Chemistry Reference
In-Depth Information
cytoplasm of these bacteria they must cross two membranes and the periplasmic space. As we will see in what
follows, this requires quite a number of transport proteins. In contrast, Gram-positive bacteria have a very thick
cell wall confronting the external environment, and their unique outer membrane plays a role which is similar to
that of the plasma membrane in Gram-negative bacteria.
While we tend to talk about transition metals as trace elements, in terms of their actual concentration within indi-
vidual bacterial cells, they are found at concentrations which are several orders of magnitude higher than the concen-
tration in a typical bacterial growth medium. Thus, in Escherichia coli, Fe and Zn are present at around 2
10
5
atoms/
cell, which corresponds to around 0.1 mM, while intracellular Cu, Mn, Mo, and Se levels are around 10
M.
The impact of genome-sequencing projects on our understanding about metal-assimilation pathways has been
enormous, particularly among organisms with genomes that are not too large, nor too complex. The first complete
genomes to be sequenced were those of small RNA and DNA viruses. Today, the complete genome sequence of
over 1500 bacteria have been determined, and for the family of Cyanobacteria, the complete genomic sequence of
around 40 members of the family are known. This of course means that once a metal assimilation gene has been
identified, its presence and presumed functionality can be assigned to other family members. In a similar manner,
identification of a gene with homology to a known transport protein in any other bacterial species can lead to the
putative identification of the corresponding pathway in other bacteria. Clearly, there is one small codicil
m
the
e
presence of the gene does not establish that it is expressed
that requires the much more exacting task of showing
e
that the gene product (i.e., the protein) is indeed present.
In what follows, we discuss uptake, i.e., assimilation of metal ions from the environment into the organism
itself. Later, in Chapter 8, we consider metal transport, storage, and homeostasis within organisms and cells.
1.
Iron
Because of both the low solubility of ferric iron (at pH 7 the free Fe
3
þ
concentration is around 10
9
M) and the
large amounts of iron required for their growth, bacteria have developed a large variety of iron uptake systems.
These probably reflect the type of iron sources present in their particular environment at a given time. Most of the
abundant nutrients required for Gram-negative bacteria diffuse across the outer membrane passively through
transmembrane channels made up of porins, to pass into the periplasm. However, scarce metals like iron and
cobalt (e.g., vitamin B12 in the GI tract of humans in the case of the common colon bacteria E. coli) need to be
transported actively across each layer of the cell envelope.
5
In the case of iron, as we briefly described in
Chapter 4, this is achieved by synthesising and secreting into their surrounding environment highly specific Fe
3
þ
-
complexing compounds, termed siderophores, which are taken up by specific transport systems. They may also
use ambient iron sources, such as Fe
3
þ
-loaded siderophores from other bacteria and fungi. E. coli produces
endogenously only one siderophore, enterobactin, the biosynthesis of which we described in Chapter 4. However,
it has outer-membrane receptors for the uptake of a number of exogenous ferric hydroxamate siderophores, like
ferrichrome and ferrioxamine, which it is itself incapable of synthesising, as well as the periplasmic transporter
FhuB and the inner membrane ABC transporter FhuCD, necessary for their uptake.
6
It also has an uptake system
which enables it to acquire iron from ferric citrate, despite the fact that ferric citrate is neither a carbon nor an
energy source for E. coli, as well as a specific uptake system for Fe
2
þ
, which allows it to grow anaerobically.
Many highly pathogenic bacteria can also acquire iron from the haem of their mammalian hosts, by secreting
proteins called haemophores which release haem from haemoglobin to specific transport proteins in the outer
membrane. Yet other pathogens can use iron bound to transferrin and to lactoferrin. The list of pathogenic microor-
ganisms which are able to use the mammalian host's iron transport systems reads like a roll call fromHell's kitchen of
human bacterial diseases
e
Haemophilus influenzae (awide range of clinical diseases, but, surprisingly not influenza!),
Neisseria meningitidis (meningitis), Neisseria gonorrhoeae (gonorrhea), Pseudomonas aeruginosa (an opportunistic
5. If a bacterial cell waited for simple diffusion of 10
9
MFe
3
þ
through porins, it would die instantaneously!
6. The yeast Saccharomyces cerevisiae goes one better
e
it itself synthesises no siderophores, but has no less than four plasma membrane
facilitators for uptake and internalization of several ferric siderophores.
