Understanding Pseudomonas Aeruginosa in Cystic Fibrosis Patients

The pathogen targeting the vulnerable

Cystic Fibrosis (CF) is a detrimental genetic disease, with one in 3500 babies being born with CF in the United States (WHO 2019). The side effects limit daily life dramatically, and there is currently no cure. However, the leading causes of death aren’t due to the disease itself, but due to the microbiota that thrive within the environment of a CF patient. Among this biota is Pseudo Aeruginosa, a harmful pathogen which drastically increases the morbidity and mortality of CF patients. Once infected in the patient, it becomes virtually impossible to eradicate. What makes this pathogen so harmful, and why only to CF patients?

What is Cystic Fibrosis?

Cystic Fibrosis (CF) is a genetic disease which primarily occurs within the Caucasian population; however, there are diagnoses within other racial and ethnic groups (Bhagirath et al. 2016). CF is the cause of a genetic mutation of the CFTR gene. The primary role of the CFTR gene is to regulate and move ions throughout the body. A non-functioning CFTR gene has numerous effects on multiple organs within the body. The most notable is the build-up of thick and sticky mucus in organs including the lungs. This thick mucus sets up the perfect environment for microbiota to thrive, both good and bad. One of the bad ones is Pseudomonas Aeruginosa.

Image 1: Bacteria visual (Source: Cystic Fibrosis News Today)

Pseudomonas Aeruginosa

Pseudomonas Aeruginosa (P.Aeruginosa) is a gram-negative, rod-shaped bacterium. The bacterium exists in many natural environments; however, its primary habitat is known to be water. P.Aeruginosa is a highly versatile organism with many metabolic pathways. This comes down to its unusually large genome that allows the bacterium to live off little nutrients and in both anaerobic and aerobic conditions also making it the perfect pathogen for patients suffering with CF.

In the late 1950s, the occurrence of P.Aeruginosa within CF patients started to become something of interest. It was discovered that up to 70-87% of CF patients had colonies of the pathogen present in their respiratory tract in comparison to only 0.8-2.1% of patients from the general population (Fick 1992). Colonisation of P.Aeruginosa in CF patients causes a significant decline in respiratory function, leading to higher morbidity and mortality. (Pritt, O’Brien & Winn 2007). A study in 2002 revealed that the 8-year risk of death was 2.6 times higher for CF patients with P.Aeruginosa than those without it. (Emerson et al. 2002). Making this pathogen extremely fearful for patients with Cystic Fibrosis and understanding of how it works, extremely necessary.

Why Cystic Fibrosis patients?

Unfortunately, the exact mechanisms P.Aeruginosa uses to cause respiratory failure is not entirely understood; however what is known is how it thrives. 

The immune system of CF patients is usually weaker than the system of a non-CF person. The epithelial cells (cells that line the surfaces of your body) of someone without CF can consume and destroy invading pathogens such as P.Aeruginosa and therefore protect the respiratory tract. However, in a CF patient, their epithelial cells are unable to kill as many cells of P.Aeruginosa. (Bhagirath et al 2016) The conditions of the CF respiratory tract are unfortunately suitable for the colonisation of the pathogen as they also protect the species from dehydration and research has found that the airway acidification due to CFTR malfunction further disrupts the host defence mechanisms. (Pritt, O’Brien & Winn 2007; Bhagirath et al 2016).

A Change in Phenotype

Initial colonisation often occurs at a young age; however, by the age of 20, 80% of CF patients are termed ‘chronically infected’ by the pathogen. The term ‘chronic’ is associated with the intriguing mutation of the pathogen into a mucoid strain. (Bhagirath et al 2016; Emerson J et al 2002). This mucoid strain is distinguished by the secretion of a large amount of extracellular polymeric substances (polymers that are high in molecular weight and excreted by microorganisms) called alginate. The alginate forms a matrix which assists in the creation of a biofilm. (Pritt, O’Brien & Winn 2007; Owlia et al. 2014). In the lab, this mucoid strain of the pathogen can be identified by its discrete gram stain. As seen in Figure 1, large amounts of orange alginate material surround each gram-negative rod.

As mentioned, the mucoid form leads to the formation of a biofilm. This biofilm acts as a protective mechanism for the pathogen. However, this makes it more dangerous for CF patients as studies reveal that biofilm formation is the main cause of lung infections.

Figure 1: Gram stain of mucoid P.Aeruginosa. (Source Pritt, B., O’Brien, L., Winn, W. 2007)

Once formed, the pathogen is protected from opsonisation (cells ability to target the pathogen), phagocytosis (engulfing of the pathogen) and resistance from antibiotics. (Pritt, O’Brien & Winn 2007). Essentially making the pathogen indestructible. On top of this, research has found that lung conditions will further shift to favour the survival of the pathogen (Bhagirath et al 2016).

What are the treatments?

Treatments of the P.Aeruginosa are usually ineffective because once in the mucoid state, it becomes virtually impossible to eradicate the pathogen. At best, antibiotic regimes can reduce their cell density. Because of this, treatments are aimed at either preventing early infection or preventing from the pathogen mutating into a mucoid state. (Fick 1992; Horsely, Cunningham & Innes 2015; Pritt, O’Brien & Winn 2007)

References

• Bhagirath, A.Y., Li, Y., Somayajula, D., Dadashi, M., Badr, S. Duan, K. 2016, ‘Cystic fibrosis lung environment and Pseudomonas aeruginosa infection’, BMC Pulmonary Medicine, vol. 16, no. 1, p. 174.
• Emerson, J., Rosenfeld, M., McNamara, S., Ramsey, B., Gibson, RL. 2002, ‘Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis’, Pediatric Pulmonology, vol. 34, no. 2, p. 91-100.
• Fick, R.B. 1992, Pseudomonas Aeruginosa: The opportunist, CRC Press, Iowa
• Horsley, A., Cunningham, S. Innes, A.J. 2015, Cystic Fibrosis, 2, Oxford University Press
• Owlia, P., Nosrati, R., Alaghebandan, R., Lari, A.R. 2014, ‘Antimicrobial susceptibility differences among mucoid and non-mucoid Pseudomonas aeruginosa isolates’, GMS Hygience and Infection Control, vol.9, no.2, Doc. 13.
• Pritt, B., O’Brien, L., Winn, W. 2007, ‘Mucoid Pseudomonas in Cystic Fibrosis’, Microbiology and Infectious Disease
• World Health Organization 2004, Genes and Human Diseases, viewed 4 May 2019, https://www.who.int/genomics/public/geneticdiseases/en/index2.html

Images

• Cystic Fibrosis News Today 2019, Link Found Between P. Aeruginosa infection and Disease Severity in CF Patients, Study Reports, viewed May 6^th 2019, https://cysticfibrosisnewstoday.com/2019/01/30/link-pseudomonas-aerguinosa-infection-disease-severity/