scholarly journals Resident bacteria contribute to opportunistic infections of the respiratory tract

2021 ◽  
Vol 17 (3) ◽  
pp. e1009436
Author(s):  
Yifan Wu ◽  
Yongqiang Wang ◽  
Huiming Yang ◽  
Qian Li ◽  
Xiaoxia Gong ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Opportunistic Infections ◽  
Dominant Role ◽  
Growth Dynamics ◽  
Host Cells ◽  
Opportunistic Pathogens ◽  
New Paradigm ◽  
Model Animal ◽  
Avibacterium Paragallinarum

Opportunistic pathogens frequently cause volatile infections in hosts with compromised immune systems or a disrupted normal microbiota. The commensalism of diverse microorganisms contributes to colonization resistance, which prevents the expansion of opportunistic pathogens. Following microbiota disruption, pathogens promptly adapt to altered niches and obtain growth advantages. Nevertheless, whether and how resident bacteria modulate the growth dynamics of invasive pathogens and the eventual outcome of such infections are still unclear. Here, we utilized birds as a model animal and observed a resident bacterium exacerbating the invasion of Avibacterium paragallinarum (previously Haemophilus paragallinarum) in the respiratory tract. We first found that negligibly abundant Staphylococcus chromogenes, rather than Staphylococcus aureus, played a dominant role in Av. paragallinarum-associated infectious coryza in poultry based on epidemic investigations and in vitro analyses. Furthermore, we determined that S. chromogenes not only directly provides the necessary nutrition factor nicotinamide adenine dinucleotide (NAD+) but also accelerates its biosynthesis and release from host cells to promote the survival and growth of Av. paragallinarum. Last, we successfully intervened in Av. paragallinarum-associated infections in animal models using antibiotics that specifically target S. chromogenes. Our findings show that opportunistic pathogens can hijack commensal bacteria to initiate infection and expansion and suggest a new paradigm to ameliorate opportunistic infections by modulating the dynamics of resident bacteria.

scholarly journals Role of Adhesin Release for Mucosal Colonization by a Bacterial Pathogen

2003 ◽  
Vol 197 (6) ◽  
pp. 735-742 ◽  
Author(s):  
Loïc Coutte ◽  
Sylvie Alonso ◽  
Nathalie Reveneau ◽  
Eve Willery ◽  
Brigitte Quatannens ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Bacterial Pathogen ◽  
Host Cells ◽  
Wild Type ◽  
Early Step ◽  
Bacterial Surface ◽  
Extracellular Milieu ◽  
Wild Type Parent

Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract.

scholarly journals Strategy To Create Chimeric Proteins Derived from Functional Adhesin Regions of Mycoplasma pneumoniae for Vaccine Development

2009 ◽  
Vol 77 (11) ◽  
pp. 5007-5015 ◽  
Author(s):  
Nicol Schurwanz ◽  
Enno Jacobs ◽  
Roger Dumke
Keyword(s):  
Respiratory Tract ◽  
Mycoplasma Pneumoniae ◽  
Recombinant Proteins ◽  
Vaccine Development ◽  
Chimeric Protein ◽  
Host Cells ◽  
Vitro Assay ◽  
Bronchial Epithelial ◽  
First Time

ABSTRACT The cell wall-less bacterium Mycoplasma pneumoniae is one of the most common agents of respiratory tract diseases in humans. Adhesin-mediated binding of the bacteria to host cells is a crucial step in colonization and subsequent pathogenesis. For the first time, we expressed 16 recombinant proteins covering almost the whole major adhesin P1 and the adherence-associated protein P30 to characterize these proteins immunologically and functionally. We describe a new in vitro assay using several human cell lines in combination with fluorescence-activated cell sorting analysis to screen antisera raised against the recombinant proteins quantitatively for adherence inhibition activity. The protein derived from the nearly C-terminal part of the P1 adhesin (amino acids [aa] 1288 to 1518) and the protein P30 (aa 17 to 274) especially showed prominent immunoreactivity with sera from M. pneumoniae-immunized guinea pigs as well as with M. pneumoniae-positive patient sera. We demonstrate that the same protein regions are involved in mediating cytadherence since antibodies against these adhesin regions decrease mycoplasma adhesion to human cells significantly. For further vaccine studies, we optimized the immunogenic and adherence-mediating properties of the antigen by combining both the P1 and the P30 regions in a novel chimeric protein. Antibodies against this protein show an increased reduction of M. pneumoniae adherence to human bronchial epithelial cells by 95%, which is comparable to results with polyspecific anti-M. pneumoniae animal serum. Our strategy results in a promising defined antigen candidate for reducing or even preventing M. pneumoniae colonization of the respiratory tract in future vaccination studies.

scholarly journals In Vitro Activities of a Novel Nanoemulsion against Burkholderia and Other Multidrug-Resistant Cystic Fibrosis-Associated Bacterial Species

2008 ◽  
Vol 53 (1) ◽  
pp. 249-255 ◽  
Author(s):  
John J. LiPuma ◽  
Sivaprakash Rathinavelu ◽  
Bridget K. Foster ◽  
Jordan C. Keoleian ◽  
Paul E. Makidon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Burkholderia Cepacia ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Opportunistic Pathogens ◽  
Oil In Water ◽  
Distinct Strain ◽  
Treatment Of Infection

ABSTRACT Respiratory tract infection, most often involving opportunistic bacterial species with broad-spectrum antibiotic resistance, is the primary cause of death in persons with cystic fibrosis (CF). Species within the Burkholderia cepacia complex are especially problematic in this patient population. We investigated a novel surfactant-stabilized oil-in-water nanoemulsion (NB-401) for activity against 150 bacterial isolates recovered primarily from CF respiratory tract specimens. These specimens included 75 Burkholderia isolates and 75 isolates belonging to other CF-relevant species including Pseudomonas, Achromobacter, Pandoraea, Ralstonia, Stenotrophomonas, and Acinetobacter. Nearly one-third of the isolates were multidrug resistant, and 20 (13%) were panresistant based on standard antibiotic testing. All isolates belonging to the same species were genotyped to ensure that each isolate was a distinct strain. The MIC90 of NB-401 was 125 μg/ml. We found no decrease in activity against multidrug-resistant or panresistant strains. MBC testing showed no evidence of tolerance to NB-401. We investigated the activity of NB-401 against a subset of strains grown as a biofilm and against planktonic strains in the presence of CF sputum. Although the activity of NB-401 was decreased under both conditions, the nanoemulsion remained bactericidal for all strains tested. These results support NB-401's potential role as a novel antimicrobial agent for the treatment of infection due to CF-related opportunistic pathogens.

scholarly journals Carbohydrate Moieties of Microsporidian Polar Tube Proteins Are Targeted by Immunoglobulin G in Immunocompetent Individuals

2005 ◽  
Vol 73 (12) ◽  
pp. 7906-7913 ◽  
Author(s):  
Ron Peek ◽  
Frédéric Delbac ◽  
Dave Speijer ◽  
Valérie Polonais ◽  
Sophie Greve ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Gel Electrophoresis ◽  
Blood Donors ◽  
Host Cells ◽  
Opportunistic Pathogens ◽  
Polar Tube ◽  
Two Dimensional Gel Electrophoresis ◽  
Encephalitozoon Intestinalis ◽  
Chemical Deglycosylation

ABSTRACT Microsporidia of the Encephalitozoon species are frequently found as opportunistic pathogens of immunocompromised patients, but very little is known about the prevalence and significance of Encephalitozoon infection in immunocompetent individuals. It was reported previously that 8% of Dutch blood donors and 5% of pregnant French women had an immunoglobulin G (IgG) immune response against specific organelles of Encephalitozoon intestinalis. These organelles, the so-called polar tube and anchoring disk, are used to penetrate membranes of host cells during infection. The unexpectedly high percentage of immunocompetent individuals with IgG against these organelles suggested that infection of humans with microsporidia might be more common than previously recognized. In the present study, we analyzed this anti-Encephalitozoon IgG response by using indirect immunofluorescence, Western blotting, two-dimensional gel electrophoresis, and chemical deglycosylation. Our results show that the antibody response is directed against the posttranslational carbohydrate modification of the major polar tube protein (polar tube protein 1) and carbohydrate moieties of proteins in the anchoring region of the polar tube of Encephalitozoon. In addition, the antibodies were found to decrease the infectivity of E. intestinalis in vitro. The significance and possible origin of these prevalent antibodies are discussed.

Biologic Immunomodulatory Drugs and Infection in the Respiratory Tract of Nonhuman Primates

2020 ◽  
pp. 019262332094670
Author(s):  
Thierry D. Flandre ◽  
Alessandro Piaia ◽  
Maurice G. Cary
Keyword(s):  
Respiratory Tract ◽  
Nonhuman Primates ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Pulmonary Inflammation ◽  
Opportunistic Pathogen ◽  
Clinical Disease ◽  
Immunomodulatory Drugs ◽  
Opportunistic Pathogens ◽  
Protective Response

Though rare due to measures and practices to control the risk, infections can occur in research and toxicology studies, especially in nonhuman primates (NHPs) exposed to xenobiotics, particularly immunomodulatory drugs. With such xenobiotics, immunocompromised or immunosuppressed animals will not be able to mount a protective response to infection by an opportunistic pathogen (bacteria, virus, parasite, or fungus) that might otherwise be nonpathogenic and remain clinically asymptomatic in immunocompetent animals. The respiratory tract is one of the most commonly affected systems in clinic, but also in toxicology studies. Pulmonary inflammation will be the main finding associated with opportunistic infections and may cause overt clinical disease with even early sacrifice or death, and may compromise or complicate the pathology evaluation. It is important to properly differentiate the various features of infection, to be aware of the range of possible opportunistic pathogens and how they may impact the interpretation of pathology findings. This review will present the most common bacterial, viral, parasitic, and fungal infections observed in the respiratory tract in NHPs during research and/or toxicology studies.

Opportunistic Infections Are Uncommon with Dasatinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1120-1120 ◽  
Author(s):  
Ali Al-Ameri ◽  
Hagop Kantarjian ◽  
Gautam Borthakur ◽  
Erkut Bahceci ◽  
Ted Szatrowski ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Opportunistic Infections ◽  
Phase Iii ◽  
Opportunistic Pathogens ◽  
Once Daily ◽  
Grade 3 ◽  
Dasatinib Treatment

Abstract Abstract 1120 Poster Board I-142 BACKGROUND Dasatinib is a tyrosine kinase inhibitor that can achieve rapid and durable hematological, cytogenetic, and molecular responses in patients with CML-CP after resistance or intolerance to imatinib. Three years of follow-up data have been accumulated, with progression-free survival rates of 73% reported for second-line dasatinib 100 mg once daily (the currently approved dose for CML-CP). In addition to BCR-ABL, dasatinib inhibits Src family kinases (SFKs) and thereby mitigates T-cell receptor-mediated signaling. Dasatinib may have unique immunomodulatory properties. Modulation of CD8+ T-cell intracellular signal transduction, cellular proliferation, and cytokine production by dasatinib has been previously reported in vitro (Fei F. Exp Hematol. 2008;36(10):1297-308). Also, dasatinib has been shown to induce expansion of T-cells and NK cells in the clinic, an effect that was associated with achieving a complete molecular response (Mustjoki S. Leukemia. 2009;23(8):1398-405). Opportunistic infections (OI) like herpes zoster infections (HZV) have been previously reported with imatinib, albeit at a low rate (Mattiuzzi GN. Clin Cancer Res. 2003;9(3):976-80). AIM To determine the frequency of OI in clinical trials of dasatinib in CML-CP. METHODS Data from phase II CA180-013 and CA180-017, and phase III CA180-034 trial databases of 1150 CML-CP patients, collectively, were reviewed. A search for infection adverse events was conducted, and entries related to opportunistic pathogens were identified and tabulated. The follow-up time is ≥3 years for all patients in the phase III study and 2 years in the phase II studies. The median time on dasatinib treatment for patients treated with 100 mg once daily is 31 months, and for other doses is 25 months. RESULTS Of the 165 patients treated with dasatinib 100 mg once daily, only one grade 3–4 OI was identified (incidence <1%): a grade 3 HZV infection. In addition, there were 18 cases (11%) of grade 1–2 herpes simplex (HSV), 3 HZV, and one mycobacterial infection. Thirteen of the HSV cases were reported as not related to dasatinib treatment. Among 985 patients treated with other dosing schedules (50 mg twice daily, 70 mg twice daily, or 140 mg once daily), 7 cases (<1%) of grade 3–4 OIs were identified: 1 cytomegalovirus, 2 HSV, 1 HZV, 2 pneumocystis, and 1 unspecified fungal infection. There were 87 (9%) grade 1–2 HSV cases reported in the other dosing arms, but 62 were deemed not associated with dasatinib. There were 23 reports (2%) of grade 1–2 HZV infection with other doses, and one case of a grade 2 cytomegalovirus infection. CONCLUSION Our analysis indicates that OIs are rare in patients with CML-CP treated with dasatinib. Most of the infections associated with opportunistic pathogens were grade 1–2. Thus, despite in vitro data suggesting immunosuppressive properties of dasatinib, there do not seem to be adverse clinical consequences with this agent. Disclosures Kantarjian: Bristol-Myers Squibb: Research Funding; Novartis: Research Funding. Borthakur:Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau; Celgene: Speakers Bureau. Bahceci:Bristol-Myers Squibb: Employment. Szatrowski:Bristol-Myers Squibb: Employment. Damokosh:Bristol-Myers Squibb: Employment. Cortes:Bristol-Myers Squibb: Research Funding.

scholarly journals Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1725
Author(s):  
Justine Oliva ◽  
Olivier Terrier
Keyword(s):  
Respiratory Tract ◽  
Current Knowledge ◽  
Influenza Infection ◽  
Public Health Problem ◽  
Experimental Models ◽  
Influenza Viruses ◽  
Host Cells ◽  
Tract Infections

Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral–bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.

Bioactivity of Phenolic Compounds Extracted from Strawberry against Formation of Pseudomonas aeruginosa Biofilm

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Baydaa Hussein ◽  
Zainab A. Aldhaher ◽  
Shahrazad Najem Abdu-Allah ◽  
Adel Hamdan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phenolic Compounds ◽  
Biofilm Formation ◽  
Opportunistic Infections ◽  
Formation Rate ◽  
Hydrocarbon Chain ◽  
Health Concern ◽  
Gas Chromatography Mass Spectrometry ◽  
Phenolic Contents

Background: Biofilm is a bacterial way of life prevalent in the world of microbes; in addition to that it is a source of alarm in the field of health concern. Pseudomonas aeruginosa is a pathogenic bacterium responsible for all opportunistic infections such as chronic and severe. Aim of this study: This paper aims to provide an overview of the promotion of isolates to produce a biofilm in vitro under special circumstances, to expose certain antibiotics to produce phenotypic evaluation of biofilm bacteria. Methods and Materials: Three diverse ways were used to inhibited biofilm formation of P.aeruginosa by effect of phenolic compounds extracts from strawberries. Isolates produced biofilm on agar MacConkey under certain circumstances. Results: The results showed that all isolates were resistant to antibiotics except sensitive to azithromycin (AZM, 15μg), and in this study was conducted on three ways to detect the biofilm produced, has been detected by the biofilm like Tissue culture plate (TCP), Tube method (TM), Congo Red Agar (CRA). These methods gave a clear result of these isolates under study. Active compounds were analyzed in both extracts by Gas Chromatography-mass Spectrometry which indicate High molecular weight compound with a long hydrocarbon chain. Conclusion: Phenolic compounds could behave as bioactive material and can be useful to be used in pharmaceutical synthesis. Phenolic contents which found in leaves and fruits extracts of strawberries shows antibacterial activity against all strains tested by the ability to reduce the production of biofilm formation rate.

Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration

2020 ◽  
Vol 16 ◽  
Author(s):  
Jogendra Singh Nim ◽  
Mohit Yadav ◽  
Lalit Kumar Gautam ◽  
Chaitali Ghosh ◽  
Shakti Sahi ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Functional Characterization ◽  
Host Cells ◽  
System Control ◽  
Xenorhabdus Nematophila ◽  
Functional Features ◽  
Dynamics Simulations ◽  
Species Specific ◽  
Rna Interaction

Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn-MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, XnMazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.

Sign in / Sign up

Export Citation Format

Share Document