scholarly journals Isolation, Genomic Analysis, and Preliminary Application of a Bovine Klebsiella pneumoniae Bacteriophage vB_Kpn_B01

2021 ◽  
Vol 8 ◽  
Author(s):  
Zidan Luo ◽  
Shangjingchao Geng ◽  
Biao Lu ◽  
Guangli Han ◽  
Yin Wang ◽  
...  
Keyword(s):  
Treatment Group ◽  
Klebsiella Pneumoniae ◽  
Bacterial Load ◽  
Dairy Farm ◽  
Genomic Analysis ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Bacterial Group ◽  
Entire Genome

Klebsiella pneumoniae is an important pathogen that can infect both humans and cattle. The widespread K. pneumoniae and its high drug resistance make it difficult to treat Klebsiella infections/diseases. In this study, a lytic K. pneumoniae bacteriophage vB_Kpn_B01 was isolated from a dairy farm trough in Sichuan Province, and its biological properties were studied, and the entire genome of vB_Kpn_B01 was sequenced. The therapeutic effects of the phage on disease-causing mice were preliminarily tested. Phages found in this study are double-stranded DNA bacterial viruses belonging to the family Siphoviridae, Sugarlandvirus. The results suggest that vB_Kpn_B01 has strong specificity and low adaptability to different adverse conditions. Meanwhile, the predicted gene products of phage vB_Kpn_B01 comprised 149 coding sequences (CDS) and 25 tRNAs, of which 34 CDS had known functions. Of course, vB_Kpn_B01 did not contain any known antibiotic-resistant or virulent genes. The pathological sections of the liver and lungs of mice showed that the inflammatory scores of the treatment group were lower than in the bacterial group. Phage vB_Kpn_B01 alleviated the inflammatory response in the organs of the infected mice, and the organ tissue bacterial load of the treatment group was significantly lower than that of the bacterial group. Therefore, vB_Kpn_B01 can inhibit the proliferation of K. pneumoniae 18 in vivo and can alleviate the inflammation of target organs caused by infectious bacteria, which preliminarily indicates that vB_Kpn_B01 has a certain therapeutic effect on laboratory-infected mice.

scholarly journals Safety and Efficacy of a Phage, kpssk3, in an in vivo Model of Carbapenem-Resistant Hypermucoviscous Klebsiella pneumoniae Bacteremia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunlong Shi ◽  
Yuan Peng ◽  
Yixin Zhang ◽  
Yu Chen ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Gut Microbiota ◽  
Mammalian Cells ◽  
Phage Therapy ◽  
In Vivo Model ◽  
Therapeutic Effects ◽  
Global Public Health ◽  
Carbapenem Resistant

Antimicrobial resistance (AMR) is one of the most significant threats to global public health. As antibiotic failure is increasing, phages are gradually becoming important agents in the post-antibiotic era. In this study, the therapeutic effects and safety of kpssk3, a previously isolated phage infecting carbapenem-resistant hypermucoviscous Klebsiella pneumoniae (CR-HMKP), were evaluated in a mouse model of systemic CR-HMKP infection. The therapeutic efficacy experiment showed that intraperitoneal injection with a single dose of phage kpssk3 (1 × 107 PFU/mouse) 3 h post infection protected 100% of BALB/c mice against bacteremia induced by intraperitoneal challenge with a 2 × LD100 dose of NY03, a CR-HMKP clinical isolate. In addition, mice were treated with antibiotics from three classes (polymyxin B, tigecycline, and ceftazidime/avibactam plus aztreonam), and the 7 days survival rates of the treated mice were 20, 20, and 90%, respectively. The safety test consisted of 2 parts: determining the cytotoxicity of kpssk3 and evaluating the short- and long-term impacts of phage therapy on the mouse gut microbiota. Phage kpssk3 was shown to not be cytotoxic to mammalian cells in vitro or in vivo. Fecal samples were collected from the phage-treated mice at 3 time points before (0 day) and after (3 and 10 days) phage therapy to study the change in the gut microbiome via high-throughput 16S rDNA sequence analysis, which revealed no notable alterations in the gut microbiota except for decreases in the Chao1 and ACE indexes.

scholarly journals ANTI-TUMOR EFFECT OF CPDA ENANTIOMERS IN VITRO IN THE MODEL OF ACUTE LYMPHOBLASTIC LEUKEMIA

2017 ◽  
Vol 16 (1) ◽  
pp. 61-69
Author(s):  
A. V. Savinkova ◽  
L. R. Tilova ◽  
O. I. Borisova ◽  
E. M. Zhidkova ◽  
K. A. Kuzin ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Lymphoblastic Leukemia ◽  
Biological Properties ◽  
Pcr Analysis ◽  
Therapeutic Effects ◽  
Blood Cancer ◽  
Apoptotic Effects ◽  
Anti Tumor Activity

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.

scholarly journals Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Functional Changes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Katarzyna Drela ◽  
Luiza Stanaszek ◽  
Adam Nowakowski ◽  
Zuzanna Kuczynska ◽  
Barbara Lukomska
Keyword(s):  
Stem Cell ◽  
Negative Impact ◽  
Ex Vivo ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Functional Changes ◽  
Cell Propagation ◽  
Ex Vivo Culture

Mesenchymal stem cells (MSCs) are attractive candidates for cell-based tissue repair approaches. Hundreds of clinical trials using MSCs have been completed and many others are still being investigated. For most therapeutic applications, MSC propagation in vitro is often required. However, ex vivo culture condition is not fully physiological and may affect biological properties of MSCs including their regenerative potential. Moreover, both cell cryopreservation and labelling procedure prior to infusion may have the negative impact on their expected effect in vivo. The incidence of MSC transformation during in vitro culture should be also taken into consideration before using cells in stem cell therapy. In our review, we focused on different aspects of MSC propagation that might influence their regenerative properties of MSC. We also discussed the influence of different factors that might abolish MSC proliferation and differentiation as well as potential impact of stem cell senescence and aging. Despite of many positive therapeutic effects of MSC therapy, one has to be conscious about potential cell changes that could appear during manufacturing of MSCs.

scholarly journals Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aye Mya Sithu Shein ◽  
Dhammika Leshan Wannigama ◽  
Paul G. Higgins ◽  
Cameron Hurst ◽  
Shuichi Abe ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Load ◽  
In Vivo Studies ◽  
Adaptive Responses ◽  
Colistin Resistance ◽  
Internal Organs ◽  
Vascular Catheters ◽  
Hostile Environments

AbstractDevelopment of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25–1 µg/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.

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

PLoS ONE ◽  
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.

scholarly journals Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingjie Song ◽  
Xianggui Yang ◽  
Jinwei Huang ◽  
Xiaokui Zhu ◽  
Guohui Han ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Resistant Bacteria ◽  
Comparative Genomic ◽  
Wild Type ◽  
Bacteriophage Therapy ◽  
Deletion Mutations ◽  
Invasive Infections

Hypervirulent Klebsiella pneumoniae (hvKp), one of the major community-acquired pathogens, can cause invasive infections such as liver abscess. In recent years, bacteriophages have been used in the treatment of K. pneumoniae, but the characteristics of the phage-resistant bacteria produced in the process of phage therapy need to be evaluated. In this study, two Podoviridae phages, hvKpP1 and hvKpP2, were isolated and characterized. In vitro and in vivo experiments demonstrated that the virulence of the resistant bacteria was significantly reduced compared with that of the wild type. Comparative genomic analysis of monoclonal sequencing showed that nucleotide deletion mutations of wzc and wcaJ genes led to phage resistance, and the electron microscopy and mucoviscosity results showed that mutations led to the loss of the capsule. Meanwhile, animal assay indicated that loss of capsule reduced the virulence of hvKp. These findings contribute to a better understanding of bacteriophage therapy, which not only can kill bacteria directly but also can reduce the virulence of bacteria by phage screening.

scholarly journals Colonization and immune modulation properties of Klebsiella pneumoniae biofilm-dispersed cells

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Cyril Guilhen ◽  
Sylvie Miquel ◽  
Nicolas Charbonnel ◽  
Laura Joseph ◽  
Guillaume Carrier ◽  
...  
Keyword(s):  
Immune Response ◽  
Klebsiella Pneumoniae ◽  
Immune Modulation ◽  
Bacterial Load ◽  
Phenotypic Properties ◽  
Planktonic Bacteria ◽  
Initial Adhesion ◽  
Sessile Cells ◽  
Dispersed Cells

Abstract Biofilm-dispersal is a key determinant for further dissemination of biofilm-embedded bacteria. Recent evidence indicates that biofilm-dispersed bacteria have transcriptional features different from those of both biofilm and planktonic bacteria. In this study, the in vitro and in vivo phenotypic properties of Klebsiella pneumoniae cells spontaneously dispersed from biofilm were compared with those of planktonic and sessile cells. Biofilm-dispersed cells, whose growth rate was the same as that of exponential planktonic bacteria but significantly higher than those of sessile and stationary planktonic forms, colonized both abiotic and biotic surfaces more efficiently than their planktonic counterparts regardless of their initial adhesion capabilities. Microscopy studies suggested that dispersed bacteria initiate formation of microcolonies more rapidly than planktonic bacteria. In addition, dispersed cells have both a higher engulfment rate and better survival/multiplication inside macrophages than planktonic cells and sessile cells. In an in vivo murine pneumonia model, the bacterial load in mice lungs infected with biofilm-dispersed bacteria was similar at 6, 24 and 48 h after infection to that of mice lungs infected with planktonic or sessile bacteria. However, biofilm-dispersed and sessile bacteria trend to elicit innate immune response in lungs to a lesser extent than planktonic bacteria. Collectively, the findings from this study suggest that the greater ability of K. pneumoniae biofilm-dispersed cells to efficiently achieve surface colonization and to subvert the host immune response confers them substantial advantages in the first steps of the infection process over planktonic bacteria.

scholarly journals Glycomacropeptide Bioactivity and Health: A Review Highlighting Action Mechanisms and Signaling Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 598 ◽  
Author(s):  
Laura Córdova-Dávalos ◽  
Mariela Jiménez ◽  
Eva Salinas
Keyword(s):  
Signaling Pathways ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Biological Properties ◽  
Therapeutic Effects ◽  
Action Mechanisms ◽  
Comprehensive Compilation

Food-derived bioactive peptides are reported as beneficial and safe for human health. Glycomacropeptide (GMP) is a milk-protein-derived peptide that, in addition to its nutritional value, retains many biological properties and has therapeutic effects in several inflammatory disorders. GMP was shown under in vitro and in vivo conditions to exert a number of activities that regulate the physiology of important body systems, namely the gastrointestinal, endocrine, and immune systems. This review represents a comprehensive compilation summarizing the current knowledge and updated information on the major biological properties associated with GMP. GMP bioactivity is addressed with special attention on mechanisms of action, signaling pathways involved, and structural characteristics implicated. In addition, the results of various studies dealing with the effects of GMP on models of inflammatory diseases are reviewed and discussed.

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

1976 ◽  
Vol 35 (01) ◽  
pp. 049-056 ◽  
Author(s):  
Christian R Klimt ◽  
P. H Doub ◽  
Nancy H Doub
Keyword(s):  
Myocardial Infarction ◽  
Secondary Prevention ◽  
Case Control ◽  
Therapeutic Effects ◽  
Case Control Studies ◽  
Definitive Answer ◽  
Inhibition Of Platelet Aggregation ◽  
Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

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