Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae.
Neisseria gonorrhoeae has evolved a complex and novel network of oxidative stress responses, including defence mechanisms that are dependent on manganese (Mn). We performed systematic analyses at the transcriptomic and proteomic (1D SDS-PAGE and Isotope-Coded Affinity Tag [ICAT]) levels to investigate the global expression changes that take place in a high Mn environment, which results in a Mn-dependent oxidative stress resistance phenotype. These studies revealed that there were proteins regulated at the post-transcriptional level under conditions of increased Mn concentration, including proteins involved in virulence (e.g., pilin, a key adhesin), oxidative stress defence (e.g., superoxide dismutase), cellular metabolism, protein synthesis, RNA processing and cell division. Mn regulation of inorganic pyrophosphatase (Ppa) indicated the potential involvement of phosphate metabolism in the Mn-dependent oxidative stress defence. A detailed analysis of the role of Ppa and polyphosphate kinase (Ppk) in the gonococcal oxidative stress response revealed that ppk and ppa mutant strains showed increased resistance to oxidative stress. Investigation of these mutants grown with high Mn suggests that phosphate and pyrophosphate are involved in Mn-dependent oxidative stress resistance.
Wu
Hsing-Ju
HJ
Core Facilities for Proteomics Research, Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan.
Seib
Kate L
KL
Srikhanta
Yogitha N
YN
Edwards
Jennifer
J
Kidd
Stephen P
SP
Maguire
Tina L
TL
Hamilton
Amanda
A
Pan
Kuan-Tin
KT
Hsiao
He-Hsuan
HH
Yao
Chen-Wen
CW
Grimmond
Sean M
SM
Apicella
Michael A
MA
McEwan
Alastair G
AG
Wang
Andrew H-J
AH
Jennings
Michael P
MP
D011756:Diphosphates; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D008345:Manganese / Q000494:pharmacology*; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010710:Phosphates; D040901:Proteomics; D037521:Virulence Factors / Q000235:genetics*
D011756:Diphosphates; D010710:Phosphates; D037521:Virulence Factors; D008345:Manganese