scholarly journals Nonpneumococcal Strains Recently Recovered from Carriage Specimens and Expressing Capsular Serotypes Highly Related or Identical to Pneumococcal Serotypes 2, 4, 9A, 13, and 23A

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Robert E. Gertz ◽  
Fabiana C. Pimenta ◽  
Sopio Chochua ◽  
Shanda Larson ◽  
Anne-Kathryn Venero ◽  
...  
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
The United States ◽  
Upper Respiratory Tract ◽  
Pneumococcal Serotypes ◽  
Content Type ◽  
Commensal Species ◽  
Streptococcus Oralis ◽  
Pneumococcal Serotype ◽  
Upper Respiratory

ABSTRACT The polysaccharide capsule is a key virulence factor of Streptococcus pneumoniae. There are numerous epidemiologically important pneumococcal capsular serotypes, and recent findings have demonstrated that several of them are commonly found among nonpathogenic commensal species. Here, we describe 9 nonpneumococcal strains carrying close homologs of pneumococcal capsular biosynthetic (cps) loci that were discovered during recent pneumococcal carriage studies of adults in the United States and Kenya. Two distinct Streptococcus infantis strains cross-reactive with pneumococcal serotype 4 and carrying cps4-like capsular biosynthetic (cps) loci were recovered. Opsonophagocytic killing assays employing rabbit antisera raised against S. infantis US67cps4 revealed serotype 4-specific killing of both pneumococcal and nonpneumococcal strains. An S. infantis strain and two Streptococcus oralis strains, all carrying cps9A-like loci, were cross-reactive with pneumococcal serogroup 9 strains in immunodiffusion assays. Antiserum raised against S. infantis US64cps9A specifically promoted killing of serotype 9A and 9V pneumococcal strains as well as S. oralis serotype 9A strains. Serotype-specific PCR of oropharyngeal specimens from a recent adult carriage study in the United States indicated that such nonpneumococcal strains were much more common in this population than serotype 4 and serogroup 9 pneumococci. We also describe S. oralis and S. infantis strains expressing serotypes identical or highly related to serotypes 2, 13, and 23A. This study has expanded the known overlap of pneumococcal capsular serotypes with related commensal species. The frequent occurrence of nonpneumococcal strains in the upper respiratory tract that share vaccine and nonvaccine capsular serotypes with pneumococci could affect population immunity to circulating pneumococcal strains. IMPORTANCE The distributions and frequencies of individual pneumococcal capsular serotypes among nonpneumococcal strains in the upper respiratory tract are unknown and potentially affect pneumococcal serotype distributions among the population and immunity to circulating pneumococcal strains. Repeated demonstration that these nonpneumococcal strains expressing so-called pneumococcal serotypes are readily recovered from current carriage specimens is likely to be relevant to pneumococcal epidemiology, niche biology, and even to potential strategies of employing commensal live vaccines. Here, we describe multiple distinct nonpneumococcal counterparts for each of the pneumococcal conjugate vaccine (PCV) serotypes 4 and 9V. Additional data from contemporary commensal isolates expressing serotypes 2, 13, and 23A further demonstrate the ubiquity of such strains. Increased focus upon this serological overlap between S. pneumoniae and its close relatives may eventually prove that most, or possibly all, pneumococcal serotypes have counterparts expressed by the common upper respiratory tract commensal species Streptococcus mitis, Streptococcus oralis, and Streptococcus infantis.

scholarly journals Conservation of Meningococcal Antigens in the Genus Neisseria

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Alessandro Muzzi ◽  
Marirosa Mora ◽  
Mariagrazia Pizza ◽  
Rino Rappuoli ◽  
Claudio Donati
Keyword(s):  
Bacterial Meningitis ◽  
Respiratory Tract ◽  
Neisseria Meningitidis ◽  
Recombination Event ◽  
Factor H ◽  
High Rate ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Commensal Species ◽  
Upper Respiratory

ABSTRACTNeisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genusNeisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), andN. meningitidisadhesin A (NadA), have been described as antigens protective againstN. meningitidisof serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genusNeisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 fromN. cinereawas introduced intoN. meningitidisby a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists.IMPORTANCEThe upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genusNeisseria, includingNeisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine againstN. meningitidishas the potential to impact the other commensal species ofNeisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.

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.

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

scholarly journals Identification of Pneumococcal Factors Affecting Pneumococcal Shedding Shows that thedltLocus Promotes Inflammation and Transmission

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
M. Ammar Zafar ◽  
Alexandria J. Hammond ◽  
Shigeto Hamaguchi ◽  
Weisheng Wu ◽  
Masamitsu Kono ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Capsular Polysaccharide ◽  
Inflammatory Responses ◽  
Transposon Mutagenesis ◽  
Respiratory Pathogen ◽  
Invasive Infection ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Upper Respiratory

ABSTRACTHost-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogenStreptococcus pneumoniaegenerated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was thedltlocus, which addsd-alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence ofd-alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of thedltlocus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in alysM−/−host, there was no longer an effect of thedltlocus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host.IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiasedin vivotransposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by thedltlocus, previously shown to addd-alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.

scholarly journals Rhinoscleroma with Pharyngolaryngeal Involvement Caused byKlebsiella ozaenae

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
J. Gonzales Zamora ◽  
A. R. Murali
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Central America ◽  
United States Of America ◽  
Upper Airway ◽  
The United States ◽  
Upper Respiratory Tract ◽  
The Usa ◽  
Upper Respiratory ◽  
Histopathology Examination

Rhinoscleroma is a chronic, slowly progressive granulomatous bacterial infection that is endemic to the tropical world, namely, Central America and Africa. It is occasionally seen in the United States of America (USA). It predominately affects the nasal mucosa but can also involve the rest of the upper respiratory tract. The well-known causative agent for rhinoscleroma is the bacteriumKlebsiella rhinoscleromatis, a subspecies ofKlebsiella pneumoniae. However,Klebsiella ozaenaecan also, albeit very rarely, cause rhinoscleroma. The diagnosis is confirmed by histopathology examination that shows the characteristic Mikulicz cells, considered pathognomonic for this infection. We report a patient with histologically proven rhinoscleroma with pharyngolaryngeal involvement in whom cultures yieldedKlebsiella ozaenae. To the best of our knowledge, only two cases of rhinoscleroma due toKlebsiella ozaenaehave been reported in the literature to date. Our case illustrates the importance of recognizing this infection in a nonendemic setting such as the USA. A lack of awareness and a delay in the diagnosis of this disease can lead to complications including upper airway obstruction, physical deformity, and, rarely, sepsis. In addition, it must be remembered that the treatment of rhinoscleroma is challenging and requires a prolonged course of antibiotics to achieve a definite cure and avoid relapses.

scholarly journals Type I Interferon Signaling Is a Common Factor Driving Streptococcus pneumoniae and Influenza A Virus Shedding and Transmission

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tonia Zangari ◽  
Mila B. Ortigoza ◽  
Kristen L. Lokken-Toyli ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Common Factor ◽  
Type I ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Infant Mouse ◽  
Upper Respiratory

ABSTRACT The dynamics underlying respiratory contagion (the transmission of infectious agents from the airways) are poorly understood. We investigated host factors involved in the transmission of the leading respiratory pathogen Streptococcus pneumoniae. Using an infant mouse model, we examined whether S. pneumoniae triggers inflammatory pathways shared by influenza A virus (IAV) to promote nasal secretions and shedding from the upper respiratory tract to facilitate transit to new hosts. Here, we show that amplification of the type I interferon (IFN-I) response is a critical host factor in this process, as shedding and transmission by both IAV and S. pneumoniae were decreased in pups lacking the common IFN-I receptor (Ifnar1−/− mice). Additionally, providing exogenous recombinant IFN-I to S. pneumoniae-infected pups was sufficient to increase bacterial shedding. The expression of IFN-stimulated genes (ISGs) was upregulated in S. pneumoniae-infected wild-type (WT) but not Ifnar1−/− mice, including genes involved in mucin type O-glycan biosynthesis; this correlated with an increase in secretions in S. pneumoniae- and IAV-infected WT compared to Ifnar1−/− pups. S. pneumoniae stimulation of ISGs was largely dependent on its pore-forming toxin, pneumolysin, and coinfection with IAV and S. pneumoniae resulted in synergistic increases in ISG expression. We conclude that the induction of IFN-I signaling appears to be a common factor driving viral and bacterial respiratory contagion. IMPORTANCE Respiratory tract infections are a leading cause of childhood mortality and, globally, Streptococcus pneumoniae is the leading cause of mortality due to pneumonia. Transmission of S. pneumoniae primarily occurs through direct contact with respiratory secretions, although the host and bacterial factors underlying transmission are poorly understood. We examined transmission dynamics of S. pneumoniae in an infant mouse model and here show that S. pneumoniae colonization of the upper respiratory tract stimulates host inflammatory pathways commonly associated with viral infections. Amplification of this response was shown to be a critical host factor driving shedding and transmission of both S. pneumoniae and influenza A virus, with infection stimulating expression of a wide variety of genes, including those involved in the biosynthesis of mucin, a major component of respiratory secretions. Our findings suggest a mechanism facilitating S. pneumoniae contagion that is shared by viral infection.

scholarly journals Pathogenesis and Transmission of Genetically Diverse Swine-Origin H3N2 Variant Influenza A Viruses from Multiple Lineages Isolated in the United States, 2011–2016

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Xiangjie Sun ◽  
Joanna A. Pulit-Penaloza ◽  
Jessica A. Belser ◽  
Claudia Pappas ◽  
Melissa B. Pearce ◽  
...  
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Influenza A ◽  
Seasonal Influenza ◽  
The United States ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Pandemic Preparedness

ABSTRACTWhile several swine-origin influenza A H3N2 variant (H3N2v) viruses isolated from humans prior to 2011 have been previously characterized for their virulence and transmissibility in ferrets, the recent genetic and antigenic divergence of H3N2v viruses warrants an updated assessment of their pandemic potential. Here, four contemporary H3N2v viruses isolated during 2011 to 2016 were evaluated for their replicative ability in bothin vitroandin vivoin mammalian models as well as their transmissibility among ferrets. We found that all four H3N2v viruses possessed similar or enhanced replication capacities in a human bronchial epithelium cell line (Calu-3) compared to a human seasonal influenza virus, suggestive of strong fitness in human respiratory tract cells. The majority of H3N2v viruses examined in our study were mildly virulent in mice and capable of replicating in mouse lungs with different degrees of efficiency. In ferrets, all four H3N2v viruses caused moderate morbidity and exhibited comparable titers in the upper respiratory tract, but only 2 of the 4 viruses replicated in the lower respiratory tract in this model. Furthermore, despite efficient transmission among cohoused ferrets, recently isolated H3N2v viruses displayed considerable variance in their ability to transmit by respiratory droplets. The lack of a full understanding of the molecular correlates of virulence and transmission underscores the need for close genotypic and phenotypic monitoring of H3N2v viruses and the importance of continued surveillance to improve pandemic preparedness.IMPORTANCESwine-origin influenza viruses of the H3N2 subtype, with the hemagglutinin (HA) and neuraminidase (NA) derived from historic human seasonal influenza viruses, continue to cross species barriers and cause human infections, posing an indelible threat to public health. To help us better understand the potential risk associated with swine-origin H3N2v viruses that emerged in the United States during the 2011-2016 influenza seasons, we use bothin vitroandin vivomodels to characterize the abilities of these viruses to replicate, cause disease, and transmit in mammalian hosts. The efficient respiratory droplet transmission exhibited by some of the H3N2v viruses in the ferret model combined with the existing evidence of low immunity against such viruses in young children and older adults highlight their pandemic potential. Extensive surveillance and risk assessment of H3N2v viruses should continue to be an essential component of our pandemic preparedness strategy.

Sign in / Sign up

Export Citation Format

Share Document