Single amino acid substitution in homogentisate 1,2‐dioxygenase is responsible for pigmentation in a subset of Burkholderia cepacia complex isolates

Abstract

Summary The Burkholderia cepacia complex (Bcc) is a group of Gram-negative bacilli that are ubiquitous in the environment and have emerged over the past 30 years as opportunistic pathogens in immunocompromised populations, specifically individuals with cystic fibrosis (CF) and chronic granulomatous disease. This complex of at least 18 distinct species is phenotypically and genetically diverse. One phenotype observed in a subset of Burkholderia cenocepacia (a prominent Bcc pathogen) isolates is the ability to produce a melanin-like pigment. Melanins have antioxidant properties and have been shown to act as virulence factors allowing pathogens to resist killing by the host immune system. The melanin-like pigment expressed by B. cenocepacia is produced through tyrosine catabolism, specifically through the autoxidation and polymerization of homogentisate. Burkholderia cenocepacia J2315 is a CF clinical isolate that displays a pigmented phenotype when grown under normal laboratory conditions. We examined the amino acid sequences of critical enzymes in the melanin synthesis pathway in pigmented and non-pigmented Bcc isolates, and found that an amino acid substitution of glycine for arginine at amino acid 378 in homogentisate 1,2-dioxygenase correlated with pigment production; we identify this as one mechanism for expression of pigment in Bcc isolates.

Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection

“…S3 in the supplemental material). Pyomelanin pigment, detected by absorbance at 480 nm ( 44 ), was significantly inhibited by CYS at concentrations above 8 μg/ml. The inhibition of these virulence determinants at sub-MICs may have further benefit therapeutically to enhance cotherapies and assist the innate and adaptive immune responses to infection.…”

Comparative Genomics of Environmental and Clinical Burkholderia cenocepacia Strains Closely Related to the Highly Transmissible Epidemic ET12 Lineage

“…B. cenocepacia , especially strains from the ET12 lineage, are among the most prevalent Bcc members that colonize CF patients ( Isles et al, 1984 ; Speert et al, 2002 ; Mahenthiralingam et al, 2005 ; Drevinek and Mahenthiralingam, 2010 ). However, despite that many virulence factors were described, the epidemiological success of some lineages is still misunderstood ( Holden et al, 2009 ; McClean and Callaghan, 2009 ; Bazzini et al, 2011a ; Gonyar et al, 2015 ). The B. cenocepacia species is characterized by a large variety of ecological niches, from patient-associated to environmental niches.…”

Disruption of hmgA by DNA Duplication is Responsible for Hyperpigmentation in a Vibrio anguillarum Strain

“…cholerae 38 , A . salmonicida 37 , Legionella pneumophila 31 , Shewanella colwelliana 32 , Burkholderia cepacia 35 , B . cenocepacia 36 , Streptomyces avermitilis 34 , Ralstonia solanacearum 30 .…”

“…A search for this characteristic, i.e., higher pigmentation, in other bacteria showed that a subset of Burkholderia cepacia strains includes a deficient hmgA gene. In this case, rather than the truncation, the variant of the hmgA gene codes for a protein that has an amino acid substitution that is detrimental for enzymatic activity 35 .…”