Streptococcus pneumoniae Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies

Abstract

Purpose of ReviewThis study aimed to review the literature regarding the mechanisms of transition from asymptomatic colonization to induction of otitis media and how the insight into the pathogenesis of otitis media has the potential to help design future otitis media-directed vaccines.Recent FindingsRespiratory viruses have long been shown to predispose individuals to bacterial respiratory infections, such as otitis media. Recent information suggests that Streptococcus pneumoniae, which colonize the nasopharynx asymptomatically, can sense potentially “threatening” changes in the nasopharyngeal environment caused by virus infection by upregulating specific sets of genes involved in biofilm release, dissemination from the nasopharynx to other sites, and protection against the host immune system. Furthermore, an understanding of the transcriptional and proteomic changes occurring in bacteria during transition to infection has led to identification of novel vaccine targets that are disease-specific and will not affect asymptomatic colonization. This approach will avoid major changes in the delicate balance of microorganisms in the respiratory tract microbiome due to elimination of S. pneumoniae.SummaryOur recent findings are reviewed in the context of the current literature on the epidemiology and pathogenesis of otitis media. We also discuss how other otopathogens, such as Haemophilus influenzae and Moraxella catarrhalis, as well as the normal respiratory microbiome, can modulate the ability of pneumococci to cause infection. Furthermore, the unsatisfactory protection offered by the pneumococcal conjugate vaccines is highlighted and we review potential future strategies emerging to confer a more specific protection against otitis media.

Treatment of Streptococcus pneumoniae otitis media in a chinchilla model by transtympanic delivery of antibiotics

“…Streptococcus pneumoniae (S. pneumoniae) accounts for 30%-50% of all OM cases, translating to approximately 300 million OM cases worldwide annually (20). Reduced susceptibility or resistance to β-lactam and macrolide antibiotics is prevalent among isolates of S. pneumoniae (21,22).…”

The LuxS/AI-2 Quorum-Sensing System of Streptococcus pneumoniae Is Required to Cause Disease, and to Regulate Virulence- and Metabolism-Related Genes in a Rat Model of Middle Ear Infection

“…More than 80% of children up to the age of 3 year experience at least one episode of acute OM (AOM), and the health and economic burdens associated with AOM are significant (Pichichero, 2013 ; Usonis et al, 2016 ). Streptococcus pneumoniae ( S. pneumoniae ) is the most important bacteria that causes AOM in children (Bergenfelz and Hakansson, 2017 ). Although S. pneumoniae can cause disease, it is a commensal bacterium that quiescently and asymptomatically colonizes the mucosal surface of the nasopharynx in the form of a specialized structure called a biofilm (Bogaert et al, 2004 ; Simell et al, 2012 ).…”

Niche- and Gender-Dependent Immune Reactions in Relation to the Microbiota Profile in Pediatric Patients with Otitis Media with Effusion

“…In patients with an intact tympanic membrane, OM is widely presumed to result from ascension of bacteria from the nasopharynx (NPH) through the Eustachian tube to the ME. This route is supported by the observation that colonization of specific bacteria in the NPH is associated with increased risk of OM, and is possibly even a prerequisite for particular infections (6,7).…”