title: Deciphering the growth behaviour of Mycobacterium africanum.
abstract: BACKGROUND
  Human tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail.
  
  
  RESULTS
  We compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. We also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum.
  
  
  CONCLUSIONS
  The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells.
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium ; Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Florian
authors.initials: F
authors.lastname: Gehre
authors.forename: Jacob
authors.initials: J
authors.lastname: Otu
authors.forename: Kathryn
authors.initials: K
authors.lastname: DeRiemer
authors.forename: Paola Florez
authors.initials: PF
authors.lastname: de Sessions
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.forename: Wim
authors.initials: W
authors.lastname: Mulders
authors.forename: Tumani
authors.initials: T
authors.lastname: Corrah
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
mesh_terms: D003470:Culture Media / Q000737:chemistry; D005714:Gambia; D016680:Genome, Bacterial; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D006801:Humans; D009154:Mutation; D009161:Mycobacterium / Q000254:growth & development* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D026801:Synteny; D013997:Time Factors; D014376:Tuberculosis / Q000382:microbiology*; D037521:Virulence Factors / Q000235:genetics
chemical_list: D003470:Culture Media; D037521:Virulence Factors