scholarly journals Increased Chain Length Promotes Pneumococcal Adherence and Colonization

2012 ◽  
Vol 80 (10) ◽  
pp. 3454-3459 ◽  
Author(s):  
Jesse L. Rodriguez ◽  
Ankur B. Dalia ◽  
Jeffrey N. Weiser
Keyword(s):  
Parental Strain ◽  
A549 Cells ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Epithelial Surface ◽  
Content Type ◽  
Morphological Heterogeneity ◽  
Upper Respiratory

ABSTRACTStreptococcus pneumoniaeis a mucosal pathogen that grows in chains of variable lengths. Short-chain forms are less likely to activate complement, and as a consequence they evade opsonophagocytic clearance more effectively during invasive disease. When grown in human nasal airway surface fluid, pneumococci exhibited both short- and long-chain forms. Here, we determined whether longer chains provide an advantage during colonization when the organism is attached to the epithelial surface. Chain-forming mutants and the parental strain grown under conditions to promote chain formation showed increased adherence to human epithelial cells (A549 cells)in vitro. Additionally, adherence to A549 cells selected for longer chains within the wild-type strain.In vivoin a murine model of colonization, chain-forming mutants outcompeted the parental strain. Together, our results demonstrate that morphological heterogeneity in the pneumococcus may promote colonization of the upper respiratory tract by enhancing the ability of the organism to bind to the epithelial surface.

scholarly journals Demonstration of N , N -Dimethyldithiocarbamate as a Copper-Dependent Antibiotic against Multiple Upper Respiratory Tract Pathogens

2021 ◽  
Author(s):  
Sanjay V. Menghani ◽  
Angela Rivera ◽  
Miranda Neubert ◽  
James R. Hagerty ◽  
Lourdes Lewis ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Dependent Manner ◽  
Upper Respiratory Tract ◽  
Coccidioides Posadasii ◽  
Content Type ◽  
Upper Respiratory

With the rise of antibiotic resistance, approaches that add new antimicrobials to the current repertoire are vital. Here, we investigate putative and known copper ionophores in an attempt to intoxicate bacteria and use ionophore/copper synergy, and we ultimately find success with N , N -dimethyldithiocarbamate (DMDC). We show that DMDC has in vitro efficacy in a copper-dependent manner and kills pathogens across three different kingdoms, Streptococcus pneumoniae ( Sr. pneumoniae ), Coccidioides posadasii , and Schistosoma mansoni , and in vivo efficacy against Sr . pneumoniae .

scholarly journals Role of LecA and LecB Lectins in Pseudomonas aeruginosa-Induced Lung Injury and Effect of Carbohydrate Ligands

2009 ◽  
Vol 77 (5) ◽  
pp. 2065-2075 ◽  
Author(s):  
Chanez Chemani ◽  
Anne Imberty ◽  
Sophie de Bentzmann ◽  
Maud Pierre ◽  
Michaela Wimmerová ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Parental Strain ◽  
A549 Cells ◽  
Carbohydrate Ligands ◽  
Vitro Model

ABSTRACT Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA- and Lec B-specific lectin-inhibiting carbohydrates (α-methyl-galactoside and α-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on A549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.

scholarly journals Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G Alters Transcription of Key Inflammatory Mediators In Vitro and In Vivo

2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Mauricio J. C. Coppo ◽  
Joanne M. Devlin ◽  
Alistair R. Legione ◽  
Paola K. Vaz ◽  
Sang-Won Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Protein ◽  
Upper Respiratory Tract ◽  
Infectious Laryngotracheitis Virus ◽  
Glycoprotein G ◽  
Infectious Laryngotracheitis ◽  
Upper Respiratory ◽  
Laryngotracheitis Virus

ABSTRACTInfectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects chickens, causing upper respiratory tract disease and significant losses to poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral chemokine-binding protein conserved among most alphaherpesviruses, including ILTV. A number of studies comparing the immunological parameters between infection with gG-expressing and gG-deficient ILTV strains have demonstrated that expression of gG is associated with increased virulence, modification of the amount and the composition of the inflammatory response, and modulation of the immune responses toward antibody production and away from cell-mediated immune responses. The aims of the current study were to examine the establishment of infection and inflammation by ILTV and determine how gG influences that response to infection.In vitroinfection studies using tracheal organ tissue specimen cultures and blood-derived monocytes andin vivoinfection studies in specific-pathogen-free chickens showed that leukocyte recruitment to the site of infection is an important component of the induced pathology and that this is influenced by the expression of ILTV gG and changes in the transcription of the chicken orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and chicken CXCLi2, among other cytokines and chemokines. The results from this study demonstrate that ILTV gG interferes with chemokine and cytokine transcription at different steps of the inflammatory cascade, thus altering inflammation, virulence, and the balance of the immune response to infection.IMPORTANCEInfectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a conserved broad-range viral chemokine-binding protein known to interfere with host immune responses. However, little is known about how gG modifies virulence and influences the inflammatory signaling cascade associated with infection. Here, data fromin vitroandin vivoinfection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligandsin vitro(such as chicken CXCL8 orthologues, among others), which explains the altered balance of the inflammatory response that is associated with gG during ILTV infection of the upper respiratory tract of chickens. This is the first report to associate gG with the dysregulation of cytokine transcription at different stages of the inflammatory cascade triggered by ILTV infection of the natural host.

scholarly journals Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection

2014 ◽  
Vol 82 (11) ◽  
pp. 4607-4619 ◽  
Author(s):  
Melinda M. Pettigrew ◽  
Laura R. Marks ◽  
Yong Kong ◽  
Janneane F. Gent ◽  
Hazeline Roche-Hakansson ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lactate Production ◽  
Invasive Disease ◽  
Content Type ◽  
Induced Changes ◽  
Upregulated Genes

ABSTRACTStreptococcus pneumoniaeis a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilmsin vitroandin vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare theS. pneumoniaetranscriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersedS. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies ofS. pneumoniaepathogenesis.

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.

scholarly journals Dolosigranulum pigrum Cooperation and Competition in Human Nasal Microbiota

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Silvio D. Brugger ◽  
Sara M. Eslami ◽  
Melinda M. Pettigrew ◽  
Isabel F. Escapa ◽  
Matthew T. Henke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Genomic Analysis ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Microbe Interactions ◽  
Clinical Experiments ◽  
Nasal Microbiota

ABSTRACT Multiple epidemiological studies identify Dolosigranulum pigrum as a candidate beneficial bacterium based on its positive association with health, including negative associations with nasal/nasopharyngeal colonization by the pathogenic species Staphylococcus aureus and Streptococcus pneumoniae. Using a multipronged approach to gain new insights into D. pigrum function, we observed phenotypic interactions and predictions of genomic capacity that support the idea of a role for microbe-microbe interactions involving D. pigrum in shaping the composition of human nasal microbiota. We identified in vivo community-level and in vitro phenotypic cooperation by specific nasal Corynebacterium species. Also, D. pigrum inhibited S. aureus growth in vitro, whereas robust inhibition of S. pneumoniae required both D. pigrum and a nasal Corynebacterium together. D. pigrum l-lactic acid production was insufficient to account for these inhibitions. Genomic analysis of 11 strains revealed that D. pigrum has a small genome (average 1.86 Mb) and multiple predicted auxotrophies consistent with D. pigrum relying on its human host and on cocolonizing bacteria for key nutrients. Further, the accessory genome of D. pigrum harbored a diverse repertoire of biosynthetic gene clusters, some of which may have a role in microbe-microbe interactions. These new insights into D. pigrum’s functions advance the field from compositional analysis to genomic and phenotypic experimentation on a potentially beneficial bacterial resident of the human upper respiratory tract and lay the foundation for future animal and clinical experiments. IMPORTANCE Staphylococcus aureus and Streptococcus pneumoniae infections cause significant morbidity and mortality in humans. For both, nasal colonization is a risk factor for infection. Studies of nasal microbiota identify Dolosigranulum pigrum as a benign bacterium present when adults are free of S. aureus or when children are free of S. pneumoniae. Here, we validated these in vivo associations with functional assays. We found that D. pigrum inhibited S. aureus in vitro and, together with a specific nasal Corynebacterium species, also inhibited S. pneumoniae. Furthermore, genomic analysis of D. pigrum indicated that it must obtain key nutrients from other nasal bacteria or from humans. These phenotypic interactions support the idea of a role for microbe-microbe interactions in shaping the composition of human nasal microbiota and implicate D. pigrum as a mutualist of humans. These findings support the feasibility of future development of microbe-targeted interventions to reshape nasal microbiota composition to exclude S. aureus and/or S. pneumoniae.

Antiviral Properties of Food Plants Could Help to Reduce Contagion and Severity in SARS-CoV-2 Infections

2021 ◽  
Vol 07 ◽  
Author(s):  
Betina Cardoso
Keyword(s):  
Respiratory Tract ◽  
Literature Search ◽  
Food Plants ◽  
Upper Respiratory Tract ◽  
Site Specific ◽  
In Vivo Experiments ◽  
Upper Respiratory ◽  
Novel Coronavirus

Introduction: The importance of an immediate tool to help patients and prevent viral diffusion of new pneumonia caused by 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) that causes the disease COVID-19 becomes evident. Recent articles have reported on body site-specific SARS-CoV-2 infection, showing very active replication in the throat and upper respiratory tract when symptoms were still mild, and thus being efficient in viral transmission in sputum. Material and Methods: An alternative that may be feasible is to resort to scientific studies that demonstrate the antiviral potential of medicinal plants species through in-vitro and in-vivo experiments to alleviate symptoms and prevent the spread of contagion. A literature search in Scopus and PubMed on herbs and foods with antiviral properties was performed. Results: Herbs and foods with demonstrated antiviral potential have been identified, which could limit SARS-CoV-2 spreading by interfering on ACE2 protein on infection sites. The analysis of transdisciplinary knowledge allows us to connect previous research on the action of common plants and foods on viruses to limit the replication of SARS-CoV-2 in the throat and upper respiratory tract. Conclusions: Herbs and foods with demonstrated antiviral potential have been identified, which could limit SARS-CoV-2 spreading by interfering on ACE2 protein on infection sites. The analysis of transdisciplinary knowledge allows us to connect previous research on the action of common plants and foods on viruses to limit the replication of SARS-CoV-2 in the throat and upper respiratory tract.

A Review of Topical Povidone-iodine to Decrease Viral Load of COViD-19

2021 ◽  
Vol 36 (5) ◽  
pp. 238-241
Author(s):  
Katherine M. Benson ◽  
Amalia A. Mancini ◽  
Michael R. Brodeur
Keyword(s):  
Viral Load ◽  
Respiratory Tract Infections ◽  
Povidone Iodine ◽  
Preventive Measure ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Clinical Trial Results ◽  
Tract Infections

Topical povidone-iodine (PVP-I) is currently being considered as a potential preventive measure against the spread of COVID-19. Diluted PVP-I solutions have been historically used in Asia to treat upper respiratory tract infections (URTIs) by decreasing the bacterial and viral load on oropharyngeal mucosa to decrease the transmission of diseases. Efficacy of gargling 0.23% PVP-I mouthwash in Japan demonstrated to be efficacious in lowering the prevalence of URTIs when compared with placebo. The 0.23% concentration was used in vitro on severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, which produced undetectable results after 30 seconds of exposure. Additionally, a recent study in 2020 proved the efficacy of PVP-I 0.45%-10% in reducing COVID-19 (SARS-CoV 2) viral load in vitro. Numerous clinical trials are being conducted to determine if there is a decrease in viral load, and thus transmission, when using oral or nasal topical PVP-I in COVID-19 patients. Because of the current lack of evidence for the use of PVP-I in vivo with COVID-19, it is recommended to await the clinical trial results before initiating this practice.

scholarly journals Recombinant Respiratory Syncytial Virus That Does Not Express the NS1 or M2-2 Protein Is Highly Attenuated and Immunogenic in Chimpanzees

2000 ◽  
Vol 74 (19) ◽  
pp. 9317-9321 ◽  
Author(s):  
Michael N. Teng ◽  
Stephen S. Whitehead ◽  
Alison Bermingham ◽  
Marisa St. Claire ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Neutralizing Antibody ◽  
Target Population ◽  
Large Deletion ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Upper Respiratory ◽  
Syncytial Virus

ABSTRACT Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2ΔNS1 and rA2ΔM2-2, respectively, were evaluated as live-attenuated RSV vaccines. The rA2ΔNS1 virus contains a large deletion that should have the advantageous property of genetic stability during replication in vitro and in vivo. In vitro, rA2ΔNS1 replicated approximately 10-fold less well than wild-type recombinant RSV (rA2), while rA2ΔM2-2 had delayed growth kinetics but reached a final titer similar to that of rA2. Each virus was administered to the respiratory tracts of RSV-seronegative chimpanzees to assess replication, immunogenicity, and protective efficacy. The rA2ΔNS1 and rA2ΔM2-2 viruses were 2,200- to 55,000-fold restricted in replication in the upper and lower respiratory tracts but induced a level of RSV-neutralizing antibody in serum that was only slightly reduced compared to the level induced by wild-type RSV. The replication of wild-type RSV in immunized chimpanzees after challenge was reduced more than 10,000-fold at each site. Importantly, rA2ΔNS1 and rA2ΔM2-2 were 10-fold more restricted in replication in the upper respiratory tract than was thecpts248/404 virus, a vaccine candidate that retained mild reactogenicity in the upper respiratory tracts of 1-month-old infants. Thus, either rA2ΔNS1 or rA2ΔM2-2 might be appropriately attenuated for this age group, which is the major target population for an RSV vaccine. In addition, these results show that neither NS1 nor M2-2 is essential for RSV replication in vivo, although each is important for efficient replication.

A rat nasal epithelial model for predicting upper respiratory tract toxicity: in vivo–in vitro correlations

Toxicology ◽  
2000 ◽  
Vol 145 (1) ◽  
pp. 39-49 ◽  
Author(s):  
J.D Kilgour ◽  
S.A Simpson ◽  
D.J Alexander ◽  
C.J Reed
Keyword(s):  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
Upper Respiratory
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