Biofilm Biology and Vaccine Strategies for Otitis Media Due to Nontypeable Haemophilus influenzae

Abstract

Otitis media (OM) is one of the most common diseases of childhood, and nontypeable Haemophilus influenzae (NTHI) is the predominant causative agent of chronic and recurrent OM, as well as OM for which treatment has failed. Moreover, NTHI is now as important a causative agent of acute OM as the pneumococcus. NTHI colonizes the human nasopharynx asymptomatically. However, upon perturbation of the innate and physical defenses of the airway by upper respiratory tract viral infection, NTHI can replicate, ascend the Eustachian tube, gain access to the normally sterile middle ear space, and cause disease. Bacterial biofilms within the middle ear, including those formed by NTHI, contribute to the chronic and recurrent nature of this disease. These multicomponent structures are highly resistant to clearance by host defenses and elimination by traditional antimicrobial therapies. Herein, we review several strategies utilized by NTHI to persist within the human host and interventions currently under investigation to prevent and/or resolve NTHI-induced diseases of the middle ear and uppermost airway.

Panel 8: Vaccines and immunology

“…As knowledge of OM pathogenesis has advanced and the central role of biofilms in the course of the disease has become recognized, it is clear that middle ear fluid culture, long-considered gold standard for etiological diagnosis, only identifies etiology for a subset of OM. Effusions recovered from the middle ear are often negative by culture but contain abundant, viable bacterial pathogens present in biofilms [3][4][5][6][7][8][9][10]. Bacteria that persist in biofilms have a reduced growth rate, distinct transcriptome, increased resistance to effectors of innate and acquired immunity, and recalcitrance to the action of antimicrobial agents compared to planktonic bacteria.…”

“…As indicated by the difference in number of middle ear fluid samples analyzed since 2012, culture is still the most popular method used to determine OM etiology -despite ample evidence that PCR is more sensitive in detecting pathogens in middle ear fluid (particularly in the case of M. catarrhalis). The difference between culture and PCR results is likely due to the low sensitivity of culture in detecting bacteria in biofilms [4,7,11,12]. Therefore, recognizing the role of biofilms in OM is important for understanding the etiology of OM and in designing rational vaccine development strategies.…”

Reprioritization of biofilm metabolism is associated with nutrient adaptation and long-term survival of Haemophilus influenzae

“…Whole-genome sequencing of an isolate obtained on day 33 (termed RM33) of a long-standing stationary phase culture revealed a single mutation within the icc gene that encodes the only known cAMP phosphodiesterase in NTHI strain 86-028NP. 33 Given the observation that biofilms are an important pathogenic lifestyle of NTHI during OM, 28,34,35 we investigated the role of icc in biofilm formation. The parental strain formed biofilms with a mat-like architecture with a range in overall height of 2.5–55.1 µm (mean = 14.95 ± 9.678) (Fig.…”

Characterisation of the phase-variable autotransporter Lav reveals a role in host cell adherence and biofilm formation in Non-TypeableHaemophilus influenzae

“…The establishment of bacterial biofilms is critical during colonization and disease. Biofilms help bacteria adhere to the mucosal surfaces, and provide increased resistance to host defences and antimicrobials (43)(44)(45). Thus, expression of Lav might provide a selective advantage to NTHi during initial colonisation and establishment at the mucosal surface.…”