1 Siderophores: Biochemical Ecology and Mechanism of Iron Transport in Enterobacteria
J. B. NEILANDS Downloaded by 111.178.18.102 on April 9, 2016 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/ba-1977-0162.ch001
Department of Biochemistry, University of California, Berkeley, CA 94720
Siderophores protect Escherichia coli and Salmonella typhi murium from certain phages, bacteriocins, and antibiotics by two mechanisms. Thefirstis adsorption competition for outer membrane receptors. Thus ferrichrome competes with T1, T5, Φ80, colicin M, and albomycin for a common site (tonA) in Escherichia coli and with phage ES18 and albomycin in Salmonella. Ferric enterobactin similarly antagonizes colicin B. In the second mechanism sidero phores nonspecifically protect against the Β group colicins in an event requiring use of siderophore iron. Ferric entero bactin and cognate membrane receptors are overproduced at low levels of iron. Experiments with Fe and tritiated ligand and with the isostructural chromic analog show that ferrichrome rapidly delivers its iron while the ligand more slowly, although again as the iron complex, penetrates the cell. 55
T T n t i l recently the problem of iron assimilation in microbial species ^ could be likened to a quiet, pastoral scene with a few "low powered" microbiologists and biochemists patiently tending their crop. Just in the past two years, however, this scene has been changed radically by the sudden shift of emphasis from structural chemistry and fungi to mem brane physiology and enteric bacteria. Things happen fast in enteric bacteria, and we conclude that progress is directly proportional to the generation time of the species. It was the finding of a common locus for attachment of microbial iron transport compounds (siderophores), phages, and colicins at the outer membrane of Escherichia coli,firstre3 Raymond; Bioinorganic Chemistry—II Advances in Chemistry; American Chemical Society: Washington, DC, 1977.
4
BIOINORGANIC CHEMISTRY
II
p o r t e d i n 1974 (1), t h a t c h a n g e d t h e t e m p o f r o m subsistence f a r m i n g to agribusiness. A c c o r d i n g l y , this c h a p t e r deals m a i n l y w i t h s o m e o f t h e v e r y r e c e n t a d v a n c e s i n k n o w l e d g e of i r o n t r a n s p o r t systems i n e n t e r i c b a c t e r i a .
I
review critically a n d place i n historic perspective current understanding of t h e c o m p e t i t i o n p h e n o m e n o n
between phages, colicins, a n d sidero-
phores f o r outer m e m b r a n e receptors, t h e resistance to c e r t a i n c o l i c i n s i m p a r t e d b y i r o n , a n d , finally, t h e m e c h a n i s m of s i d e r o p h o r e - m e d i a t e d iron uptake. T h e g e n e r a l p r o p e r t i e s of s i d e r o p h o r e s h a v e b e e n d e s c r i b e d e x t e n s i v e l y (2), a n d u p - t o - d a t e lists of the i n d i v i d u a l c o m p o u n d s , t h e i r sources Downloaded by 111.178.18.102 on April 9, 2016 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/ba-1977-0162.ch001
f r o m a e r o b i c a n d f a c u l t a t i v e a e r o b i c species, a n d t h e i r p r o p e r t i e s h a v e b e e n p u b l i s h e d (3,4,5).
( P o r p h y r i n Products, P . O . B o x 31, L o g a n , U T
84321, sell a l i m i t e d n u m b e r of siderophores. ) T h e e a r l i e r l i t e r a t u r e o n i r o n a s s i m i l a t i o n b y m i c r o b e s , i n c l u d i n g e n t e r i c species, m a y b e f o u n d elsewhere
(6,7).
F o r information o n the chemical constitution a n d
p h y s i o l o g i c a l r o l e of t h e outer m e m b r a n e of e n t e r i c b a c t e r i a , t h e r e a d e r is r e f e r r e d t o N a k a e a n d N i k a i d o
Roles of Iron in Microbial
(8).
Physiology and Processes for Its
Assimilation
It is w e l l to r e c a l l that t h e t h e o r e t i c a l basis f o r this r e s e a r c h resides i n t h e o m n i p r e s e n t r o l e of i r o n i n m i c r o b i a l p h y s i o l o g y ( 9 ) . I r o n c o m p o u n d s , f r o m t h e f e r r e d o x i n s to c y t o c h r o m e
oxidase, transfer electrons
over a r e d o x p o t e n t i a l s p a n n i n g t h e b e t t e r p a r t of o n e v o l t . T h e f e r r e doxins thus s u p p l y t h e l o w p o t e n t i a l electrons r e q u i r e d f o r r e d u c t i o n of nitrogen a n d carbon dioxide i n nitrogen
fixation
a n d photosynthesis,
respectively, w h i l e the cytochromes enable respiration a n d concomitant c o n s e r v a t i o n of c h e m i c a l energy.
T h e significance of i r o n storage a n d
o x y g e n t r a n s p o r t p r o t e i n s i n m i c r o b e s is l a r g e l y u n k n o w n , a l t h o u g h o n e m o l d species i n yeast.
contains f e r r i t i n , a n d h e m o g l o b i n - l i k e c o m p o u n d s
occur
T h e i r o n - c o n t a i n i n g oxygenases a n d h y d r o p e r o x i d a s e s
play
essential roles i n o x y g e n a n d h y d r o g e n p e r o x i d e m e t a b o l i s m . O n e f o r m of s u p e r o x i d e d i s m u t a s e contains i r o n (10).
T h e b i o l o g i c a l r e d u c t i o n of
nitrogen requires, i n addition to ferredoxin, a n iron protein a n d a n i r o n m o l y b d e n u m p r o t e i n . F i n a l l y , i n E. coli a n d i n a l l other m i c r o b e s n o t utilizing the functionally equivalent vitamin B p o n e n t of r i b o t i d e reductase.
i
2
s y s t e m , i r o n is a c o m -
T h u s i r o n has a k e y r o l e i n t h e synthesis
of t h e D N A of m i c r o o r g a n i s m s , i n c l u d i n g t h e e n t e r i c species. I n v i e w of t h e m a n y c r u c i a l b i o f u n c t i o n s of i r o n , i t m i g h t b e exp e c t e d that m i c r o b e s w o u l d b e e q u i p p e d w i t h d i v e r s e systems f o r a c q u i r i n g t h e m e t a l . T h e s e c a n b e d e s i g n a t e d l o w affinity ( n o n s p e c i f i c ) h i g h affinity ( s p e c i f i c ) .
or
T h e f o r m e r c a n b e b l o c k e d b y use of a c h e l a t o r
Raymond; Bioinorganic Chemistry—II Advances in Chemistry; American Chemical Society: Washington, DC, 1977.
1.
5
Iron Transport in Enterobacteria
NEILANDS
t h a t is n o t a s s i m i l a t e d , e.g., c i t r a t e i n the case o f Salmonella
typhimurium.
T h e h i g h affinity system i n v o l v e s specific c a r r i e r m o l e c u l e s ( s i d e r o p h o r e s ) a n d a cognate m e m b r a n e r e c e p t o r transport system. T h e t w o c o m p o n e n t s of t h e h i g h affinity system
can b e altered b y mutation, a n d they
h e n c e accessible t o the e x p e r i m e n t a l
methods of biochemical
are
genetics.
T h i s c h a p t e r w i l l b e r e s t r i c t e d t o the h i g h affinity system, t h e m a i n c o n tours o f w h i c h are d e p i c t e d i n F i g u r e 1.
