Analytical Essay on Cystic Fibrosis: Gene Mutations and Role of Mucins in Infection

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It is one of the most common genetic disorders in Caucasians. A defective gene and its protein product cause the body to produce a very thick mucus that clogs the lungs and can lead to life-threatening infections. It also obstructs the pancreas and stops natural enzymes from helping the body to break down and absorb food. It’s caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). (Davies, Alton and Bush, 2007) Ireland has the highest incidence of CF in the world. Symptoms of CF include very salty- tasting skin, a persistent cough, frequent lung infections, wheezing or shortness of breath, poor growth or weight gain in spite of a good appetite and frequent greasy, bulky stools or difficulty in bowel movements. (Byrne, Heffernan, & Tallon, 2019)

Mucosal tissue represents the site of infection in human diseases. Mucins are glycoprotein constituents on mucous. Mucins give mucous its gel like structure. Gel-forming mucins are the primary macromolecular components of airway mucus, they assist in airway clearance by mucociliary transport. In CF altered mucus properties impair mucociliary transport. The main gel-forming mucins in the airways are MUC5B and MUC5AC. (Lillehoj, 2017)

The key bacterial agent of CF lung infection is Pseudomonas aeruginosa. P. aeruginosa is the most important pathogen in progressive and severe CF lung disease. Patients are often exposed to this in hospitals and other healthcare settings. P. aeruginosa infections tend to set in after the lung airways are clogged by mucoid secretions. This reduces mucociliary clearance of inhaled microbes, this leads to the formation of bacterial biofilms with mucoid layers as their habitat. Once biofilms are formed, inflammation occurs, in some cases this leads to chronic infection. (Silva, 2019)

P. aeruginosa is a common pathogen found in CF. This is primarily due to the overabundance of mucus in CF airways which causes the perfect environment for P. aeruginosa to thrive in. The mucins found in CF airways are also heavily sialylated which allows P. aeruginosa to bind to them in the first place. The level of glycosylation of mucins directly correlates with the severity of infection in CF patients.(Jeffries et al., 2016)

Main Body

Cystic Fibrosis

Cystic Fibrosis is the most common life limiting autosomal recessive condition in Caucasians. Cystic fibrosis is a complex multi system disease. It affects the lungs, liver, pancreas, intestine, sinuses, bones and the male reproductive tract, however the majority of morbidity and mortality is associated with respiratory disease. Early detection of CF is vital. Improved diagnosis and symptomatic treatment have improved both the health and life span of people suffering with this disease. (Naehrig, Chao and Naehrlich, 2017) Improved diagnosis and symptomatic treatment have improved the health and survival prospects in CF patients. In the 1950s, the average life span of a person with CF was only a few months. Today, because of improved diagnosis and treatments the average life span has increased to 40 years. New-born screening detects cystic fibrosis. (Naehrig, Chao and Naehrlich, 2017)

Gene mutations in Cystic Fibrosis

CF is caused by a mutation in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Conductance is the ability of fluid to pass through the cell membrane. (Antoniou, 2016). The CFTR gene is located on the long arm of chromosome 7. Its main function is to regulate the movement of chloride, it’s also involved in sodium bicarbonate and water transport. A dysfunctional CFTR protein in the airway epithelial will cause the chloride secretion to become impaired. Increased sodium and water reabsorption combined with a reduction in chloride secretion compromises mucociliary clearance efficiency, which is the first line of defense in the respiratory system against pathogens. (Elborn and Vallieres, 2014)

A mutation in both copies of the gene is necessary in order for the disease to be present. The patient must inherit two copies of the CFTR gene that contains the mutation, one copy from each parent. Therefor each parent will either have Cystic fibrosis or they will be a carrier of the CFTR gene mutation.

In those without the mutation, the CFTR protein is produced normally, it reaches the cell surface and becomes an open channel for chloride ions to pass through. There has been over 1700 mutations in the CFTR gene identified, some are common while others are only found in a few people. The most common mutation of the CFTR gene is the Delta F508 mutation. This mutation results in the misfolding of the CFTR protein, which prevents it from moving to the cell surface. The mutant CFTR protein needs a corrector drug to boost it to the surface, it also requires a doorman drug to open the channel so that chloride ions can pass through. Another mutation, which is less common, is the G551D mutation. This differs to the delta F508 mutation as the CTFR protein is created and moves to the cell surface, however the channel does not open properly, and chloride ions cannot pass through.(Meng et al., 2017)

Figure 1 CFTR mutations (Lopes-Pacheco, 2016)

General Role of Mucins in Infection

Mucus has a gel like property which depends primarily on its content of mucins. Mucin genes encode the protein backbone of mucins. There are currently 20 mucin genes that encode the backbone of mucin proteins, 16 of these mucin genes have been identified in the airways. Mucus can be altered by primary mucus disorders, infections, some genetic abnormalities and drugs. Disease related alterations in posttranslational modification of mucins may contribute to the pathology of Cystic Fibrosis. In order to generate a clear profile of mucin expression patterns in health and disease different variables must be analyzed, this can alter the expression. Understanding the various molecular mechanisms in controlling mucin gene and protein expression is essential as it could lead to the invention of novel therapeutic modalities to treat disease of the upper airway.(Ali and Pearson, 2007) Mucosal tissues represent the site of infection or the route of access for many bacteria and viruses that cause human disease. Mucins are a large glycosylated protein component of mucus. Mucin glycoproteins are produced by mucus-producing cells in the submucosal glands or the epithelium. They are responsible for the viscous properties of mucus.

The glycocalyx is formed underneath the mucus layer, it’s made up of highly diverse glycoproteins and glycolipids. A major constituent of the glycocalyx are the membrane-anchored cell-surface mucin glycoproteins. Mucins have a “bottle brush” appearance as each mucin forms a filamentous protein carrying 100s of complex oligosaccharide structures. The extended conformation caused by dense glycosylation allows the molecules to occupy large volumes. The expression of specific glycosyl transferases determine the carbohydrate structures present on mucins. Therefor mucin glycosylation is controlled by genetics, tissue specific enzyme expression, and host and environmental factors influencing transferase expression. Mucins are divided into three distinct subfamilies: cell surface mucins, secreted gel-forming mucins and secreted non-gel-forming mucins. Gel forming mucins are the major constituent of mucus and are responsible for its viscoelastic properties.(Linden et al., 2008)

Mucin glycoproteins play an important role in the innate immune system by providing a first line of defense against pathogens and by acting as a physical barrier against enzymatic, chemical and mechanical insult.(Pritchard et al., 2019) They have direct antimicrobial activity or carry other antimicrobial molecules. They also have the ability to opsonize microbes to aid clearance. (Linden et al., 2008) Although mucins are important in defense, mucin barriers can hinder drug delivery. The inhaled agents bind to the mucins and are removed by mucociliary clearance. Interfering with the muco-adhesive interactions, allowing agents to cross the mucin-protective layer of the lung, would significantly improve drug delivery.(Pritchard et al., 2019)

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Altered structure of mucins in CF

Mucins are important as they form the gel constituents in CF sputum. Modifications in mucins changes in the viscoelastic properties of mucus, as the addition of charged residues influences mucin aggregation. CF mucins have increased levels of galactose, fructose, N-acetylglucosamine, sulphate and sialic acid. The increases in glycosylation and branching of CF mucins have been shown to result in a higher tendency to gel and impede transport in vivo. Mucins in CF may also exhibit increased levels of sugar determinants during inflammation and infection (Pritchard et al., 2019)

Mucin glycosylation can alter in response to mucosal infection or inflammation, and this may be an important mechanism for unfavorably changing the niche occupied by mucosal pathogens (Linden et al., 2008)

The airway mucins in cystic fibrosis patients are over sulfated, this feature is a primary defect of the disease. The airway mucins in severely infected CF patients are also highly sialylated. They express sialylated and sulfated Lexis X determinants, which is a carbohydrate structure found on the non-reducing end of the mucin structure. This causes severe mucosal inflammation or infection. (Lamblin et al., 2001)

Figure 2(Burgel et al., 2007)

The figure shows the quantification of mucous glycoconjugates and mucins in the epithelium. The open symbols represent epithelium controls and the solid symbols represent patients with CF.

Pseudomonas Aeruginosa in Cystic fibrosis patients

One of the major causes of high morbidity and mortality in CF patients is pseudomonas aeruginosa. Pseudomonas aeruginosa is a gram-negative opportunistic pathogen, therefore it causes diseases when a person’s immune system is already impaired. For this reason, CF lungs are commonly infected by P. aeruginosa.

Pulmonary function starts to decline at an accelerated rate once infected with P. aeruginosa. “P. aeruginosa mucoid conversion within lungs of CF patients is a hallmark of chronic infection and predictive of poor prognosis”.(Malhotra et al., 2018)

Pseudomonas aeruginosa can be found widely in the environment. They are common pathogens involved in infections acquired in a hospital setting. When healthy people are infected with P. aeruginosa their infections are generally mild, however CF patients have weakened immune systems and will therefore suffer with more severe infections.

Once entering cystic fibrosis airways, P. aeruginosa is virtually impossible to eradicate due to its genome plasticity which allows it to adapt to the extremely stressful CF environment. Chronic infections can persist for years or decades. The challenging selective pressures caused by typical CF conditions such as low oxygen availability, interspecies competition, biofilm growth, the immune system, oxidative stress and antibiotic treatment drive P. aeruginosa. P. aeruginosa progressively generates phenotypes specifically adapted to CF airway conditions.(Sousa and Pereira, 2014) Because of this, early eradication of P. aeruginosa is very important as it avoids or at least retards the development of chronical infections and therefore preserving the lung function. However, some antibiotics fail to eradicate infection causing serious complications as the resistance subpopulations emerge. This is how chronic infections are established.(Sousa, Monteiro and Pereira, 2018)

Interaction between P. aeruginosa and CF mucins

An overabundance of mucus in CF airways provides a favourable niche for P. aeruginosa to grow. When comparing CF to non CF individuals the mucins recovered from CF airways are enriched in sialyl-Lewis x , this is a preferred binding receptor for P. aeruginosa. The levels of this sugar present directly correlate with the severity of infection in CF patients. Pulmonary infections caused by P. aeruginosa are a critical concern for CF patients, approximately 95% of patients are colonized with P. aeruginosa by the age of three. Pulmonary failure results in high morbidity and mortality in CF patients. Overproduction of hyper-viscous mucus and impeded mucociliary clearance of trapped microbes contribute to P. aeruginosa colonization in the CF airways. Mucin glycoproteins contain a diverse population of carbohydrate chains on their structure which have been shown to be receptors for bacteria. These mucin glycoproteins are a major component of airway mucus. Mucins in the airways have an intraluminal location, this is where microbes first interact in the lung. As previously mentioned CF mucins are enriched with the tetra-carbohydrate moiety sialyl-Lewis x. The enzymes that are crucial for the synthesis of this sugar, are upregulated during pulmonary inflammation. The levels of sialyl-Lewis x glycosylation on airway mucins directly correlate with the severity of the infection in CF patients. (Jeffries et al., 2016)

As well as binding to CF mucins, P. aeruginosa is also directly linked to mucus over production. P. aeruginosa lipopolysaccharide up regulates transcription of the mucin gene MUC 2 in epithelial cells. There is indication that the CFTR mutation is linked to three abnormalities which favour the onset and persistence of P. aeruginosa infection in the airways. The first abnormality is the undersialylated cell surface glycolipids that act as P. aeruginosa binding sites. The second abnormality is the decreased activity of bronchial bacteriolytic substances due to abnormal airway surfaces. The third is the impaired capacity for bronchial epithelial cells to clear P. aeruginosa by endocytosis. Overall the onset of P. aeruginosa in CF lungs causes lung deterioration. (Li et al., 1997)

There was a study carried out by (Flynn et al., 2016) to examine the possibility that mucins serve as an important carbon source for P. aeruginosa. The study concluded that P. aeruginosa was unable to efficiently utilize mucins in isolation, however they found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of P. aeruginosa, when provided intact mucins as a sole carbon source. Microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, this provides nutrients for pathogens that would otherwise be unable to obtain carbon from the lung.

  1. Ali, M. S. and Pearson, J. P. (2007) ‘Upper airway mucin gene expression: A review’, Laryngoscope, 117(5), pp. 932–938. doi: 10.1097/MLG.0b013e3180383651.
  2. Antoniou, S. (2016) ‘Cystic fibrosis Key points’, Medicine. Elsevier Ltd, 44(5), pp. 1–5. doi: 10.1016/j.mpmed.2016.02.016.
  3. Burgel, P. R. et al. (2007) ‘A morphometric study of mucins and small airway plugging in cystic fibrosis’, Thorax, 62(2), pp. 153–161. doi: 10.1136/thx.2006.062190.
  4. Davies, J. C., Alton, E. W. F. W. and Bush, A. (2007) ‘Cystic fibrosis’, British Medical Journal, 335(7632), pp. 1255–1259. doi: 10.1136/bmj.39391.713229.AD.
  5. Elborn, S. and Vallieres, E. (2014) ‘Cystic fibrosis gene mutations: evaluation and assessment of disease severity’, Advances in Genomics and Genetics, p. 161. doi: 10.2147/agg.s53768.
  6. Flynn, J. M. et al. (2016) ‘Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease’, PLoS Pathogens, 12(8), pp. 1–13. doi: 10.1371/journal.ppat.1005846.
  7. Jeffries, J. L. et al. (2016) ‘Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis x to increase binding to airway epithelial cells’, Mucosal Immunology, 9(4), pp. 1039–1050. doi: 10.1038/mi.2015.119.
  8. Lamblin, G. et al. (2001) ‘Human airway mucin glycosylation: A combinatory of carbohydrate determinants which vary in cystic fibrosis’, Glycoconjugate Journal, 18(9), pp. 661–684. doi: 10.1023/A:1020867221861.
  9. Li, J. D. et al. (1997) ‘Transcriptional activation of mucin by pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease’, Proceedings of the National Academy of Sciences of the United States of America, 94(3), pp. 967–972. doi: 10.1073/pnas.94.3.967.
  10. Lillehoj, E. (2017) Cellular and Molecular Biology of Airway Mucins, Physiology & behavior. doi: 10.1016/j.physbeh.2017.03.040.
  11. Linden, S. K. et al. (2008) ‘Mucins in the mucosal barrier to infection’, Mucosal Immunology, 1(3), pp. 183–197. doi: 10.1038/mi.2008.5.
  12. Lopes-Pacheco, M. (2016) ‘CFTR modulators: Shedding light on precision medicine for cystic fibrosis’, Frontiers in Pharmacology, 7(SEP), pp. 1–20. doi: 10.3389/fphar.2016.00275.
  13. Malhotra, S. et al. (2018) ‘Mixed communities of mucoid and nonmucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials’, mBio, 9(2), pp. 1–15. doi: 10.1128/mBio.00275-18.
  14. Meng, X. et al. (2017) ‘The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability’, Cellular and Molecular Life Sciences. Springer International Publishing, 74(1), pp. 23–38. doi: 10.1007/s00018-016-2386-8.
  15. Naehrig, S., Chao, C. M. and Naehrlich, L. (2017) ‘Cystic fibrosis - Diagnosis and treatment’, Deutsches Arzteblatt International, 114(33–34), pp. 564–573. doi: 10.3238/arztebl.2017.0564.
  16. Pritchard, M. F. et al. (2019) ‘Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum’, Vibrational Spectroscopy. Elsevier, 103(June), p. 102932. doi: 10.1016/j.vibspec.2019.102932.
  17. Sousa, A. M., Monteiro, R. and Pereira, M. O. (2018) ‘Unveiling the early events of Pseudomonas aeruginosa adaptation in cystic fibrosis airway environment using a long-term in vitro maintenance’, International Journal of Medical Microbiology. Elsevier, 308(8), pp. 1053–1064. doi: 10.1016/j.ijmm.2018.10.003.
  18. Sousa, A. M. and Pereira, M. O. (2014) ‘Pseudomonas Aeruginosa diversification during infection development in cystic fibrosis Lungs-A review’, Pathogens, 3(3), pp. 680–703. doi: 10.3390/pathogens3030680.
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