Molecular epidemiology of nonencapsulated Streptococcus pneumoniae among Japanese children with acute otitis media

Hotomi, Muneki; Nakajima, Kanako; Hiraoka, Masanobu; Nahm, Moon H.; Yamanaka, Noboru

doi:10.1016/j.jiac.2015.10.006

Cited by 19 publications

(10 citation statements)

References 54 publications

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“…NESp strains have been isolated from children with otitis media (OM) ( 27 , 29 , 124 ). In fact, one study found that as many as 8% of OM isolates were NESp ( 27 ), and, more recently, NESp strains were found in 6.4% of OM isolates ( 125 ). This is interesting because complement hinders pneumococcal infections in the middle ear ( 126 ) and NESp strains lack the protection from complement afforded by the capsule and PspC ( 78 , 107 ).…”

Section: Diseasementioning

confidence: 99%

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

Keller

Robinson

McDaniel

2016

mBio

130

153

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While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulated Streptococcus pneumoniae (NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci.

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Section: Diseasementioning

confidence: 99%

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

Keller

Robinson

McDaniel

2016

mBio

130

153

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“…Although pneumococcal conjugate vaccines (PCV7/PCV13) have had considerable success in reducing the incidences of IPD, they have achieved only modest success with respect to the prevention of otitis media [ 93 ]. Epidemiological reports also suggest increasing prevalence of otitis media infections caused by non-encapsulated S. pneumoniae strains in vulnerable populations [ 26 ]. Antibiotic therapy is the most accepted mode of treatment for otitis media.…”

Section: Pneumococcal Colonisation Of the Respiratory Mucosamentioning

confidence: 99%

“…Recently, a 15-valent pneumococcal conjugate vaccine containing the serotypes in PCV13 and an additional 2 serotypes (22F and 33F) has been developed to address this shift and further curb pneumococcal carriage and invasive disease [ 25 ]. Importantly, recent epidemiological studies suggest there is also a rise in the number of individuals colonised with non-encapsulated S. pneumoniae [ 26 ]. This is presumably driven by both vaccine and antibiotic selective pressures, although increased sensitivity in our detection methods may account for increasing numbers.…”

Section: Introductionmentioning

confidence: 99%

Anatomical site-specific contributions of pneumococcal virulence determinants

Shenoy

Orihuela

2016

pneumonia

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Streptococcus pneumoniae is an opportunistic pathogen globally associated with significant morbidity and mortality. It is capable of causing a wide range of diseases including sinusitis, conjunctivitis, otitis media, pneumonia, bacteraemia, sepsis, and meningitis. While its capsular polysaccharide is indispensible for invasive disease, and opsonising antibodies against the capsule are the basis for the current vaccines, a long history of biomedical research indicates that other components of this Gram-positive bacterium are also critical for virulence. Herein we review the contribution of pneumococcal virulence determinants to survival and persistence in the context of distinct anatomical sites. We discuss how these determinants allow the pneumococcus to evade mucociliary clearance during colonisation, establish lower respiratory tract infection, resist complement deposition and opsonophagocytosis in the bloodstream, and invade secondary tissues such as the central nervous system leading to meningitis. We do so in a manner that highlights both the critical role of the capsular polysaccharide and the accompanying and necessary protein determinants. Understanding the complex interplay between host and pathogen is necessary to find new ways to prevent pneumococcal infection. This review is an attempt to do so with consideration for the latest research findings.

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“…Although the current prevalence of NE S. pneumoniae is still a small percentage of the pneumococci involved in nasopharyngeal carriage, the increase in colonization by these strains increases the risk of AOM. Consequently, NE S. pneumoniae that acts as a reservoir for antibiotic resistance determinants may be considered a newly emerging human pathogen (12,13).…”

mentioning

confidence: 99%

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

Domenech

Garcı́a

2017

Antimicrob Agents Chemother

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Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and nontypeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in the carriage of nonencapsulated S. pneumoniae. Frequently, pneumococci and H. influenzae live together in the human nasopharynx, forming a self-produced biofilm. Biofilms present a global medical challenge since the inherent antibiotic resistance of their producers demands the use of large doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence. Here, we describe the development of an in vitro nonencapsulated S. pneumoniae-nontypeable H. influenzae biofilm system with polystyrene or glass-bottom plates. Confocal laser scanning microscopy and specific fluorescent labeling of pneumococcal cells with Helix pomatia agglutinin revealed an even distribution of both species within the biofilm. This simple and robust protocol of mixed biofilms was used to test the antimicrobial properties of two well-known antioxidants that are widely used in the clinical setting, i.e., N-acetyl-L-cysteine and cysteamine. This repurposing approach showed the high potency of N-acetyl-Lcysteine and cysteamine against mixed biofilms of nonencapsulated S. pneumoniae and nontypeable H. influenzae. Decades of clinical use mean that these compounds are safe to use, which may accelerate their evaluation in humans. KEYWORDS Haemophilus influenzae, Streptococcus pneumoniae, antioxidants, biofilmsA cute otitis media (AOM) is defined as the presence of inflammation in the middle ear accompanied by the rapid onset of signs and symptoms of an ear infection. Frequent suppurative complications of AOM are mastoiditis, hearing loss, and meningitis. AOM is a significant public health problem worldwide (incidence rate, ϳ11%) (1). Indeed, Ͼ80% of children suffer at least one episode of AOM by their third birthday and 40% will suffer six or more recurrences by the age of 7 years (2). Pediatric AOM, which is often treated with antibiotics (56 to 95% of cases, depending on the country) (3), represents a significant health care burden, annually accounting for some $2.88 billion in medical costs in the United States (4). A polymicrobial disease, AOM is typically caused by colonization of the middle ear space by opportunistic bacteria that normally form part of the nasopharyngeal microbiota. The most frequently involved bacterial pathogens are Streptococcus pneumoniae, nontypeable (nonencapsulated) Haemophilus influenzae (NT H. influenzae), and, to a lesser extent, Moraxella catarrhalis and other species (5). Several respiratory viruses may also cause AOM (6).

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Molecular epidemiology of nonencapsulated Streptococcus pneumoniae among Japanese children with acute otitis media

Cited by 19 publications

References 54 publications

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

Anatomical site-specific contributions of pneumococcal virulence determinants

N -Acetyl- l -Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae

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