title: Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.
abstract: BACKGROUND
  Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discovery of new drug targets.
  
  
  RESULTS
  We conducted an in silico analysis of 19 mycobacterial species/clinical strains for the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L-alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing for classification of mycobacterial species into three main categories, primarily based on their rpf gene complement. These include the M. tuberculosis Complex (MTBC), other pathogenic mycobacteria and environmental species. The complement of these genes within the MTBC and other mycobacterial pathogens is highly conserved. In contrast, environmental strains display significant genetic expansion in most of these gene families. Mycobacterium leprae retains more than one functional gene from each enzyme family, underscoring the importance of genetic multiplicity for PG remodelling. Notably, the highest degree of conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that these enzymes are essential for growth and survival.
  
  
  CONCLUSIONS
  PG remodelling enzymes in a range of mycobacterial species are associated with extensive genetic multiplicity, suggesting functional diversification within these families of enzymes to allow organisms to adapt.
authors.forename: Edith Erika
authors.initials: EE
authors.lastname: Machowski
authors.forename: Sibusiso
authors.initials: S
authors.lastname: Senzani
authors.forename: Christopher
authors.initials: C
authors.lastname: Ealand
authors.affiliation: DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, P,O, Box 1038, Johannesburg 2000, South Africa. bavesh.kana@nhls.ac.za.
authors.forename: Bavesh Davandra
authors.initials: BD
authors.lastname: Kana
mesh_terms: D019295:Computational Biology; D017124:Conserved Sequence; D004783:Environmental Microbiology; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D009161:Mycobacterium / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D009164:Mycobacterium Infections / Q000382:microbiology; D010457:Peptidoglycan / Q000378:metabolism*
chemical_list: D010457:Peptidoglycan