Desulfurization of mucin by Pseudomonas aeruginosa: influence of sulfate in the lungs of cystic fibrosis patients.
Pseudomonas aeruginosa is a common cause of chronic respiratory infection in cystic fibrosis (CF) patients. Infection is established within the lung epithelial mucus layer through adhesion to mucins. Terminal residues on mucin oligosaccharide chains are highly sulfated and sialylated, which increases their resistance to degradation by bacterial enzymes. However, a number of microbes, including P. aeruginosa, display mucin sulfatase activity. Using ion chromatography, the levels of sulfation on different respiratory mucins and the availability of inorganic sulfate to pathogens in sputum from CF patients were quantified. The ability of clinical isolates of P. aeruginosa to desulfate mucin was tested by providing mucin as a sole sulfur source for growth. All tested P. aeruginosa strains isolated from the lungs of CF patients were able to use human respiratory mucin as a source of sulfur for growth, whereas other non-clinical species of the genus Pseudomonas were not. However, measured levels of inorganic sulfate in sputum from CF patients suggested that bacteria resident in the lung have sufficient inorganic sulfate for growth and are unlikely to require access to mucin sulfur as a sulfur source during chronic infection. This was confirmed when expression of sulfate-repressed P. aeruginosa genes atsK and msuE was found to be repressed in the sputum of CF patients, which was detected by using quantitative RT-PCR. These results indicate that sulfate starvation is unlikely to occur in pathogens residing in the sputum of CF patients and, therefore, mucin desulfation may have an alternative purpose in the association between P. aeruginosa and the airways of CF patients.
Faculty of Life Sciences, University of Manchester, Oxford Rd, Manchester M13 9PT, UK.
Camilla V
CV
Robinson
Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
Mark R
MR
Elkins
Faculty of Agriculture and Environment, University of Sydney, Sydney, NSW 2006, Australia.
Katarzyna M
KM
Bialkowski
Faculty of Life Sciences, University of Manchester, Oxford Rd, Manchester M13 9PT, UK.
David J
DJ
Thornton
Faculty of Agriculture and Environment, University of Sydney, Sydney, NSW 2006, Australia.|Faculty of Life Sciences, University of Manchester, Oxford Rd, Manchester M13 9PT, UK.
Michael A
MA
Kertesz
D000328:Adult; D001422:Bacterial Adhesion; D003550:Cystic Fibrosis / Q000382:microbiology*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D009077:Mucins / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000382:microbiology; D013183:Sputum / Q000737:chemistry / Q000382:microbiology; D013429:Sulfatases / Q000378:metabolism; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*
D009077:Mucins; D013431:Sulfates; D013429:Sulfatases; C074449:mucin sulfatase