Deciphering the genetic basis for polyketide variation among mycobacteria producing mycolactones

Pidot, Sacha J.; Hui Hong; Seemann, Torsten; Porter, Jessica L.; Yip, Marcus J.; Men, Artem; Johnson, Matthew; Wilson, Peter; Davies, John K.; Leadlay, Peter F.; Stinear, Timothy P.
January 2008
BMC Genomics;2008, Vol. 9, Special section p1
Academic Journal
Background: Mycolactones are immunosuppressive and cytotoxic polyketides, comprising five naturally occurring structural variants (named A/B, C, D, E and F), produced by different species of very closely related mycobacteria including the human pathogen, Mycobacterium ulcerans. In M. ulcerans strain Agy99, mycolactone A/B is produced by three highly homologous type I polyketide megasynthases (PKS), whose genes (mlsA1: 51 kb, mlsA2: 7.2 kb and mlsB: 42 kb) are found on a 174 kb plasmid, known as pMUM001. Results: We report here comparative genomic analysis of pMUM001, the complete DNA sequence of a 190 kb megaplasmid (pMUM002) from Mycobacterium liflandii 128FXT and partial sequence of two additional pMUM replicons, combined with liquid chromatography-tandem mass spectrometric (LC-MS/ MS) analysis. These data reveal how PKS module and domain differences affecting MlsB correlate with the production of mycolactones E and F. For mycolactone E these differences from MlsB in M. ulcerans Agy99 include replacement of the AT domain of the loading module (acetate to propionate) and the absence of an entire extension module. For mycolactone F there is also a reduction of one extension module but also a swap of ketoreductase domains that explains the characteristic stereochemistry of the two terminal side-chain hydroxyls, an arrangement unique to mycolactone F Conclusion: The mycolactone PKS locus on pMUM002 revealed the same large, three-gene structure and extraordinary pattern of near-identical PKS domain sequence repetition as observed in pMUM001 with greater than 98.5% nucleotide identity among domains of the same function. Intra- and inter-strain comparisons suggest that the extreme sequence homogeneity seen among the mls PKS genes is caused by frequent recombination-mediated domain replacement. This work has shed light on the evolution of mycolactone biosynthesis among an unusual group of mycobacteria and highlights the potential of the mls locus to become a toolbox for combinatorial PKS biochemistry.


Related Articles

  • Distribution of Nontuberculous Mycobacteria strains. Gunaydin, Murat; Yanik, Keramettin; Eroglu, Cafer; Sanic, Ahmet; Ceyhan, Ismail; Erturan, Zayre; Durmaz, Riza // Annals of Clinical Microbiology & Antimicrobials;2013, Vol. 12 Issue 1, p1 

    Aim Mycobacteria other than tuberculosis (MOTT) cause increasingly serious infections especially in immunosuppressive patients by direct transmission from the environment or after colonization. However, identification of these species is difficult because of the cost and difficulties in defining...

  • Three cases of atypical mycobacterial cervical adenitis. Montague, Mary-Louise; Musheer Hussain, S. S.; Blair, Robin L. // Journal of the Royal Society of Medicine;Mar2003, Vol. 96 Issue 3, p129 

    The article presents three case histories of atypical mycobacterial cervical adenitis. Such infections are acquired from environmental sources which are contaminated as suggested by epidemiological evidence. Distinguishing between adenitis caused by atypical myobacteria and M. tuberculosis poses...

  • Use of 16S rDNA Sequences as Signature Characters to Identify Xylella fastidiosa. Chen, Jianchi; Banks, Donna; Jarret, Robert L.; Chang, Chung J.; Smith, Barbara J. // Current Microbiology;Jan2000, Vol. 40 Issue 1, p29 

    The nucleotide sequences of 16S rDNAs (coding for the small subunit ribosomal RNAs) were used to identify Xylella fastidiosa, a nutritionally fastidious plant pathogenic bacterium. The near-complete 16S rDNAs from nine strains of Xyl. fastidiosa, including seven pathotypes and one strain of...

  • Dependence of linkage of alleles on their physical distance in natural transformation of Acinetobacter sp. strain ADP1. Gerischer, Ulrike; Ornston, L. Nicholas // Archives of Microbiology;Dec2001, Vol. 176 Issue 6, p465 

    The interdependence of genetic linkage in transformation and physical distance was studied in the bacterium Acinetobacter sp. strain ADP1. Transformation experiments were performed using 17 strains containing different mutations within the 21-kb pca-qui-pob gene cluster as recipients for the DNA...

  • Analyses of bifidobacterial prophage-like sequences. Ventura, Marco; Turroni, Francesca; Foroni, Elena; Duranti, Sabrina; Giubellini, Vanessa; Bottacini, Francesca; van Sinderen, Douwe // Antonie van Leeuwenhoek;Jun2010, Vol. 98 Issue 1, p39 

    The genomes of 22 putative prophages (bifidoprophages), previously identified in bifidobacterial genomes, were analyzed to detect the presence and organization of functional modules. Bifidoprophages were shown to display a classical modular genomic organization in which the DNA lysogeny module...

  • The Use of a Combination of alkB Primers to Better Characterize the Distribution of Alkane-Degrading Bacteria. Jurelevicius, Diogo; Alvarez, Vanessa Marques; Peixoto, Raquel; Rosado, Alexandre S.; Seldin, Lucy // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    The alkane monooxygenase AlkB, which is encoded by the alkB gene, is a key enzyme involved in bacterial alkane degradation. To study the alkB gene within bacterial communities, researchers need to be aware of the variations in alkB nucleotide sequences; a failure to consider the sequence...

  • Mycobacterium marinum infections in humans and tracing of its possible environmental sources. Slany, Michal; Jezek, Petr; Fiserova, Vera; Bodnarova, Monika; Stork, Jiri; Havelkova, Marta; Kalat, Frantisek; Pavlik, Ivo // Canadian Journal of Microbiology;Jan2012, Vol. 58 Issue 1, p39 

    The low frequency of nontuberculous mycobacterial infections, nonspecific symptoms for individual mycobacteria, and the lack of specific identification methods could alter correct diagnosis. This study presents a combined microbiology and molecular-based approach for Mycobacterium marinum...

  • Culturable actinobacteria isolated from marine sponge Iotrochota sp. Shumei Jiang; Xiang Li; Long Zhang; Wei Sun; Shikun Dai; Lianwu Xie; Yonghong Liu; Kyung Lee // Marine Biology;Mar2008, Vol. 153 Issue 5, p945 

    The study describes the diversity of actinobacteria isolated from the marine sponge Iotrochota sp. collected in the South China Sea. Species and natural product diversity of isolates were analyzed, including screening for genes encoding polyketide synthases (PKS) and nonribosomal peptide...

  • Characterization of Rhizobium grahamii extrachromosomal replicons and their transfer among rhizobia. Althabegoiti, Maria Julia; Ormeño-Orrillo, Ernesto; Lozano, Luis; Tejerizo, Gonzalo Torres; Rogel, Marco Antonio; Mora, Jaime; Martínez-Romero, Esperanza // BMC Microbiology;2014, Vol. 14 Issue 1, p1 

    Background Rhizobium grahamii belongs to a new phylogenetic group of rhizobia together with Rhizobium mesoamericanum and other species. R. grahamii has a broad-host-range that includes Leucaena leucocephala and Phaseolus vulgaris, although it is a poor competitor for P. vulgaris nodulation in...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics