Lung Infections C 3 Pseudomonas Aeruginosa and Other Related Species

Thorax 1998;53:213–219 213 Lung infections c 3 Thorax: first published as 10.1136/thx.53.3.213 on 1 March 1998. Downloaded from Series editor: S L Hill Pseudomonas aeruginosa and other related species Robert Wilson, Ruth B Dowling Pseudomonas aeruginosa was first obtained in (Burkholderia) cepacia is a distant relation of P pure culture by Gessard in 1882 from cutan- aeruginosa and was first described as a cause of eous wounds which had a blue green soft rot in onions. It is ubiquitous in the discolouration1 and is the major human patho- environment and is frequently found in associ- gen from a large genus of strictly aerobic ation with soil, water and plants. Like P aerugi- Gram-negative rods which are widely distrib- nosa, it is virtually non-pathogenic in healthy uted in nature.2 The majority of P aeruginosa people, but it can cause disease in those with strains produce at least two pigments, a reduced host defences, and it has been fluorescent yellow pigment and a blue pigment recognised as an important pathogen in cystic called pyocyanin, which together give the char- fibrosis.8 P cepacia may be isolated alone or acteristic colour noted above when the bacte- together with P aeruginosa. This may lead to rium is grown on agar.3 P aeruginosa is motile problems in isolating P cepacia because P aeru- by means of a single flagellum and thrives in ginosa rapidly outgrows it on agar unless selec- 8 moist environments; it is extremely versatile tive media are used. P pseudomallei is widely biochemically and can grow in many habitats distributed in the soil and water of rice paddy including soil, surface waters, plants and fields and causes melioidosis, which is a major various foods such as vegetables eaten by cause of death from community acquired sep- man.24In hospitals P aeruginosa can be found ticaemia in Thailand and is endemic through- 9 in sinks, respirators, humidifiers, etc, and is out south east Asia and northern Australia. occasionally found on the hands of medical http://thorax.bmj.com/ 2 personnel. Epidemiology P aeruginosa is an opportunistic pathogen Although the initial isolation of P aeruginosa which only causes disease in patients with from sputum may be intermittent in cystic impaired host defences. The patient’s defences fibrosis and other forms of bronchiectasis, once may be generally weakened by debility or can- chronic infection is established it is rarely pos- cer, or there may be specific humeral or cellu- sible to eradicate it even with intensive lar defects. Neutropenic patients are especially antibiotic therapy.561011A number of longitu- susceptible to pseudomonas infection and to dinal bacteriological studies of cystic fibrosis on September 24, 2021 by guest. Protected copyright. subsequent septicaemia. Alternatively, the patients have shown that most of them harbour body’s defences may be specifically breached as the same P aeruginosa clone for many years.12–14 in corneal ulceration or skin burns, or artifi- Once a particular clone has colonised the lung cially overcome as with assisted ventilation or DNA fingerprinting may reveal shifts in the by an indwelling urinary catheter.4 Patients macrorestriction fragment patterns, indicating with bronchiectasis are particularly prone to subclonal variation, which may result from chronic infection, and delayed mucociliary sequence alterations in restriction recognition clearance may be responsible.56 The use of sites, genomic rearrangements, and incorpora- broad spectrum antibiotics may kill commensal tion of extrachromosomal DNA—for example, flora or more antibiotic-sensitive pathogenic from bacteriophages.15 Available evidence sug- species causing infection, and promote coloni- gests that acquisition of P aeruginosa is sation by the intrinsically resistant commonly from the environment, but that pseudomonas.7 P aeruginosa is particularly patient to patient spread can occur particularly associated with progressive and ultimately fatal if contact density is high such as can occur at chronic respiratory infection in cystic fibrosis. cystic fibrosis centres and recreation camps.15–17 Host Defence Unit, Clues about the biological basis of this P cepacia can cause respiratory tract infection Imperial College of host-bacterial interaction which occurs almost in cystic fibrosis,818 although it is much less Science, Technology and Medicine, inevitably are just being discovered. In this common in non-cystic fibrosis bronchiectasis. National Heart and review we will only cover chronic airway infec- Strains are usually very antibiotic resistant and Lung Institute, London tions, although some of the information is rel- have in some studies been associated with rapid SW3 6LR, UK evant to acute pneumonia and septicaemia clinical deterioration,1819 although this is not R Wilson which are most commonly seen in immuno- always the case.19 20 Anxiety has also been R B Dowling compromised patients. increased by reports of cross-infection between 21–23 Correspondence to: Two other pseudomonas species which cause patients although not all studies have found Dr R Wilson. disease in humans will be mentioned briefly. P evidence of this.24 Nevertheless, some centres 214 Wilson, Dowling Table 1 Virulence factors of Pseudomonas aeruginosa Virulence factor Biological action Thorax: first published as 10.1136/thx.53.3.213 on 1 March 1998. Downloaded from Mucoid exopolysaccharide (alginate) Adherence to epithelium; barrier to phagocytes and antibiotics; inhibits antibody and complement binding Protease enzymes Tissue damage; epithelial cell tight junction separation; degrade fibronectin; cleave antibodies creating non-functional blocking antibodies; inactivate á1-antiproteinase, complement components and cytokines; cleave C3b receptors from neutrophils; stimulate mucus secretion Exotoxin A Cytotoxic by inhibiting protein synthesis; toxic to macrophages; T cell mitogen; inhibits granulocyte and macrophage progenitor cell proliferation Lipopolysaccharide Dominant antigenic determinant on cell surface; loss of sugar unit side chains during chronic infection creates “rough” LPS and serum sensitivity; less potent endotoxin properties than other Gram-negative species Pigments eg. pyocyanin, 1-hydroxyphenazine, Inhibit ciliary beat; siderophores; toxic to other bacterial species and human pyoverdin cells; enhance oxidative metabolism of neutrophils; inhibit lymphocyte proliferation Phospholipase C Haemolysis; tissue damage; destroy surfactant Rhamnolipid Haemolysis; inhibit ciliary beat; stimulate mucus secretion, aVect ion transport across epithelium Pili Adherence to epithelium Lipase Tissue damage Histamine Impair epithelial integrity Exoenzyme S Adherence to epithelium; cytotoxic Leukocidin Cytotoxic to neutrophils and lymphocytes Compiled from references 2, 3, 10, 11, 25, 26, 31–35, 41, 42, 49, 64, 68, 78, 81, 82. have segregated patients carrying P cepacia. surface occurred when there was cell damage The benefits of such a policy need to be clearly or exposure of underlying connective tissue.27 defined because of the psychosocial implica- The importance of epithelial damage (fig 1) in tions of segregation and further epidemiologi- facilitating P aeruginosa adherence has been cal data are urgently needed.820 noted in numerous studies, and the bacterium does not seem to adhere to normal Bacterial pathogenesis epithelium.28 Cell damage might remove de- P aeruginosa does not cause infection in the fence mechanisms such as ciliary beating which absence of impaired host defences, yet a wide would otherwise protect the epithelium,3 and array of potential virulence factors have been also expose new receptors for bacterial adhes- described which may contribute to its patho- ins on damaged cells, on newly exposed genicity in the compromised patient. A review surfaces, and on cells that grow to repair the of the literature is summarised in table 1. The damage.28–30 Pili have been identified as an failure of the bacterium to infect the healthy important adhesin of P aeruginosa31 32 but do lung—or even the mildly compromised de- not account for all the adhesive properties and http://thorax.bmj.com/ fences of, say, a patient with chronic other adhesins such as a protein linked with bronchitis—means that no single virulence flagellar biosynthesis,33 exoenzyme S,34 and factor is by itself that potent, but that the whole alginate35 have been identified. array should be viewed as contributing to the P aeruginosa has a high aYnity for human “pathogenic personality” of the bacterium. tracheobronchial mucus in vitro, mucus of Once colonisation of the airways is established, organ cultures (fig 1) and in the airways.27 28 36 P aeruginosa is rarely eliminated despite an Bacterial adherence to mucus probably in- 625 exuberant host inflammatory response. volves both specific and non-specific on September 24, 2021 by guest. Protected copyright. The mucoid form of P aeruginosa produces interactions.37–40 P aeruginosa proteases and large amounts of an extracellular polysaccha- rhamnolipid also stimulate mucus ride called alginate, and this form accounts for production.41 42 In organ cultures P aeruginosa up to 90% of isolates from patients with cystic grows as continuous sheets over the mucus fibrosis.226Typically, the first time that P aeru- surface28 and it has been shown that growth in ginosa is isolated it is non-mucoid but after a such biofilms is resistant to opsonophagocytic variable period, often one or two years, it killing by neutrophils.43 44 P aeruginosa adher- becomes mucoid. Although patients infected ence to mucus, and its lack

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