By Nitara Wijayatilake
Pseudomonas aeruginosa is an opportunistic pathogen, taking advantage of existing infections to cause extreme detriment to immune-suppressed individuals. With respect to its classification, it is a gram-negative alpha-proteobacteria and 10% of its genome is made up of regulatory genes, influencing its highly adaptable nature. This bacteria has a wide host range but research has focused on one of its most fatal effects: in the lungs of cystic fibrosis patients (Williams, 2021).
Pseudomonas aeruginosa is extremely effective in producing infection due to its ability to produce hydrogen cyanide. This works by a method of quorum sensing, where bacteria are able to detect their population size and if the population density is high, act on it. The synthesis of hydrogen cyanide requires a low environmental oxygen concentration and a high population density. If these conditions are met, P. aeruginosa can undergo oxidative decarboxylation of a glycine to hydrogen cyanide, catalysed by the enzyme hydrogen cyanide synthase. It is well-known that Cyanide is toxic – it can irreversibly bind terminal oxidases, preventing cellular respiration thus, killing cells. The question arises: does P. aeruginosa die from the cyanide? In fact, no. The bacteria are able to avoid the toxic chemical by possessing a terminal oxidase in their respiratory chain, which is insensitive to hydrogen cyanide. This survival mechanism provides P. aeruginosa with a significant advantage in the different niches it occupies, increasing its pathogenicity majorly (Lenney & Gilchirst, 2011).
Further to that, the condition cystic fibrosis is caused by mutations in the gene encoding for CFTR (cystic fibrosis transmembrane conductance regulator protein), which is a chloride ion channel. In patients with this mutation, the regulations of salt and fluids is affected and therefore, the hydration of mucosal secretions is decreased (YourGenome, 2016). Cystic fibrosis patients can easily accumulate thick mucus in the lung and be exposed to chronic lung infections, by bacteria such as Pseudomonas aeruginosa. Importantly, this mucus provides a steep oxygen concentration gradient due to the overconsumption of oxygen at the epithelial cell level. This means P. aeruginosa moves into an environment, deep in the lungs, which is in low oxygen or anaerobic conditions (Williams, Zlosnik & Ryall, 2006).
As previously mentioned, this bacteria is highly adaptable and has specific respiratory adaptability to allow it to combat low oxygen conditions by switching its terminal oxidase in the respiratory chain. In low oxygen, it may use Cytochrome cbb3 as a terminal oxidase which has a higher affinity to oxygen to help with its adaptation. Alternatively, nitrate oxidase may be used in anaerobic pathways. The differential expression of multiple terminal oxidases demonstrates the highly adaptable nature of P. aeruginosa. It is thought that here, in the cystic fibrosis lung, hydrogen cyanide can be synthesised and inhibit respiration, causing severe pathogenetic effects and destroying lung function (Williams, Zlosnik & Ryall, 2006). There have been associations made on lung function, in particular the ciliary beat of lungs cells and the presence of cyanide. There have also been links between the presence of Pseudomonas aeruginosa and the synthesis of hydrogen cyanide, confirmed by the absence of any other microorganism (Nair et al, 2014).
Moreover, the infection of Pseudomonas aeruginosa is chronic and is generally considered a leading cause of mortality in cystic fibrosis patients. Interestingly, this bacteria is often resistant to antibiotics and can maintain a chronic infection in its desired environment for an extended period of time. This is most probably due to an accumulation of mutations, facilitated by the formation of a biofilm. As a consequence of interspecies communication, such as quorum sensing, bacteria are often able to form an organised community within a biofilm which acts as a barrier, allowing a resistance to toxic compounds such as antibiotics. (Donlan, 2001). In the cystic fibrosis lung, it is likely that biofilms form in anaerobic conditions so to allow persistent and chronic infection (Murray et al, 2007).
Fortunately, macrolide drugs are often effective in preventing the formation of biofilms in the lungs and therapies are being developed to disrupt quorum sensing in the cystic fibrosis lung (Murray et al, 2007). One of the problems faced is administering drugs to both the sputum and respiratory zones of the lung as both can be infected by Pseudomonas aeruginosa. Another issue is the burden faced by cystic fibrosis patients who experience an extensive number of practice treatments, which continued adherence to may be challenging (Hoiby, 2011). Nevertheless, the devastating effects of this highly adaptable and poisonous bacteria must be tackled till a successful therapy is found.
Huw Williams. 2021. Respiratory adaptability in Pseudomas aeruginosa. [Lecture] Molecular Microbiology. Imperial College London. 28.01.2021
Lenney, W. and Gilchrist, F., 2011. Pseudomonas aeruginosa and cyanide production. European Respiratory Journal, 37(3), pp.482-483.
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Williams, H., Zlosnik, J. and Ryall, B., 2006. Oxygen, Cyanide and Energy Generation in the Cystic Fibrosis Pathogen Pseudomonas aeruginosa. Advances in Microbial Physiology, pp.1-71.
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Murray, T., Egan, M. and Kazmierczak, B., 2007. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Current Opinion in Pediatrics, 19(1), pp.83-88.
Høiby, N., 2011. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. BMC Medicine, 9(1).