Limits...
Mycobacterium tuberculosis proteins involved in mycolic acid synthesis and transport localize dynamically to the old growing pole and septum.

Carel C, Nukdee K, Cantaloube S, Bonne M, Diagne CT, Laval F, Daffé M, Zerbib D - PLoS ONE (2014)

Bottom Line: The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci.Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope.As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.

ABSTRACT
Understanding the mechanism that controls space-time coordination of elongation and division of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is critical for fighting the tubercle bacillus. Most of the numerous enzymes involved in the synthesis of Mycolic acid - Arabinogalactan-Peptidoglycan complex (MAPc) in the cell wall are essential in vivo. Using a dynamic approach, we localized Mtb enzymes belonging to the fatty acid synthase-II (FAS-II) complexes and involved in mycolic acid (MA) biosynthesis in a mycobacterial model of Mtb: M. smegmatis. Results also showed that the MA transporter MmpL3 was present in the mycobacterial envelope and was specifically and dynamically accumulated at the poles and septa during bacterial growth. This localization was due to its C-terminal domain. Moreover, the FAS-II enzymes were co-localized at the poles and septum with Wag31, the protein responsible for the polar localization of mycobacterial peptidoglycan biosynthesis. The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci. This finding highlights a major difference between mycobacteria and other rod-shaped bacteria studied to date. Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope. As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages.

Show MeSH

Related in: MedlinePlus

Schematic representation of mycobacterial polar growth and establishment of bacterial poles.Two division cycles (D1 and D2) are presented. The active biosynthesis of lateral peptidoglycan at the poles and biosynthesis of septal peptidoglycan at the future pole (septal poles) are symbolized with curved arrows. The old pole (in red) and the new pole (in blue); are both represented and refer to the first division event (D1).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4016276&req=5

pone-0097148-g001: Schematic representation of mycobacterial polar growth and establishment of bacterial poles.Two division cycles (D1 and D2) are presented. The active biosynthesis of lateral peptidoglycan at the poles and biosynthesis of septal peptidoglycan at the future pole (septal poles) are symbolized with curved arrows. The old pole (in red) and the new pole (in blue); are both represented and refer to the first division event (D1).

Mentions: The cell wall elongation process of actinobacteria[4] is different from that of other rod-shaped models such as Escherichia coli or Bacillus subtilis[22]. In the latters, nascent PG is made all along the side of the bacterium during elongation and at the septum during the division process [23] whereas in the former, the lateral PG derives from polar biosynthesis during elongation [24]. Among mycobacteria, the polar localization of PG synthesis is mainly due to the phospholipid-interacting protein Wag31, the ortholog of the B. subtilis DivIVA protein [25], [26], [27]. Wag31, by targeting negatively-curved membranes [28], is responsible for the polar localization and the septal re-localization of several PG biosynthesis proteins [29], [30]. Wag31 is mainly located at the “old pole” (Figure 1), which is the active locus among mycobacteria and other actinobacteria where new molecular material of the lateral cell wall is added [31], [32]. The “septal pole” (Figure 1), which represents the future pole and the developing septum, does not participate in lateral PG biosynthesis [33].


Mycobacterium tuberculosis proteins involved in mycolic acid synthesis and transport localize dynamically to the old growing pole and septum.

Carel C, Nukdee K, Cantaloube S, Bonne M, Diagne CT, Laval F, Daffé M, Zerbib D - PLoS ONE (2014)

Schematic representation of mycobacterial polar growth and establishment of bacterial poles.Two division cycles (D1 and D2) are presented. The active biosynthesis of lateral peptidoglycan at the poles and biosynthesis of septal peptidoglycan at the future pole (septal poles) are symbolized with curved arrows. The old pole (in red) and the new pole (in blue); are both represented and refer to the first division event (D1).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016276&req=5

pone-0097148-g001: Schematic representation of mycobacterial polar growth and establishment of bacterial poles.Two division cycles (D1 and D2) are presented. The active biosynthesis of lateral peptidoglycan at the poles and biosynthesis of septal peptidoglycan at the future pole (septal poles) are symbolized with curved arrows. The old pole (in red) and the new pole (in blue); are both represented and refer to the first division event (D1).
Mentions: The cell wall elongation process of actinobacteria[4] is different from that of other rod-shaped models such as Escherichia coli or Bacillus subtilis[22]. In the latters, nascent PG is made all along the side of the bacterium during elongation and at the septum during the division process [23] whereas in the former, the lateral PG derives from polar biosynthesis during elongation [24]. Among mycobacteria, the polar localization of PG synthesis is mainly due to the phospholipid-interacting protein Wag31, the ortholog of the B. subtilis DivIVA protein [25], [26], [27]. Wag31, by targeting negatively-curved membranes [28], is responsible for the polar localization and the septal re-localization of several PG biosynthesis proteins [29], [30]. Wag31 is mainly located at the “old pole” (Figure 1), which is the active locus among mycobacteria and other actinobacteria where new molecular material of the lateral cell wall is added [31], [32]. The “septal pole” (Figure 1), which represents the future pole and the developing septum, does not participate in lateral PG biosynthesis [33].

Bottom Line: The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci.Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope.As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages.

View Article: PubMed Central - PubMed

Affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.

ABSTRACT
Understanding the mechanism that controls space-time coordination of elongation and division of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is critical for fighting the tubercle bacillus. Most of the numerous enzymes involved in the synthesis of Mycolic acid - Arabinogalactan-Peptidoglycan complex (MAPc) in the cell wall are essential in vivo. Using a dynamic approach, we localized Mtb enzymes belonging to the fatty acid synthase-II (FAS-II) complexes and involved in mycolic acid (MA) biosynthesis in a mycobacterial model of Mtb: M. smegmatis. Results also showed that the MA transporter MmpL3 was present in the mycobacterial envelope and was specifically and dynamically accumulated at the poles and septa during bacterial growth. This localization was due to its C-terminal domain. Moreover, the FAS-II enzymes were co-localized at the poles and septum with Wag31, the protein responsible for the polar localization of mycobacterial peptidoglycan biosynthesis. The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci. This finding highlights a major difference between mycobacteria and other rod-shaped bacteria studied to date. Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope. As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages.

Show MeSH
Related in: MedlinePlus