scholarly journals The Role of the Moraxella catarrhalis CopB Protein in Facilitating Iron Acquisition From Human Transferrin and Lactoferrin

2021 ◽  
Vol 12 ◽  
Author(s):  
Clement Chan ◽  
Dixon Ng ◽  
Anthony B. Schryvers
Keyword(s):  
Outer Membrane ◽  
Indirect Effect ◽  
Moraxella Catarrhalis ◽  
Respiratory Infections ◽  
Binding Protein ◽  
Protein A ◽  
Upper Respiratory Tract ◽  
Human Transferrin ◽  
Upper Respiratory ◽  
The Impact

Moraxella catarrhalis is a Gram-negative bacterium that is responsible for a substantial proportion of upper respiratory infections in children and lower respiratory infections in the elderly. Moraxella catarrhalis resides exclusively on the mucosal surfaces of the upper respiratory tract of humans and is capable of directly acquiring iron for growth from the host glycoproteins human transferrin (hTf) and human lactoferrin (hLf). The iron-bound form of these glycoproteins is initially captured by the surface lipoproteins Tf or Lf binding protein B (TbpB or LbpB) and delivered to the integral outer membrane TonB-dependent transport (TBDT) proteins, Tf binding protein A (TbpA) or Lf binding protein A (LbpA). The extraction of iron involves conformational changes in Lf and Tf to facilitate iron removal followed by its transport across the outer membrane by a well characterized process for TBDTs. Surprisingly the disruption of the gene encoding another TBDT, CopB, results in a reduction in the ability to grow on human Tf or Lf. The possibility that this could have been due to an artifact of mutant construction that resulted in the inhibition of TonB-mediated process was eliminated by a complete deletion of the CopB gene. A systematic evaluation of the impact on growth under various conditions by deletions of the genes encoding TbpA, LbpA, and CopB as well as mutations of the iron liganding residues and TonB box region of CopB was implemented. The results indicate that although CopB is capable of effectively acquiring iron from the growth medium, it does not directly acquire iron from Tf or Lf. We propose that the indirect effect on iron transport from Tf and Lf by CopB could possibly be explained by the association of TBDTs at gaps in the peptidoglycan layer that may enhance the efficiency of the process. This concept is supported by previous studies demonstrating an indirect effect on growth of Tf and Lf by deletion of the peptidoglycan binding outer membrane lipoprotein RmpM in Neisseria that also reduced the formation of larger complexes of TBDTs.

scholarly journals 1467. Association between Pathogen Load in the Upper Respiratory Tract and Severe Acute Respiratory Infections in Guatemalan Adults: Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pneumoniae, Klebsiella pneumoniae

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S735-S736
Author(s):  
Sarah Hamid ◽  
Jennifer Milucky ◽  
Nong Shang ◽  
Bernard Wolff ◽  
Chris Van Beneden ◽  
...  
Keyword(s):  
Moraxella Catarrhalis ◽  
Respiratory Infections ◽  
Bacterial Pathogen ◽  
Acute Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Similar Frequency ◽  
Pathogen Load ◽  
Severe Acute Respiratory Infections ◽  
Upper Respiratory

Abstract Background The causal attribution of bacterial pathogens to severe acute respiratory infections (SARI) is challenging because many bacteria are frequently detected in the upper respiratory tract of asymptomatic persons. Quantification of pathogen load may help differentiate asymptomatic pathogen carriage from clinically significant infection. We aimed to determine whether real-time PCR (rt-PCR) cycle threshold (Ct) values, as a proxy for bacterial load, differ between adults with SARI and asymptomatic adults. Methods Adults with SARI (acute onset of fever and cough, requiring hospitalization) were frequency matched to asymptomatic adults (enrolled from trauma and orthopedic inpatient wards) by age group, catchment area, and enrollment date at three surveillance sites in Guatemala. Nasopharyngeal and oropharyngeal specimens were collected from all participants and tested for pathogens using rt-PCR. Using the Wilcoxon rank sum test, we compared the distributions and median Ct values between ill and asymptomatic adults in whom Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pneumoniae, and Klebsiella pneumoniae were detected. Results Between October 2013 and October 2015, 304 adults with SARI and 174 asymptomatic adults were enrolled (Table). M. catarrhalis, S. aureus, and S. pneumoniae were detected with similar frequency in both groups. H. influenzae and K. pneumoniae were detected more frequently in asymptomatic adults. We found the greatest difference in Ct value distributions between ill (median Ct=30.8) and asymptomatic adults (median Ct=35.6) with S. pneumoniae detections (p< 0.01) (Figure). Median Ct values of H. influenzae (29.3 vs 31.1, p=0.04) and M. catarrhalis (29.2 vs 31.5, p=0.05) were also lower among adults with SARI. Frequency of select bacterial pathogen detection among adults with SARI and among asymptomatic adults, Guatemala, 2013-2015 Distributions of Ct values among adults with SARI and asymptomatic adults in whom a given bacterial pathogen was detected Conclusion Pathogen loads of S. pneumoniae, H. influenzae, and M. catarrhalis were higher among adults with SARI than among asymptomatic adults, suggesting that Ct values may provide insight into SARI etiology for some pathogens, despite the similar frequency of detection among both ill and asymptomatic adults. Future work will normalize Ct values to account for variation in testing and analysis and explore the use of Ct values to estimate population attributable fractions of respiratory infections. Disclosures All Authors: No reported disclosures

scholarly journals Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magen E. Francis ◽  
Brian Richardson ◽  
Una Goncin ◽  
Mara McNeil ◽  
Melissa Rioux ◽  
...  
Keyword(s):  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Age Bias ◽  
Antiviral Responses ◽  
Male Sex ◽  
Upper Respiratory ◽  
Interferon Responses ◽  
The Impact ◽  
Insight Into ◽  
Older Males

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

scholarly journals AB1240 C4B BINDING PROTEIN AND WARFARIN IN THE ANTIPHOSPHOLIPID SYNDROME

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1911.2-1911
Author(s):  
G. Grosso ◽  
K. Sandholm ◽  
I. Gunnarsson ◽  
A. Zickert ◽  
A. Vikerfors ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Mediation Analysis ◽  
Binding Protein ◽  
Protein A ◽  
Protein S ◽  
Protein Isoforms ◽  
Type I ◽  
Complement Inhibitor ◽  
Warfarin Treatment ◽  
The Impact

Background:Complement plays a role in the Antiphospholipid Syndrome (APS). C4b Binding Protein (C4BP) is a complement inhibitor with anticoagulant function (1). It belongs to the same protein family as β2GPI, the main antigen in APS. Its main isoform is bound to protein S in the circulation. Levels of both protein S and C4BP are known to be reduced by warfarin treatment (2) as well as by aPL, directly and indirectly.Objectives:To investigate the levels of C4BP in primary (p) and secondary (s) APS, also considering warfarin treatment.Methods:The total amount of C4BP (C4BPt) was measured by using magnetic carboxylated microspheres which were coupled with a monoclonal antibody against the α-chain of human-C4BP to capture the antigen. To detect C4BPt the same antibody was used, biotinylated. The binding of biotinylated antibodies was detected by streptavidin-phycoerythrin and data were collected using a MAGPIX Multiplex Reader. Using independent t-test, we compared C4BP in 118 SLE patients with repeated positivity for Antiphospholipid antibodies (aPL) (39/118 on warfarin), 291 aPL negative SLE patients (16/291 on warfarin), 67 pAPS (33/67 on warfarin), and 322 controls (none on warfarin). We then performed an interaction and a mediation analysis (3) in the SLE group to study the impact of warfarin on C4BP levels: since warfarin is mostly prescribed to aPL+ patients, it is considered a mediator in the reducing effect of aPL on C4BP. Therefore we compared individuals exposed and non-exposed to the presence of aPL with or without the mediator warfarin and calculated the percentage of reduction in C4BP that could be attributed to aPL or warfarin.Results:Overall C4BP is 20% reduced in aPL+ patients (fig 1), independently of SLE, past thrombotic events and nephritis. Warfarin treated patients have lower levels of C4BP (fig 2). According to mediation analysis 11% of C4BP reduction is due to aPL and 9% to warfarin.Figure 1.C4BP in different subgroups (67 pAPS, 118 SLEaPL+, 291 SLEaPL-, 322 controls)Figure 2.C4BP in 67 pAPS patients, 33/67 on warfarinConclusion:Both aPL and warfarin decrease levels of C4BP, a complement and coagulation regulator. Reduction of this complement inhibitor could contribute to complement activation and thrombosis in APS. Our results raise new questions regarding the effects of warfarin treatment on complement and coagulation in APS.References:[1]Dahlbäck B. C4b-binding protein: a forgotten factor in thrombosis and hemostasis. Seminars in thrombosis and hemostasis 2011; 37(4): 355.[2]Zöller B, García de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85(12): 3524.[3]Vanderweele TJ, Vansteelandt S. Conceptual issues concerning mediation, interventions and composition. Statistics and Its Interface 2009; 2(4): 457-68.Disclaimer:AV is employed at the Swedish Medical Products Agency, the views expressed in this paper are the personal views of the authors and not necessarily the views of the Governement AgencyAcknowledgments:Thanks to the Biostatistics Core Facility, Karolinska UniversityDisclosure of Interests:None declared

scholarly journals Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial

2019 ◽  
Author(s):  
Larissa May ◽  
Grant Tatro ◽  
Eduard Poltavskiy ◽  
Benjamin Mooso ◽  
Simson Hon ◽  
...  
Keyword(s):  
Emergency Department ◽  
Length Of Stay ◽  
Usual Care ◽  
Controlled Trial ◽  
Antibiotic Use ◽  
Respiratory Pathogens ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Tract Infections ◽  
The Impact

Abstract Background Acute upper respiratory tract infections are a common cause of Emergency Department (ED) visits and often result in unnecessary antibiotic treatment.  Methods We conducted a randomized clinical trial to evaluate the impact of a rapid, multi-pathogen respiratory panel (RP) test versus usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136). Results Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (p=0.0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (-12% [95% CI -25%, 0.4%]; p=0.06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (-19%) versus adults (-9%; post-hoc analysis). There was no difference in antiviral use, length of stay, or disposition. Conclusions Rapid RP testing was associated with a trend towards decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.

scholarly journals Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng Lei ◽  
Lisong Yang ◽  
Cheong Tat Lou ◽  
Fan Yang ◽  
Kin Ian SiTou ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Viral Etiology ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper Respiratory Tract Infections

PEDIATRICS ◽  
1998 ◽  
Vol 101 (Supplement_1) ◽  
pp. 163-165 ◽  
Author(s):  
Scott F. Dowell ◽  
S. Michael Marcy ◽  
William R. Phillips ◽  
Michael A. Gerber ◽  
Benjamin Schwartz
Keyword(s):  
Respiratory Tract ◽  
Antimicrobial Agents ◽  
Respiratory Infections ◽  
The United States ◽  
Antimicrobial Treatment ◽  
Antimicrobial Use ◽  
Upper Respiratory Tract ◽  
Oral Agents ◽  
Upper Respiratory ◽  
Tract Infections

This article introduces a set of principles to define judicious antimicrobial use for five conditions that account for the majority of outpatient antimicrobial use in the United States. Data from the National Center for Health Statistics indicate that in recent years, approximately three fourths of all outpatient antibiotics have been prescribed for otitis media, sinusitis, bronchitis, pharyngitis, or nonspecific upper respiratory tract infection.1Antimicrobial drug use rates are highest for children1; therefore, the pediatric age group represents the focus for the present guidelines. The evidence-based principles presented here are focused on situations in which antimicrobial therapy could be curtailed without compromising patient care. They are not formulated as comprehensive management strategies. For most upper respiratory infections that require antimicrobial treatment, there are several appropriate oral agents from which to choose. Although the general principles of selecting narrow-spectrum agents with the fewest side effects and lowest cost are important, the principles that follow include few specific antibiotic selection recommendations.

Medical Consultations After Typhoon Haiyan in a Field Hospital in the Philippines

2019 ◽  
Vol 14 (1) ◽  
pp. 34-38
Author(s):  
Julita Gil Cuesta ◽  
Joris Adriaan Frank van Loenhout ◽  
Maria Lourdes de Lara Banquesio ◽  
Masniza Mustaffa ◽  
Debarati Guha-Sapir
Keyword(s):  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
District Hospital ◽  
The Philippines ◽  
Upper Respiratory Tract ◽  
Field Hospital ◽  
Adult Men ◽  
Medical Consultations ◽  
Upper Respiratory ◽  
Tract Infections

ABSTRACTIntroduction and Objectives:Typhoon Haiyan partially destroyed the Ormoc District Hospital in the Philippines. A field hospital was established to replace its outpatient department for 5 weeks. We investigated the reasons for medical consultation in the field hospital.Methods:We described the consultations by sex, age, week, and diagnosis according to the Surveillance in Post-Extreme Emergencies and Disasters system. We compared the number and proportion of upper respiratory tract infections (URTIs) with a control season in 2014.Results:We included 6785 consultations, 55.9% from women. The majority of consultations were communicable diseases (88.2%) followed by noncommunicable (7.1%) and injuries (5.6%). Males suffered more often from injuries than women (66.0% vs 34.0%). Consultations due to injuries decreased from 10.0% in the first to 2.9% in the last week. The most frequent diagnosis over the study period was acute respiratory infections (ARIs) (73.1%), of which 83.0% were children. The number of daily URTIs was higher than in a similar 2014 period.Conclusions:ARI was the most prevalent diagnosis. We recommend ARI treatments being fully accessible after such a disaster. During the first week, injury prevention should focus on adult men. Studies after natural disasters should include control periods to better understand disease distribution, ultimately improving the prioritization in disasters.

Diseases Due to Chlamydiaceae

2013 ◽  
Author(s):  
Walter E Stamm
Keyword(s):  
Sexually Transmitted Diseases ◽  
Respiratory Infections ◽  
Close Contact ◽  
Mammalian Species ◽  
Perinatal Transmission ◽  
Upper Respiratory Tract ◽  
Sexually Transmitted ◽  
Obligate Intracellular ◽  
Upper Respiratory ◽  
Obligate Intracellular Bacteria

The Chlamydiaceae are obligate intracellular bacteria that produce a wide variety of infections in many mammalian and avian species. Three species belonging to two genera of Chlamydiaceae infect humans: Chlamydia trachomatis, Chlamydophila psittaci, and Chlamydophila pneumoniae. C. trachomatis is exclusively a human pathogen and is transmitted from person to person via sexual contact, perinatal transmission, or close contact in households. C. psittaci, in contrast, is more widely distributed in nature, producing genital, conjunctival, intestinal, or respiratory infections in many avian and mammalian species. C. pneumoniae is a fastidious organism that produces upper respiratory tract infection and pneumonitis in both children and adults. This chapter details the epidemiology, pathogenesis, diagnosis, and treatment of chlamydial diseases. Sexually transmitted diseases, perinatal infections, adult inclusion conjunctivitis, trachoma, and psittacosis are covered. The chapter also includes tables outlining comparative features of the three species and treatment of sexually transmitted diseases caused by C. trachomatis, as well as a figure illustrating the life cycle of Chlamydiaceae.  This review contains 1 highly rendered figure, 2 tables, and 87 references.

Bacterial Infections of the Adult Upper Respiratory Tract

2019 ◽  
Author(s):  
Laura K Certain ◽  
Miriam B Barshak
Keyword(s):  
Respiratory Tract ◽  
Bacterial Infections ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Group A Streptococcus ◽  
The United States ◽  
Controlled Study ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Tract Infections

Upper respiratory tract infections are the most common maladies experienced by humankind.1 The majority are caused by respiratory viruses. A Dutch case-controlled study of primary care patients with acute respiratory tract infections found that viruses accounted for 58% of cases; rhinovirus was the most common (24%), followed by influenza virus type A (11%) and corona­viruses (7%). Group A streptococcus (GAS) was responsible for 11%, and 3% of patients had mixed infections. Potential pathogens were detected in 30% of control patients who were free of acute respiratory symptoms; rhinovirus was the most common.2 Given the increasing problem of antibiotic resistance and the increasing awareness of the importance of a healthy microbiome, antibiotic use for upper respiratory infections should be reserved for those patients with clear indications for treatment. A recent study of adult outpatient visits in the United States found that respiratory complaints accounted for 150 antibiotic prescriptions per 1,000 population annually, yet the expected “appropriate” rate would be 45.3 In other words, most antibiotic prescriptions for these complaints are unnecessary. Similarly, a study in the United Kingdom found that general practitioners prescribed antibiotics to about half of all patients presenting with an upper respiratory infection, even though most of these infections are viral.4 This review contains 5 figures, 16 tables, and 82 references. Keywords: infection, airway, sinusitis, otitis media, otitis externa, pharyngitis, epiglottitis, abscess

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