scholarly journals In Vitro and In Vivo Characterization of a Bordetella bronchiseptica Mutant Strain with a Deep Rough Lipopolysaccharide Structure

2002 ◽  
Vol 70 (4) ◽  
pp. 1791-1798 ◽  
Author(s):  
Federico Sisti ◽  
Julieta Fernández ◽  
María Eugenia Rodríguez ◽  
Antonio Lagares ◽  
Nicole Guiso ◽  
...  
Keyword(s):  
Parental Strain ◽  
Infection Process ◽  
Bordetella Bronchiseptica ◽  
Host Cells ◽  
Virulence Determinants ◽  
Chronic Infections ◽  
In Vivo Experiments ◽  
Dominant Phenotype

ABSTRACT Bordetella bronchiseptica is closely related to Bordetella pertussis, which produces respiratory disease primarily in mammals other than humans. However, its importance as a human pathogen is being increasingly recognized. Although a large amount of research on Bordetella has been generated regarding protein virulence factors, the participation of the surface lipopolysaccharide (LPS) during B. bronchiseptica infection is less understood. To get a better insight into this matter, we constructed and characterized the behavior of an LPS mutant with the deepest possible rough phenotype. We generated the defective mutant B. bronchiseptica LP39 on the waaC gene, which codes for a heptosyl transferase involved in the biosynthesis of the core region of the LPS molecule. Although in B. bronchiseptica LP39 the production of the principal virulence determinants adenylate cyclase-hemolysin, filamentous hemagglutinin, and pertactin persisted, the quantity of the two latter factors was diminished, with the levels of pertactin being the most greatly affected. Furthermore, the LPS of B. bronchiseptica LP39 did not react with sera obtained from mice that had been infected with the parental strain, indicating that this defective LPS is immunologically different from the wild-type LPS. In vivo experiments demonstrated that the ability to colonize the respiratory tract is reduced in the mutant, being effectively cleared from lungs within 5 days, whereas the parental strain survived at least for 30 days. In vitro experiments have demonstrated that, although B. bronchiseptica LP39 was impaired for adhesion to human epithelial cells, it is still able to survive within the host cells as efficiently as the parental strain. These results seem to indicate that the deep rough form of B. bronchiseptica LPS cannot represent a dominant phenotype at the first stage of colonization. Since isolates with deep rough LPS phenotype have already been obtained from human B. bronchiseptica chronic infections, the possibility that this phenotype arises as a consequence of selection pressure within the host at a late stage of the infection process is discussed.

Antigens ofAspergillus fumigatusexpressed during infection

1995 ◽  
Vol 73 (S1) ◽  
pp. 1087-1091 ◽  
Author(s):  
Jean-Paul Debeaupuis ◽  
Jacqueline Sarfati ◽  
Hidemitsu Kobayashi ◽  
Drion G. Boucias ◽  
Anne Beauvais ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Virulence Gene ◽  
Culture Conditions ◽  
Infection Process ◽  
Host Cells ◽  
Virulence Determinants

Aspergillus fumigatus secretes an array of antigenic molecules in vitro and in vivo. Recent progresses have been made in the characterization and standardization of A. fumigatus antigens useful for the serodiagnosis of aspergillosis. The chymotrypsin antigen has been purified and can be utilized for the diagnosis of aspergillosis occurring in patients with an immunocompetent B cell population. In the case of immunosuppressed patients suffering from invasive aspergillosis, new methods have been developed to detect the galactofuran containing antigen in the serum. The chemical configuration of this molecule is now known. In contrast to their potential in diagnosis, very little progress has been made on the study of the biochemical and pathoimmunological role of these antigens during the infection process. Two reasons can be advanced for this lack of understanding of the virulence determinants. First of all, antigens studied have been produced in vitro in a dextrose rich medium where pH reaches a value below 5 at maximal growth. These culture conditions are very different from the nutritional environment of the lung, which is a protein-based medium with a slightly basic pH. Antigens expressed under these nutritional conditions are very different from the ones detected in vitro. Second, A. fumigatus is an opportunistic fungus which is characterized by a multifactorial virulence. Gene disruption strategy is not adequate to discriminate the role of a factor in the virulence of the fungus. In contrast, as shown by the studies on two toxins of A. fumigatus, a direct effect of an antigen can be seen directly when several fungal molecules are tested in conjunction on host cells. Key words: Aspergillus fumigatus, antigen, invasive aspergillosis, galactomannan, protease.

Effect of bovine lactoferrin onChlamydia trachomatisinfection and inflammation

2017 ◽  
Vol 95 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Rosa Sessa ◽  
Marisa Di Pietro ◽  
Simone Filardo ◽  
Alessia Bressan ◽  
Luigi Rosa ◽  
...  
Keyword(s):  
Acute Infection ◽  
Host Cells ◽  
Developmental Cycle ◽  
Bovine Lactoferrin ◽  
Bacterial Disease ◽  
Chronic Infections ◽  
Sexually Transmitted ◽  
Obligate Intracellular Pathogen

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

scholarly journals Bordetella avium Virulence Measured In Vivo and In Vitro

1998 ◽  
Vol 66 (11) ◽  
pp. 5244-5251 ◽  
Author(s):  
Louise M. Temple ◽  
Alison A. Weiss ◽  
Kimberly E. Walker ◽  
H. John Barnes ◽  
Vern L. Christensen ◽  
...  
Keyword(s):  
Group Size ◽  
Parental Strain ◽  
Upper Respiratory Tract ◽  
Infectious Dose ◽  
Dermonecrotic Toxin ◽  
In Vivo Experiments ◽  
Bordetella Avium ◽  
Mutant Strains

ABSTRACT Bordetella avium causes an upper-respiratory-tract disease called bordetellosis in birds. Bordetellosis shares many of the clinical and histopathological features of disease caused in mammals byBordetella pertussis and Bordetella bronchiseptica. In this study we determined several parameters of infection in the domestic turkey, Meleagris galapavo, and compared these in vivo findings with an in vitro measure of adherence using turkey tracheal rings. In the in vivo experiments, we determined the effects of age, group size, infection duration, and interindividual spread of B. avium. Also, the effect of host genetic background on susceptibility was tested in the five major commercial turkey lines by infecting each with the parental B. avium strain and three B. avium insertion mutants. The mutant strains lacked either motility, the ability to agglutinate guinea pig erythrocytes, or the ability to produce dermonecrotic toxin. The susceptibilities of 1-day-old and 1-week-old turkeys to B. avium were the same, and challenge group size (5, 8, or 10 birds) had no effect upon the 50% infectious dose. Two weeks between inoculation and tracheal culture was optimal, since an avirulent mutant (unable to produce dermonecrotic toxin) persisted for a shorter time. Communicability of the B. aviumparental strain between confined birds was modest, but a nonmotile mutant was less able to spread between birds. There were no host-associated differences in susceptibility to the parental strain and the three B. avium mutant strains just mentioned: in all turkey lines tested, the dermonecrotic toxin- and hemagglutination-negative mutants were avirulent whereas the nonmotile mutants showed no loss of virulence. Interestingly, the ability of a strain to cause disease in vivo correlated completely with its ability to adhere to ciliated tracheal cells in vitro.

Potential Candidates against COVID-19 Targeting RNA-Dependent RNA Polymerase: A Comprehensive Review

2021 ◽  
Vol 22 ◽  
Author(s):  
Neetu Agrawal ◽  
Ahsas Goyal
Keyword(s):  
Rna Polymerase ◽  
In Silico ◽  
Host Cells ◽  
Rna Dependent Rna Polymerase ◽  
In Vivo Experiments ◽  
Contagious Nature ◽  
In Silico Studies ◽  
Viral Enzyme

: Due to the extremely contagious nature of SARS-COV-2, it presents a significant threat to humans worldwide. A plethora of studies are going on all over the world to discover the drug to fight SARS-COV-2. One of the most promising targets is RNA-dependent RNA polymerase (RdRp), responsible for viral RNA replication in host cells. Since RdRp is a viral enzyme with no host cell homologs, it allows the development of selective SARS-COV-2 RdRp inhibitors. A variety of studies used in silico approaches for virtual screening, molecular docking, and repurposing of already existing drugs and phytochemicals against SARS-COV-2 RdRp. This review focuses on collating compounds possessing the potential to inhibit SARS-COV-2 RdRp based on in silico studies to give medicinal chemists food for thought so that the existing drugs can be repurposed for the control and treatment of ongoing COVID-19 pandemic after performing in vitro and in vivo experiments.

scholarly journals Plasmodium Falciparum Infection: In Silico Preliminary Studies

Abakós ◽  
2016 ◽  
Vol 5 (1) ◽  
pp. 63
Author(s):  
Andréia Patricia Gomes ◽  
Brenda Silveira Valles Moreira ◽  
Felipe José Dutra Dias ◽  
Victor Hiroshi Bastos Inoue ◽  
Gabriel Vita Silva Franco ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Ethical Issues ◽  
Plasmodium Knowlesi ◽  
Low Cost ◽  
Plasmodium Malariae ◽  
Infection Process ◽  
Host Cells

<div class="page" title="Page 3"><div class="layoutArea"><div class="column"><p><span>Malaria is an infectious disease of great impact in terms of public health, given the number of people affected and subjected to the risk of illness. Protozoa of the genus Plasmodium cause it and five species can infect humans: </span><em>Plasmodium falciparum</em><span>, </span><em>Plasmodium vivax</em><span>, </span><em>Plasmodium ovale</em><span>, </span><em>Plasmodium malariae </em><span>and </span><em>Plasmodium knowlesi</em><span>; the first is able to produce the most severe cases of the disease. Despite its clinical and epidemiological relevance and investigations in development – targeted at different aspects of the interaction between humans and </span><em>Plasmodium </em><span>protozoa of the genus – there remains many questions about different aspects of the malaria pathophysiology. To study such gaps, interdisciplinary strategies can be pursed, which involve biology, medicine an computer science, as part of the trial </span><span>in silico</span><span>. Such approach provides agility, low cost and does not imply ethical issues that permeate the experiments </span><em>in vitro </em><span>and </span><em>in vivo</em><span>. Based on these considerations, this article presents preliminary results of a computational model of the interaction between </span><em>P. falciparum </em><span>and erythrocytes, implemented in </span><em>AutoSimmune </em><span>system. The results obtained show that the system is able to simulate the host cells infection process by protozoan with similarities with the biological reality. </span></p></div></div></div>

scholarly journals Pseudomonas aeruginosa RsmA Plays an Important Role during Murine Infection by Influencing Colonization, Virulence, Persistence, and Pulmonary Inflammation

2007 ◽  
Vol 76 (2) ◽  
pp. 632-638 ◽  
Author(s):  
Heidi Mulcahy ◽  
Julie O'Callaghan ◽  
Eoin P. O'Grady ◽  
María D. Maciá ◽  
Nuria Borrell ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Environmental Conditions ◽  
Pulmonary Inflammation ◽  
Acute Infection ◽  
Regulatory Protein ◽  
Airway Epithelial Cells ◽  
Virulence Determinants ◽  
Chronic Infections

ABSTRACT The ability of Pseudomonas aeruginosa to cause a broad range of infections in humans is due, at least in part, to its adaptability and its capacity to regulate the expression of key virulence genes in response to specific environmental conditions. Multiple two-component response regulators have been shown to facilitate rapid responses to these environmental conditions, including the coordinated expression of specific virulence determinants. RsmA is a posttranscriptional regulatory protein which controls the expression of a number of virulence-related genes with relevance for acute and chronic infections. Many membrane-bound sensors, including RetS, LadS, and GacS, are responsible for the reciprocal regulation of genes associated with acute infection and chronic persistence. In P. aeruginosa this is due to sensors influencing the expression of the regulatory RNA RsmZ, with subsequent effects on the level of free RsmA. While interactions between an rsmA mutant and human airway epithelial cells have been examined in vitro, the role of RsmA during infection in vivo has not been determined yet. Here the function of RsmA in both acute and chronic models of infection was examined. The results demonstrate that RsmA is involved in initial colonization and dissemination in a mouse model of acute pneumonia. Furthermore, while loss of RsmA results in reduced colonization during the initial stages of acute infection, the data show that mutation of rsmA ultimately favors chronic persistence and results in increased inflammation in the lungs of infected mice.

scholarly journals In Vitro Activities of Azithromycin and Ofloxacin againstChlamydia pneumoniae in a Continuous-Infection Model

1999 ◽  
Vol 43 (9) ◽  
pp. 2268-2272 ◽  
Author(s):  
Andrei Kutlin ◽  
Patricia M. Roblin ◽  
Margaret R. Hammerschlag
Keyword(s):  
Chlamydia Pneumoniae ◽  
In Vitro Study ◽  
Community Acquired Pneumonia ◽  
Host Cells ◽  
Infection Model ◽  
Chronic Infections ◽  
Adults And Children ◽  
Infected Cells

ABSTRACT Chlamydia pneumoniae is a well-established cause of community-acquired pneumonia and bronchitis in adults and children. Chronic infections with C. pneumoniae have been implicated in the development of atherosclerosis and other diseases in humans. Methods currently used for the culture and propagation ofC. pneumoniae are not analogous to the infection as it occurs in vivo. We have established a model of continuous C. pneumoniae infection in vitro. HEp-2 cells inoculated with CM-1 and TW-183 strains have been persistently infected for periods of over 1.5 and 2 years, respectively. The cultures were maintained without centrifugation or the addition of cycloheximide, fresh host cells, or chlamydia. We observed cycles of host cell lysis, detachment, and regrowth with both strains of C. pneumoniae. Continuous C. pneumoniae infections may more closely resemble the actual events as they occur in vivo and, therefore, may be a better model for the in vitro study of C. pneumoniae infection. When we used continuously infected cells to determine the effects of azithromycin and ofloxacin on C. pneumoniae propagation in vitro, we found that both drugs reduced but did not completely eliminate the organism. This may be an important observation, as the failure of antibiotic therapy against C. pneumoniae infection in humans has been described.

scholarly journals Virulence of Leishmania infantum Is Expressed as a Clonal and Dominant Phenotype in Experimental Infections

2001 ◽  
Vol 69 (12) ◽  
pp. 7365-7373 ◽  
Author(s):  
Yves Jean-François Garin ◽  
Annie Sulahian ◽  
Francine Pratlong ◽  
Pascale Meneceur ◽  
Jean-Pierre Gangneux ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Virulent Strain ◽  
Biological Marker ◽  
In Vivo Experiments ◽  
Dominant Phenotype ◽  
Virulence Phenotype ◽  
Parasite Populations

ABSTRACT Human Leishmania infantum infection results in a spectrum of clinical expressions ranging from cutaneous to either asymptomatic or fatal visceral disease. In this context, characterization of parasite virulence appears to be relevant as a biological marker of intrinsic parasitic factors that can affect the pathology of leishmaniasis. Since parasite populations in naturally infected hosts are likely to be composed of multiclonal associations, we first explored the biodiversity of parasite virulence at the intrastrain level in vitro and in vivo by using 11 clones isolated from three strains previously known to express different virulence phenotypes in mice. Subsequently, we studied the course of infection in mice inoculated simultaneously or successively with strains or clones showing various virulence phenotypes. Analysis of in vitro growth characteristics showed no differences among clones from the different parental strains. By contrast, in vivo experiments evidenced a marked intrastrain heterogeneity of virulence to mice. One out of five clones obtained from a virulent strain showed a typical virulence phenotype, while the remaining four clones had low-virulence profiles, as did the six clones isolated from two low-virulence strains. In mixed multiclonal infections, the virulence phenotype was expressed as a dominant character over the associated low-virulence clones. After a challenge with either a homologous or a heterologous strain or clone, virulence phenotypes were conserved and expressed as in naive mice independently from the preexisting population. These results strongly suggest that parasite virulence in L. infantum visceral leishmaniasis is clonal and dominant in nature.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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