A specific secretion system mediates PPE41 transport in pathogenic mycobacteria.
Mycobacterial genomes contain two unique gene families, the so-called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT-6-like secretion system. This cluster, designated ESX-5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX-5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX-5 mutant of M. marinum was affected in spreading to uninfected macrophages.
Abdallah
Abdallah M
AM
Department of Medical Microbiology and Infection Control, VU Medical Centre, Amsterdam, the Netherlands.
Verboom
Theo
T
Hannes
Fredericke
F
Safi
Mohamad
M
Strong
Michael
M
Eisenberg
David
D
Musters
René J P
RJ
Vandenbroucke-Grauls
Christina M J E
CM
Appelmelk
Ben J
BJ
Luirink
Joen
J
Bitter
Wilbert
W
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D005810:Multigene Family; D009154:Mutation; D009161:Mycobacterium / Q000472:pathogenicity* / Q000502:physiology*; D021381:Protein Transport
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis