Structure of a peptidoglycan amidase effector targeted to Gram-negative bacteria by the type VI secretion system.
The target range of a bacterial secretion system can be defined by effector substrate specificity or by the efficacy of effector delivery. Here, we report the crystal structure of Tse1, a type VI secretion (T6S) bacteriolytic amidase effector from Pseudomonas aeruginosa. Consistent with its role as a toxin, Tse1 has a more accessible active site than related housekeeping enzymes. The activity of Tse1 against isolated peptidoglycan shows its capacity to act broadly against Gram-negative bacteria and even certain Gram-positive species. Studies with intact cells indicate that Gram-positive bacteria can remain vulnerable to Tse1 despite cell wall modifications. However, interbacterial competition studies demonstrate that Tse1-dependent lysis is restricted to Gram-negative targets. We propose that the previously observed specificity for T6S against Gram-negative bacteria is a consequence of high local effector concentration achieved by T6S-dependent targeting to its site of action rather than inherent effector substrate specificity.
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Seemay
S
Chou
Nhat Khai
NK
Bui
Alistair B
AB
Russell
Katrina W
KW
Lexa
Taylor E
TE
Gardiner
Michele
M
LeRoux
Waldemar
W
Vollmer
Joseph D
JD
Mougous
D000581:Amidohydrolases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D058947:Bacterial Secretion Systems; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D004187:Disaccharides; D010457:Peptidoglycan; D000581:Amidohydrolases; C019665:amidase