The Regulatory Role of Respiratory Tract Normal Flora (Corynebacterium spp) on Streptococcus pneumoniae Infections

Abstract

Respiratory tract infections (RTIs) pose severe threats to global health. The microbial profile of the respiratory tract largely impacts their ecological niche. Epidemiological studies indicate that nasopharyngeal colonization of commensals like Corynebacterium spp is associated with reduced rates of RTIs, but the underlying mechanisms are undefined. Besides, most pathogens like Streptococcus pneumoniae asymptomatically colonize the mucosa of healthy individuals by forming biofilms. However, in response to extrinsic reasons, such as concomitant virus infections, bacteria disseminate from the biofilms, leading to a transition from asymptomatic carriage to disease/infection.

Here, we studied the commensal-host and commensal-pathogen-host interactions between two clinical corynebacterial isolates Corynebacterium propinquum and Corynebacterium pseudodiptheriticum with the pathogen Streptococcus pneumoniae. By standardizing the single-species biofilm formation and assessment through antibiotic sensitivity assay and Scanning Electron Microscopy, we concluded that an epithelial substratum (live or pre-fixed) encourages the formation of mature, finely structured and consolidated corynebacteria biofilms, instead of abiotic surfaces, thereby contributing to its mutualistic relation with the host. Upon inclusion of pathogenic pneumococci in this system, we further demonstrated that in in vitro dual-species interaction models, corynebacteria reflect a somewhat protective property towards pneumococcus. We also investigated the host inflammatory responses (by studying NFκB and ERK signalling pathways) to corynebacteria alone and in combination with the pneumococcus, but due to experimental limitations were unable to annotate a conclusive remark on the inflammatory sensitization (if any) by corynebacteria on the epithelial cells for the immunomodulation of successive pneumococcus stimulations.

A better understanding of the microbe-microbe and host-microbe interplay responsible for maintaining the nasopharyngeal microbial homeostasis is required to combat severe RTIs and withstand the ever-increasing antibiotic resistance. Thus, novel means of therapeutics can be identified by exploiting the modulatory role of corynebacteria on pneumococcus invasions by either protecting the host against colonization of pathogens or by improving the inflammatory response against pathogens invasions.

Popular Abstract

Corynebacteria: Our friend or foe in Pneumococcus infections?

Have you ever wondered why your grandma said “The way to one’s heart is through his stomach”? Doesn’t that sound silly? But indeed, the inhabitants of our gut microbiome (i.e., all microorganisms present in an ecological niche; normal flora as well as potential pathogens) affect the brain and behaviour thereby regulating our feel-good hormones, improving our mood, motivation and concentration, calming the nervous system and switches off stress reactions. Likewise, the habitation of specific residents of the respiratory tract normal flora correlates with microbiota stability of the respiratory tract and its changes over time. This provides insights into our susceptibility toward the acquisition of symptomatic respiratory infectious diseases, but the mechanism remains unclear. And yes, you guessed it right! This is exactly what we are interested to look at, how Corynebacteria, a well-known respiratory tract commensal can modulate pneumococcus infections.

For those who are still doubting why on earth we need to study this, it’s because respiratory tract infections (RTIs) cause significant mortality and morbidity worldwide and thus pose a major threat to human health. Despite there having been an impressive increase in vaccination and antimicrobial therapy in the last few decades, lower RTIs (most commonly caused by Streptococcus pneumoniae) alone are still responsible for 3-4 million deaths annually.

Like most other opportunistic pathogens, S. pneumoniae first colonizes the nasopharynx asymptomatically by forming biofilms (complex bacterial communities that are resistant to antibiotics). Under certain conditions, usually caused by viral infections or virus-induced changes to the host environment, bacteria can be released from these biofilms and spread from the nasopharynx and cause infection at distant sites, such as the sinuses, middle ears, lungs, brain, the blood resulting in sinusitis, otitis media, pneumonia, meningitis, sepsis etc. However, the underlying mechanisms of the transition from colonization to disease are not well described.

Nevertheless, epidemiological reports indicate that the respiratory tract’s normal flora positively impacts respiratory health. We hypothesize that protective species from the normal flora (like Corynebacteria) could either directly compete with pneumococci in the colonizing niche or could “train” or improve the host immune system and eradicate the pathogen from human carriers. Here, we evaluate the commensal-pathogen-host interactions on the regulatory influence of the respiratory tract normal floras Corynebacterium pseudodiptheriticum and Corynebacterium propinquum on S. pneumoniae behaviour through studying in vitro single-species and dual-species biofilm formation and assessment and host inflammatory responses.

A better understanding of the microbe-microbe and host-microbe interplay responsible for maintaining the nasopharyngeal microbial homeostasis is direly required to combat severe RTIs and withstand the ever-increasing antibiotic resistance. Thus, this study has the potential to contribute to finding novel means of prevention or treatment, thereby laying a future foundation to determine whether habitat modification by Corynebacteria could be exploited for pathogen control and hold promise for clinical application as probiotics against RTIs including pneumococcus invasions.

Master’s Degree Project in Molecular Biology, with Microbiology specialization, 60 credits, 2022
Department of Biology, Faculty of Science, Lund University

Advisor: Prof. Anders P Hakansson
Department of Translational Medicine, Division of Experimental Infection Medicine, Lund University, Malmo

• author: Dutta, Shritama
• supervisor: Anders P Håkansson
• organization: Degree Projects in Molecular Biology
• course: MOBN03 20212
• year: 2022
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9100025
• date added to LUP: 2022-09-13 11:46:42
• date last changed: 2022-09-13 11:46:42