaculture: Disease Significant and Phytotherapy

2021 ◽  
Vol 8 (9) ◽  
pp. 181
Author(s):  
Mehdi Soltani ◽  
Bernardo Baldisserotto ◽  
Seyed Pezhman Hosseini Shekarabi ◽  
Shafigh Shafiei ◽  
Masoumeh Bashiri
Keyword(s):  
Antibacterial Activity ◽  
Essential Oils ◽  
Medicinal Herbs ◽  
In Vitro Assays ◽  
Bacterial Disease ◽  
Bacterial Strains ◽  
Immune Parameters ◽  
Aquaculture Industry

Lactococcosis, particularly that caused by Lactococcus garvieae, is a major re-emerging bacterial disease seriously affecting the sustainability of aquaculture industry. Medicinal herbs and plants do not have very much in vitro antagonism and in vivo disease resistance towards lactococcosis agents in aquaculture. Most in vitro studies with herbal extractives were performed against L. garvieae with no strong antibacterial activity, but essential oils, especially those that contain thymol or carvacrol, are more effective. The differences exhibited by the bacteriostatic and bactericidal functions for a specific extractive in different studies could be due to different bacterial strains or parts of chemotypes of the same plant. Despite essential oils being shown to have the best anti-L. garvieae activity in in vitro assays, the in vivo bioassays required further study. The extracts tested under in vivo conditions presented moderate efficacy, causing a decrease in mortality in infected animals, probably because they improved immune parameters before challenging tests. This review addressed the efficacy of medicinal herbs to lactococcosis and discussed the presented gaps.

scholarly journals 1066. In Vitro and in Vivo Antimicrobial Activity of Cefiderocol and Comparators against Achromobacter spp

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S625-S626
Author(s):  
Ryuichiro Nakai ◽  
Ayaka makino ◽  
Hitomi Hama ◽  
Toriko Yoshitomi ◽  
Rio Nakamura ◽  
...  
Keyword(s):  
Rat Model ◽  
Murine Model ◽  
Lung Infection ◽  
Vitro Activity ◽  
Infection Model ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
In Vivo Efficacy

Abstract Background Achromobacter spp. is intrinsically resistant to multiple antibiotics, and the treatment options are limited. Cefiderocol (CFDC), a siderophore cephalosporin approved in US and EU, is active against a wide variety of aerobic Gram-negative bacteria, including carbapenem-resistant strains. In this study, in vitro and in vivo antibacterial activity of CFDC against Achromobacter spp. was evaluated. Methods A total of 334 global isolates collected by IHMA from 39 countries in 2015-2019 were used. Minimum inhibitory concentrations (MICs) of CFDC and comparators were determined by broth microdilution method using iron-depleted CAMHB or CAMHB, respectively, as recommended by CLSI guidelines. In vivo efficacy of CFDC was compared with meropenem (MEM), piperacillin-tazobactam (PIP/TAZ), ceftazidime (CAZ), and ciprofloxacin (CIP) in a neutropenic murine lung infection model (n=5), and compared with MEM in a immunocompetent rat lung infection model (n=3-7) caused by 2 A. xylosoxydans. In the murine model, treatment was given 2, 5, and 8 hours post-infection, and the numbers of viable cfu in lungs were determined 24 hours post-infection. In the rat model, the humanized PK in plasma resulting from CFDC 2 g every 8 h (3-h infusion) or meropenem 1 g every 8 h (0.5-h infusion) were recreated via continuous intravenous infusion for 4 days, following which cfu in lungs were determined. Results CFDC showed in vitro activity with MIC50/90 of 0.06/0.5 µg/mL against 334 Achromobacter spp. Only 7 isolates (2.1%) had MICs > 4 µg/mL. These were the lowest values among all compound tested (Table). In the murine model, CFDC caused > 1.5 log10 decrease of viable cfu in lungs at 100 mg/kg dose (%fT >MIC: < 50%) from baseline control against both of strains (CFDC MIC: 0.5 and 2 µg/mL) (P< 0.05). No decrease of cfu in lungs was observed for the comparators at 100 mg/kg (MEM, PIP/TAZ, CAZ, and CIP MICs were >16, >64, >32, and >8 µg/mL, respectively). In the rat model, humanized CFDC dosing reduced the viable cfu by >1 log10 CFU/lung compared with baseline controls (P< 0.05). MEM showed no significant activity. In vitro activity of CFDC and comparator agents against Achromobacter spp. 334 Achromobacter spp. isolates collected from 2015 and 2019. The majority of isolates tested were A. xylosoxidans (312/334; 93.4%), followed by A. insolitus (11/334; 3.3%), Achromobacter sp. (8/334; 2.4%), A. denitrificans (2/334; 0.6%), and A. piechaudii (1/334; 0.3%). Conclusion CFDC showed potent in vivo efficacy reflecting in vitro activity against A. xylosoxidans. The results suggested that CFDC has the potential to be an effective therapeutic option for Achromobacter spp. infections. Disclosures Ryuichiro Nakai, MSc, Shionogi TechnoAdvance Research & Co., Ltd. (Employee) Ayaka makino, BSc, Shionogi TechnoAdvance Research & Co., Ltd. (Employee) Toriko Yoshitomi, -, Shionogi TechnoAdvance Research & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi TechnoAdvance Research & Co., Ltd. (Employee) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Yoshinori Yamano, PhD, Shionogi (Employee)

scholarly journals Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme

2021 ◽  
Vol 12 ◽  
Author(s):  
Chendi Jing ◽  
Chenghua Liu ◽  
Yu Liu ◽  
Ruli Feng ◽  
Run Cao ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Alkaline Protease ◽  
Chronic Infection ◽  
Active Sites ◽  
Neutrophil Extracellular Traps ◽  
Lung Infection ◽  
Bacterial Burden ◽  
Extracellular Traps

Extracellular traps released by neutrophils (NETs) are essential for the clearance of Pseudomonas aeruginosa. Alkaline protease (AprA) secreted by P. aeruginosa negatively correlates with clinical improvement. Moreover, anti-AprA in patients with cystic fibrosis (CF) can help identify patients with aggressive forms of chronic infection. However, the mechanism underlying the clinical outcomes remains unclear. We demonstrated that aprA deficiency in P. aeruginosa decreased the bacterial burden and reduced lung infection. AprA degraded NET components in vitro and in vivo but did not affect NET formation. Importantly, antibodies induced by AprA acted as an agonist and directly enhanced the degrading activities of AprA. Moreover, antisera from patients with P. aeruginosa infection exhibited antibody-dependent enhancement (ADE) similar to that of the antibodies we prepared. Our further investigations showed that the interaction between AprA and the specific antibodies might make the enzyme active sites better exposed, and subsequently enhance the recognition of substrates and accelerate the degradation. Our findings revealed that AprA secreted by P. aeruginosa may aggravate infection by destroying formed NETs, an effect that was further enhanced by its antibodies.

scholarly journals Synergistic Activity of Berberine with Azithromycin against Pseudomonas Aeruginosa Isolated from Patients with Cystic Fibrosis of Lung In Vitro and In Vivo

2017 ◽  
Vol 42 (4) ◽  
pp. 1657-1669 ◽  
Author(s):  
YongTao Li ◽  
JianRong Huang ◽  
LanJuan Li ◽  
LinSheng Liu
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Infection ◽  
Extracellular Dna ◽  
Pcr Analysis ◽  
Infection Model ◽  
Synergistic Activity ◽  
Time Kill

Background/Aims: Pseudomonas aeruginosa (PA) is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF). The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics. Methods: The antimicrobial effects of azithromycin (AZM) and berberine (BER) alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines. Results: AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM) at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS) molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER. Conclusion: BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo.

scholarly journals Antibody response to Pseudomonas aeruginosa surface protein antigens in a rat model of chronic lung infection

1988 ◽  
Vol 27 (4) ◽  
pp. 255-261 ◽  
Author(s):  
D. M. G. Cochrane ◽  
M. R. W. Brown ◽  
H. Anwar ◽  
P. H. Weller ◽  
K. Lam ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibody Response ◽  
Rat Model ◽  
Surface Protein ◽  
Lung Infection ◽  
Protein Antigens ◽  
Chronic Lung Infection

scholarly journals Novel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa Infection

2021 ◽  
Author(s):  
Feng Chen ◽  
Xingjun Cheng ◽  
Jianbo Li ◽  
Xiefang Yuan ◽  
Xiuhua Huang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mouse Models ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Inflammatory Responses ◽  
Multi Drug Resistance ◽  
Bacterial Strains ◽  
Genetic Traits

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

scholarly journals In vitro Assessment of Bacterial Strains Associated with Microalgae as Potential Probiotics

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Aimi Zabidi ◽  
Natasya-Ain Rosland ◽  
Jasmin Yaminudin ◽  
Murni Karim
Keyword(s):  
Antimicrobial Activity ◽  
In Vitro Assays ◽  
Disc Diffusion ◽  
Bacterial Strains ◽  
Pathogenic Vibrio ◽  
Fish And Shellfish ◽  
Diffusion Assay ◽  
Vibrio Spp

Bacteria and microalgae are essential elements in the aquatic ecosystem, co-existing and having constant interactions with each other which help microalgae to exert its beneficial effect as probiotics in aquaculture. This research aims to isolate and identify potential probiotics from different species of microalgae and to evaluate their antimicrobial activity against pathogenic Vibrio spp. via series of in vitro assays; disc diffusion, well diffusion, and co-culture assays. A total of 18 bacterial strains were isolated from five species of microalgae; Chlorella sp., Nannochloropsis sp., Amphora sp., Chaetoceros sp., and Spirulina sp.. The isolated strains were tested in in vitro antagonistic assay against four Vibrio spp. (Vibrio harveyi, Vibrio alginolyticus, Vibrio vulnificus, and Vibrio parahaemolyticus). Seventeen strains demonstrated antimicrobial activity with the highest inhibition was observed by strain SPS11 against V. parahaemolyticus (12.6 ± 0.36 mm) in disc diffusion assay and strain NAS32 showed 13.2 ± 0.45 mm clear zone against V. vulnificus in well diffusion assay. In co-culture assay, both the SPS11 and NAS32 were able to reduce the growth of V. parahaemolyticus and V. harveyi at concentration of 106 and 108 CFU mL-1, respectively. Strains SPS11 and NAS32 were characterized as gram positive bacteria with rod shape and further identified as Lysinibacillus fusiformis (SPS11) and Lysinibacillus sphaericus (NAS32) using 16s rRNA. These two strains should be further studied in in vivo challenged experiments in fish and shellfish to explore their probiotic effects.

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