Most protozoa are harmless, but some are pathogens that can cause disease in animals or humans Figure 5. Figure 5. Giardia lamblia , an intestinal protozoan parasite that infects humans and other mammals, causing severe diarrhea. Fungi singular: fungus are also eukaryotes.
Some multicellular fungi, such as mushrooms, resemble plants, but they are actually quite different. Fungi are not photosynthetic, and their cell walls are usually made out of chitin rather than cellulose. Figure 6. Candida albicans is a unicellular fungus, or yeast. It is the causative agent of vaginal yeast infections as well as oral thrush, a yeast infection of the mouth that commonly afflicts infants. Unicellular fungi—yeasts—are included within the study of microbiology.
There are more than known species. Yeasts are found in many different environments, from the deep sea to the human navel. Some yeasts have beneficial uses, such as causing bread to rise and beverages to ferment; but yeasts can also cause food to spoil. Some even cause diseases, such as vaginal yeast infections and oral thrush Figure 6. Other fungi of interest to microbiologists are multicellular organisms called molds. Molds are made up of long filaments that form visible colonies Figure 7.
Molds are found in many different environments, from soil to rotting food to dank bathroom corners. Molds play a critical role in the decomposition of dead plants and animals. Some molds can cause allergies, and others produce disease-causing metabolites called mycotoxins. Molds have been used to make pharmaceuticals, including penicillin, which is one of the most commonly prescribed antibiotics, and cyclosporine, used to prevent organ rejection following a transplant.
Figure 7. Large colonies of microscopic fungi can often be observed with the naked eye, as seen on the surface of these moldy oranges.
Multicellular parasitic worms called helminths are not technically microorganisms, as most are large enough to see without a microscope. However, these worms fall within the field of microbiology because diseases caused by helminths involve microscopic eggs and larvae. One example of a helminth is the guinea worm , or Dracunculus medinensis , which causes dizziness, vomiting, diarrhea, and painful ulcers on the legs and feet when the worm works its way out of the skin Figure 8. Infection typically occurs after a person drinks water containing water fleas infected by guinea-worm larvae.
In the mids, there were an estimated 3. In , there were only cases reported, thanks to the coordinated efforts of the World Health Organization WHO and other groups committed to improvements in drinking water sanitation. Figure 8. Viruses are acellular microorganisms, which means they are not composed of cells.
Essentially, a virus consists of proteins and genetic material—either DNA or RNA, but never both—that are inert outside of a host organism. Viruses can infect all types of cells, from human cells to the cells of other microorganisms. In humans, viruses are responsible for numerous diseases, from the common cold to deadly Ebola Figure 9. However, many viruses do not cause disease. Figure 9. Here they are viewed under a transmission electron microscope TEM.
Figure A virologist samples eggs from this nest to be tested for the influenza A virus, which causes avian flu in birds. Fish and Wildlife Service. Microbiology is a broad term that encompasses the study of all different types of microorganisms.
But in practice, microbiologists tend to specialize in one of several subfields. For example, bacteriology is the study of bacteria; mycology is the study of fungi; protozoology is the study of protozoa; parasitology is the study of helminths and other parasites; and virology is the study of viruses Figure Immunology , the study of the immune system, is often included in the study of microbiology because host—pathogen interactions are central to our understanding of infectious disease processes.
Microbiologists can also specialize in certain areas of microbiology, such as clinical microbiology, environmental microbiology, applied microbiology, or food microbiology. In this textbook, we are primarily concerned with clinical applications of microbiology, but since the various subfields of microbiology are highly interrelated, we will often discuss applications that are not strictly clinical.
In the s, the U. And then to make a multicellular organism, you need two kinds of interactions between cells. First, you need the ability to lay down an extracellular matrix, which bacteria are also perfectly capable of doing.
But then you need some kind of structural elements within cells that can connect to the extracellular matrix and to one another in such a way that forces can be continuously transmitted from the cells to the matrix and from one cell to another.
This is the property that is necessary for cells to make simple tissues such as epithelia, where sheets and ensembles of cells can get bigger and bigger and perform coherent behaviors.
In animal cells, these processes rely on the actin cytoskeleton [ 21 ], and there is evidence that similar cytoskeleton-based processes are also necessary for simpler kinds of multicellularity in non-metazoan eukaryotes such as Dictyostelium [ 22 ] and Volvox [ 23 ]. The problem with this argument about the basis of the difference between eukaryotes and bacteria is that it all depends on bacteria not having a cytoskeleton, which is what we believed in the early s.
But then it was discovered by several very convincing converging lines of evidence, spearheaded by Joe Lutkenhaus, that the bacterial protein FtsZ, which forms a ring around the middle of the bacterial cell and has an essential role in cell division [ 24 ], is a homolog of tubulin [ 25 , 26 ]. And when the atomic structures for both tubulin and FtsZ were solved at the same time, it was absolutely clear that they were nearly superimposable and almost certainly true homologs in the sense of being derived from a common ancestor [ 27 , 28 ].
So there went the assumption that bacteria do not have a cytoskeleton. But then a few years later, in a series of quite spectacular papers where the cell biological evidence for the shape-determining role of a certain class of bacterial actin-like proteins including MreB [ 29 ], was staggeringly confirmed by the undeniable structural similarity between MreB and actin [ 30 ], it was quite clearly demonstrated that bacteria do in fact have actin homologs.
In the 10 years or so since that discovery, a lot of people have been searching for more different examples of actin and tubulin homologs in bacteria, and indeed we can find a tremendous number of such homologs, a vast proliferation with different biological functions, with various actin homologs like ParM involved in plasmid segregation [ 31 ] and MamK necessary for magnetosome alignment [ 5 ].
And in a few bacteria, there is even some evidence that they have homologs or at least functional analogs of intermediate filament proteins [ 34 ]. So we must absolutely acknowledge that the major eukaryotic cytoskeletal proteins are also present in our bacterial comrades, indeed there are many copies of them with distinct biological functions.
So I would like to rephrase the question about what the difference is between eukaryotes and bacteria. We now know that everyone has a cytoskeleton, but still there are fundamental and easily observable morphological differences between these two domains of life, where eukaryotes have used their cytoskeletons to get larger and more morphologically complex and even truly multicellular, while bacteria basically have not done so. At least, I have a hypothesis. I think it is at least a unifying concept that I hope will be provocative, and perhaps lead to experiments and analysis that might really test this idea.
The starting point for my hypothesis is that the central feature of the cytoskeletal elements that are universally shared among organisms, and are necessary for cellular life, is the ability to form protein polymers that can give rise to large-scale cell organization and cell division via the dynamic assembly and disassembly of helical protein filaments.
That is found everywhere. Besides the actin- and tubulin-related cytoskeletal proteins in bacteria, there are structures like bacterial flagella and bacterial pili, which are also fundamentally helical homopolymers of proteins. Bacteria are perfectly good at making those kinds of structures. They are perfectly good at governing the dynamics of those structures. Here is my hypothesis: eukaryotes enhance the intrinsic assembly features of the helical filament protein systems with two particular kinds of cytoskeleton-associated factors, which have not yet been found in bacteria.
And those two are regulated nucleators - centrioles for example - and linear stepping molecular motor proteins - the eukaryotic myosin and kinesin molecules. There are other actin nucleators and there are other microtubule nucleators that operate by different mechanisms. But it seems from those two examples that a very reasonable way to regulate the initiation and assembly of helical cytoskeletal polymers is to just make another copy of the gene for the subunit and then allow it to specialize a little bit so that it becomes a regulatable nucleator.
Certainly that is the sort of thing that bacteria could do if they wanted. They would have no problem duplicating and modifying the genes for the cytoskeletal proteins, as they have demonstrated with the proliferation of the different flavors of actin and tubulin homologs that are used in such a wide variety of contexts. For example, Bacillus subtilis has three different chromosomally encoded paralogs, each of which is homologous to actin, MreB, Mbl, and MreBH, that appear to have somewhat overlapping functions [ 40 ].
But so far, we do not know of any specialized actin- or tubulin-related proteins in bacteria that are used specifically as regulated nucleators for their main self-assembling subunits MreB and FtsZ.
Cytoskeletal filament nucleation by modified subunits. Left: diagram of microtubule templated from a ring complex Copyright from Molecular Biology of the Cell, 5th edition by Alberts et al. Right, electron micrograph of the end of a microtubule nucleated from a ring complex reprinted by permission from Macmillan Publishers Ltd: Nat Cell Biol 2: — , copyright [ 42 ].
This is the corollary to my argument. If my hypothesis that bacteria do not have regulated cytoskeletal nucleation proteins is true - and I will go through the cell biological evidence that makes me think this is true - then the question is whether they really do not want to have them or whether they just never had the opportunity to develop them.
I think, at least as far as nucleators go, the opportunity to develop them is not a very high barrier. So I think it must be that bacteria simply have a fundamentally different strategy for cytoplasmic organization as compared to eukaryotes. However, at least in the case of actin, there are many different, distinct molecular families of nucleators that can operate by different but equally simple mechanisms.
For example, the actin nucleators Spire [ 45 ] and Cordon-bleu [ 46 ] both appear to nucleate actin by having a series of three or four domains that bind directly or indirectly to actin monomers; these domains can bring the actin subunits into close enough proximity and appropriate enough orientation to get over the kinetic barrier to actin nucleation and start the growth of a filament.
In the particular case of this category of nucleators, I am quite confident that bacteria would be able to develop them if they wanted to, as indeed two bacterial pathogens are known to express secreted virulence factors that act as host cell actin nucleating factors by exactly this mechanism [ 47 , 48 ]. For these virulence factors, it is not clear whether the pathogens picked up their actin nucleators by horizontal gene transfer or by convergent evolution, but in either case it is still striking that bacteria are easily able to nucleate eukaryotic actin filaments but do not seem to have any regulated protein nucleators for their own cytoskeletal filaments.
But the thing that I think is really interesting about cytoskeletal filament nucleation in this context is that classically when we were taught the theory of protein polymerization from Fumio Oosawa [ 49 , 50 ] and Terrell Hill [ 51 , 52 ] and all those giants in the field, their argument was that it is important, kinetically, that nucleation be the rate-limiting step for polymer formation.
And that is indeed observably true for actin and for microtubules and for the bacterial flagellum, the classical examples of helical protein self-assembly that they were trying to describe with their comprehensive theoretical treatments. But when people started doing very careful kinetic studies on the bacterial cytoskeletal proteins - and this I think has been done best for FtsZ [ 53 ] and for ParM [ 54 ] - it became clear that nucleation for the bacterial cytoskeletal proteins is actually very, very fast.
The way bacterial cells regulate where they have their filaments is not by regulating the site of nucleation, but rather by regulating the sites of stabilization and destabilization of spontaneously nucleating filaments.
For those of us who have been raised on the thermodynamic theory of protein polymerization in the context of cell biology, this is deeply shocking. Spatial localization of cytoskeletal components in bacteria simply appears to use a fundamentally different mode of organization from the one we see for all of the organized cytoskeletal assemblies in eukaryotes, and frankly we as cell biologists are justified in being a little bit freaked out.
The dynamic cytoskeletal polymers found in bacteria seem to be just as important to the bacterial cells as they are to us eukaryotes, and they are involved in similarly crucial cell biological processes. Also the bacterial cytoskeletal proteins are very widely distributed among bacteria and even archaea [ 55 , 56 ]. I absolutely do not mean to disparage the many very interesting things that bacteria do and have done in their evolutionary history.
The cyanobacteria invented oxygenic photosynthesis for which I am very grateful, and in general bacteria have much more interesting twists on metabolism than do us chemically unimaginative eukaryotes. But I do realistically claim organismal size, morphological complexity, and true multicellularity as eukaryote-specific features that deserve explaining.
As we delve into the details of my argument I will delineate a few of the many biological examples of well-understood systems that have convinced me that bacteria simply do not have cytoskeletal nucleators or cytoskeletal motor proteins as we understand them in eukaryotes. The diagram in Figure 2 shows - given some reasonable assumptions about the universality and fundamental nature of helical protein filament assembly - what larger-scale structures you can get with and without nucleators and motors.
In particular these drawings show structures that can be formed by polarized cytoskeletal filaments, where the subunits assemble in a head-to-tail fashion so that the two ends of the filaments are structurally distinct. According to the basic theories of protein polymerization, this is expected to give a polymer where the kinetics of subunit addition and loss at the two ends are also distinct, where one end grows and shrinks more quickly than the other [ 51 ]. In microtubules, the fast-growing end is called the plus end and the slow-growing end is called the minus end.
In actin filaments, the fast-growing end is called the barbed end and the slow-growing end is called the pointed end. Types of cytoskeletal filament arrays. Type A : simple filament arrays that can self-assemble in the absence of spatially regulated nucleators or molecular motor protiens.
Shading indicates the orientation of filament polarity. Type B : complex filament arrays that require either nucleation or motor protein activity, or both. Dark circles represent nucleators. The simple structures that can be made from polarized filaments I will call type A structures. In the absence of nucleators you can obviously make a single filament of essentially any length and that single filament can have many protofilaments.
A microtubule is a single filament with 13 protofilaments that can be arbitrarily long. A bacterial flagellum is also a single filament that happens to have 11 protofilaments, and flagella can also be very long - 10 microns long in vivo.
Both of these structures self-assemble quite nicely from solutions of purified protein monomers; indeed these were the examples that have formed much of the basis of our understanding of the fundamental thermodynamics of protein polymerization [ 50 ].
So those kinds of structures you can make regardless of whether you are a bacterium or a eukaryote and regardless of the presence of nucleators or motors.
The other kind of structure that is very easy to make is a mixed polarity bundle. In crowded solutions, such as in the cytoplasm of a living cell, colloidal rods will tend to align with one another simply because of entropy and excluded volume effects [ 57 ]. When the rods happen to be cytoskeletal filaments, they can easily form bundles either by interacting with one another laterally, or else by having cross-linking proteins that help pull them together.
For the bacterial cytoskeleton, the clearest example of a mixed polarity bundle is the plasmid-segregating actin homolog ParM, which can assemble into mixed polarity bundles on its own [ 58 ]. It is also very likely that the FtsZ ring in bacterial cytokinesis is essentially a mixed polarity bundle, formed with the help of cross-linking proteins [ 59 ]. The kinds of structures for which I think, theoretically, you need to have either localized nucleation or motor activity, or both, the type B structures, are structures like asters, where many cytoskeletal filaments with the same polarity emanate from a single location, or parallel bundles of filaments, where all of the filaments are pointing in the same direction.
If filaments form spontaneously and then come together through purely entropic effects, there is no intrinsic reason for them to assemble in a particular orientation. So if you want to have a parallel bundle, such as in a muscle sarcomere, you have to control the assembly or orientation of the filaments, for example by having them all nucleated from the same site.
And of course a great example of all of these properties is the mitotic spindle, where you have parallel bundling and anti-parallel bundling of microtubules, and also their nucleation from particular sites at the spindle poles.
There are plenty of examples of single polarized filaments in bacteria. There are plenty of examples of mixed polarity filament bundles in bacteria. But the type B structures are critical I think to making eukaryotes what we are today, by allowing the elaboration of the microtubule cytoskeleton to give complex organelle dynamics and fabulously flexible DNA segregation capacity, and elaboration of the actin cytoskeleton to give us the possibility of amoeboid motion and phagocytosis, which allow us to run around and eat all those pesky bacterial biofilms and tame endosymbionts.
And then once we have those kinds of structures and mechanisms, we are able to overcome the diffusion barrier and the increase in size and complexity of eukaryotic cells follows naturally from that.
The supporting details can be discussed from three different perspectives. The first focuses on self-assembly dynamics, and the rules about the kinetics and thermodynamics of self-assembly that come from the intrinsic properties of proteins - can these really be different between bacteria and eukaryotes? And if not, why not? And beyond that, there are also other possible explanations besides the cytoskeletal hypothesis for why eukaryotes and bacteria are different; this is a fourth level, even more general and more speculative, but one that I think helps tie this whole story together.
The first thing to think about is the question of protein self-assembly, because classically, when we think about the cytoskeleton, we imagine lots of little subunits that are able to assemble in an oriented fashion, to make larger structures. The ability of proteins to form homo-oligomers is very prevalent and, in fact, I would say it is almost the default thing for proteins to be able to do.
Structural biologists have done a very nice job of breaking down the kinds of symmetries you can get in these homo-oligomers into different kinds of classifications. Really making a helix is just one particular phylogenetic group, if you will, of the kinds of structures that proteins can make by self-assembly.
Now there are two really nice things about helices. One is that a helix enables you to make structures of variable length, while most other oligomer types make a closed structure with a defined size, such as a viral capsid. But a helix that grows by addition of subunits onto the end can in principle be tuned over a very wide size or length range. They used protein structural arguments to explain that when you allow many copies of the same protein to aggregate together you can hardly help but make a helix Figure 3 a.
If you allow a protein to self-assemble, a helix of some kind is going to be the default. Helical protein filaments formed by self-assembly. For any globular protein of arbitrary shape, as shown at the top, considered as interacting with a second copy of itself in all possible orientations, there will be some pair of surface patches that result in optimal binding energy.
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Liz Sockett explores some current equal opportunity issues which affect everyone training and working in microbiology. Transmission from badgers was blamed for these and a controversial government-funded culling trial began. The BSE crisis of the late 80s and early 90s led to cutbacks in proven measures of controlling bovine TB and the recent foot-and-mouth outbreak led to the suspension of testing.
TB in cattle is now rising and spreading rapidly. Martin Hancox asks, are badgers really to blame? Eukaryotic microbes 01 August publication The lead articles of the August issue of Microbiology Today are on eukaryotic microbes; fungal pathogens; DNA damage responses; the evolution of photosynthetic eukaryotes; new hope for the neglected diseases; how do fungi choose what to eat?
Eukaryotic microbes: something for everyone p. Fungal pathogens - the devil is in the detail p.
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