MutS deficiency and activity of the error-prone DNA polymerase IV are crucial for determining mucA as the main target for mucoid conversion in Pseudomonas aeruginosa.
Pseudomonas aeruginosa colonizes the respiratory tract of cystic fibrosis (CF) patients, where mutators along with mucoid variants emerge leading to chronic infection. Mucoid conversion generally involves mutations inactivating the mucA gene. This study correlates the frequency and nature of mucA mutations with the activity of factors determining the mutation rate, such as MutS and polymerase IV (Pol IV). Results show that: (i) the emergence frequency of mucoid variants was higher in isolates arising from mutS populations compared with the wild-type strain; (ii) in both strains mucoid conversion occurred mainly by mucA mutations; (iii) however, the mutator strain harboured mostly mucA22 (a common allele in CF isolates), while the wild type showed a wider spectrum of mucA mutations with low incidence of mucA22; (iv) disruption of dinB in the wild-type and mutS strains decreased drastically the emergence frequency of mucoid variants; (v) furthermore, the incidence of mucA mutations diminished in the mutS dinB double mutant strain which consisted only in mucA22; (vi) finally, the mucoid isolates obtained from the dinB strain showed an unexpected absence of mucA mutations. Taken together results demonstrate the implication of both MutS and Pol IV in determining mucA as the main target for conversion to mucoidy.
Moyano
Alejandro J
AJ
Centro de Investigaciones en Química Biológica de Córdoba, CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.
Luján
Adela M
AM
Argaraña
Carlos E
CE
Smania
Andrea M
AM
D001426:Bacterial Proteins / Q000378:metabolism*; D019951:DNA Polymerase beta / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D051719:MutS DNA Mismatch-Binding Protein / Q000172:deficiency* / Q000378:metabolism*; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000302:isolation & purification
D001426:Bacterial Proteins; D006025:Glycosaminoglycans; C107895:MucA protein, Pseudomonas; C046129:mucoid exopolysaccharide (P aeruginosa); D019951:DNA Polymerase beta; D051719:MutS DNA Mismatch-Binding Protein