Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease

Abstract

Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm formation and dispersion will elucidate novel avenues to interfere with the spread of antibiotic resistance and vaccine escape, as well as novel strategies to target the mechanisms involved in induction of pneumococcal disease.

Minimal Peptidoglycan (PG) Turnover in Wild-Type and PG Hydrolase and Cell Division Mutants of Streptococcus pneumoniae D39 Growing Planktonically and in Host-Relevant Biofilms

“…Pneumococcal cells from these biofilms can be used to seed long-term, growing biofilms on live epithelial cells (52). Furthermore, bacteria in the biofilms growing on the fixed or live epithelial cells transition to virulent planktonic cells when the biofilms are exposed to stimuli produced during infections (52,65). We repeated FDAA long-pulsechase-new-labeling experiments with unencapsulated and encapsulated D39 strains growing in biofilms on fixed human epithelial cells ( Fig.…”

“…7). Hakansson and coworkers reported that encapsulated strains of S. pneumoniae, which do not form robust biofilms on abiotic surfaces, form physiologically relevant biofilms when in contact with fixed human respiratory tract epithelial cells (53,65). Pneumococcal cells from these biofilms can be used to seed long-term, growing biofilms on live epithelial cells (52).…”

Interaction between Streptococcus pneumoniae and Staphylococcus aureus in paediatric patients suffering from an underlying chronic disease

“…Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, modifications in the microflora, inflammation or other host assaults trigger active release of pneumococci from biofilms. 26,27 These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and brothgrown, planktonic bacteria, resulting in a significantly increased virulence in vivo. 27 The higher risk of pneumococcal infections, including IPD, in DM1 patients compared with healthy subjects has been well known for many years and was recently confirmed by the observation that, despite the introduction of vaccine prophylaxis, it remained three times higher in the UK than in the general population.…”

“…26,27 These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and brothgrown, planktonic bacteria, resulting in a significantly increased virulence in vivo. 27 The higher risk of pneumococcal infections, including IPD, in DM1 patients compared with healthy subjects has been well known for many years and was recently confirmed by the observation that, despite the introduction of vaccine prophylaxis, it remained three times higher in the UK than in the general population. [28][29][30] Finally, the incidence of staphylococcal infections in DM1 patients is not marginal and some of them can be particularly severe and difficult to treat.…”

Biofilm formation by staphylococci and streptococci: Structural, functional and regulatory aspects and implications for pathogenesis

“…The authors suggest that this may explain long-term, asymptomatic nasopharyngeal colonization by S. pneumoniae in humans. Chao et al (2015) describe the increased propensity of S. pneumoniae in a biofilm to exchange genetic material. Mechanisms involved in dispersal during colonization and disease are also considered.…”