How can microorganisms damage the body

Learn More. Many infections are associated with damage inflicted either directly or indirectly by invading pathogens. Although some infections do not result in host damage, it is often a natural consequence of the activities of virulence factors produced by the pathogens in order to facilitate survival, and proliferation in the host or onward transmission to another host.

The damage often manifests itself as the symptoms of disease which can be useful for diagnosis and for informing appropriate treatments. A wide array of different types of toxins which cause damage to the host are produced by different bacterial pathogens.

Here we provide examples of well-characterised toxins and describe their mechanisms of action, and potential function with regard to pathogenesis. In addition we describe indirect damage to the host in the form of inflammation or immunopathology, typically the result of the host's own immune response.

Finally, we discuss diarrhoea as a special case and list some of the major pathogens and the toxins associated with this devastating disease. The damage inflicted by pathogens on their hosts is the result of direct and indirect collateral effects resulting from the activity of virulence factors performing specific functions involved in pathogenesis.

It is the different types of damage caused which result in the symptoms of disease which allow diagnosis and implementation of appropriate treatment and control measures.

The impact on the host of microbial damage depends very much on the tissue involved. Damage to muscle in the shoulder or stomach wall, for instance, may not be serious, but in the heart the very existence of the host depends on a strong muscle contraction continuing to occur every second or so, and here the effect of minor functional changes may be catastrophic. The central nervous system CNS is particularly vulnerable even to slight damage.

The passage of nerve impulses requires normal function in the neuronal cell membrane, and viruses especially have important effects on cell membranes. Also a degree of cellular or tissue oedema that is tolerable in most tissues may have serious consequences if it occurs in the brain, enclosed in that more or less rigid box, the skull.

Therefore, encephalitis and meningitis tend to cause more severe illness than might be expected from the histological changes themselves.

Oedema is a serious matter also in the lung. Oedema fluid or inflammatory cell exudates appear first in the space between the alveolar capillary and the alveolar wall, decreasing the efficiency of gaseous exchanges.

Respiratory function is more drastically impaired when fluid or cells accumulate in the alveolar air space. The effect of tissue damage is much less in the case of organs, such as the liver, pancreas or kidney, which have considerable functional reserves.

More than two-thirds of the liver must be removed before there are signs of liver dysfunction. Cell damage has profound effects if the endothelial cells of small blood vessels are involved. The resulting circulatory changes may lead to anoxia or necrosis in the tissues supplied by these vessels. Here too, the site of vascular lesions may be critical, effects on organs such as the brain or heart having a greater impact on the host, as discussed above.

Rickettsiae characteristically grow in vascular endothelium and this is an important mechanism of disease production. By a combination of direct and immunopathological factors, there is endothelial swelling, thrombosis, infarcts, haemorrhage and tissue anoxia. This is especially notable in the skin and forms the basis for the striking rashes in typhus and the spotted fevers.

These skin rashes, although important for the physician, are less important for the patient than similar lesions in the CNS or heart. It is damage to cerebral vessels that accounts for the cerebral disturbances in typhus; involvement of pulmonary vessels causes pneumonitis, and involvement of myocardial vessels causes myocardial oedema.

For example, in Q fever, rickettsiae sometimes localise in the endocardium, and this causes serious complications.

Sometimes an infectious agent damages an organ, and loss of function in this organ leads to a series of secondary disease features. The signs of liver dysfunction are an accepted result of infections of the liver, just as paralysis or coma is an accepted result of infection of the CNS. There are many diseases of unknown aetiology for which an infectious origin has been suggested. Sometimes it is fairly well established that an infectious agent can at least be one of the causes of the disease, but in most instances it is no more than a hypothesis, with little or no good evidence.

For conditions as common and as serious as multiple sclerosis, cancer and rheumatoid arthritis, it would be of immense importance if a microorganism were incriminated, since this would give the opportunity to prevent the disease by vaccination or treat it with anti-microbials. For example, Borna disease BD has classically been described as a chronic, progressive meningoencephalomyelitis, causing both neurological and behavioural symptoms in horses and sheep. Experimental infection of tree shrews Tupaia glis with BD virus however results in very little overt disease, but afterwards the male is no longer able to enact the ritual courtship behaviour, which as students well know is an essential preliminary to mating in all primates.

Thus it can be said that infection with BD virus renders the male psychologically sterile. Presumably the virus in some way alters the functioning of neurons concerned in this particular pathway. All other behavioural and physiological aspects appear normal. Since the aetiology of such diseases raises interesting problems in pathogenesis, the present state of affairs is summarised in Table 8.

Causal connections between infection and disease states are particularly difficult to establish when the disease appears a long time after infection. It was not too difficult to prove and accept that the encephalitis that occasionally occurs during or immediately after measles was due to measles virus. But it was hard to accept that a very rare type of encephalitis subacute sclerosing panencephalitis or SSPE , occurring up to 10 years after apparently complete recovery from measles, was also due to measles virus and this was only established after the eventual isolation of a mutant form of measles virus from brain cells.

The disease Kuru occurred in New Guinea and was transmitted from person to person by ritual cannibalism. The incubation period in man appears to be 12—15 years, and the disease was caused by an infectious proteinaceous agent known as a prion that grew in the brain.

This was established when the same disease appeared in monkeys several years after the injection of material from the brain of Kuru patients. A similar agent termed the scrapie agent infects sheep, cattle, mice and other animals and also has an incubation period representing a large portion of the lifespan of the host. If in a slow infection, the microorganism that initiated the pathological process is no longer present by the time the disease becomes manifest, then the problem of establishing a causal relationship will be much greater.

This may possibly turn out to be true for diseases like multiple sclerosis and rheumatoid arthritis. Liver cancer in humans and certain leukaemias in mice, cats, humans and cattle can be caused by slow-type virus infections. Cancer or leukaemia appears as a late and occasional sequel to infection. The virus, its antigens or fragments of its nucleic acid are often detectable in malignant cells.

One important factor that often controls the speed of an infectious process and the type of host response is the rate of multiplication of a microorganism. Often the rate of multiplication in the infected host, in the presence of anti-microbial and other limiting factors, and when many bacteria are obliged to multiply inside phagocytic cells, is much less than the optimal rate in artificial culture.

A microorganism with a doubling time of a day or two will tend to cause a more slowly evolving infection and disease than one that doubles in an hour or less Table 8. It is uncommon for an infectious agent to cause exactly the same disease in all those infected. Asymptomatically infected individuals who may continue to shed pathogen are important because they are not identified, move normally in the community, and play an important part in transmission.

This chapter deals with demonstrable cell and tissue damage or dysfunction in infectious diseases. This is distinct from fever or a specific complaint such as a sore throat and, although it is difficult to define and impossible to measure, we all know the feeling.

It can precede the onset of more specific signs and symptoms, or accompany them. Sometimes it is the only indication that an infection is taking place but almost nothing is known of the basis for this feeling. Soluble mediators of immune and inflammatory responses, such as interleukin-1 IL-1; see Glossary or other cytokines doubtless also play a part.

Several cytokines induce release of prostaglandin E2 which, in addition to its effect on fever, reduces the pain threshold in neurons, and this could account for aches and pains. Before giving an account of the mechanisms by which pathogens induce damage in the host, it is important to remember that many infectious agents cause little or no damage. Indeed, it is of some advantage to the microorganism to cause minimal host damage, as discussed in Chapter 1.

Many virus infections fall into this category. Thus, although infection with rabies or measles viruses nearly always causes disease, there are many enterovirus, reovirus and myxovirus infections that are typically asymptomatic. Even viruses that are named for their common association with disease poliomyelitis, influenza, Japanese encephalitis may also be associated with infections in which an antibody response is the only sign of the presence of the pathogen, and tissue damage is too slight to cause detectable illness.

There is a tendency for persistent viruses to cause no more than minor or delayed cellular damage during their persistence in the body, even if the same virus has a more cytopathic effect during an acute infection, e.

A few viruses are remarkable because they cause no pathological changes at all in the cell, even during a productive infection in which infectious virus particles are produced. For instance, mouse cells infected with lymphocytic choriomeningitis LCM see Glossary or murine leukaemia virus show no pathological changes. The recently identified Torque Tenoviruses TTVs are ubiquitous in the human population and appear to establish persistent infections; however, no concrete association with any disease has been demonstrated.

Throughout the life of the animal, virus and viral antigens are produced in the cerebellum, liver, retina, etc. But sometimes there are important functional changes in infected cells which lead to a pathological result. For example, the virus infects growth-hormone-producing cells in the anterior pituitary. Although the cells appear perfectly healthy, the output of growth hormone is reduced, and as a result of this, suckling mice fail to gain weight normally and are runted.

As discussed previously, there are many millions of commensal bacteria which make up the microbiota, which serve important functions for their host. Of course, these bacteria are not typically involved in causing damage. Bacteria such as meningococci and pneumococci, whose names imply pathogenicity, spend most of their time as harmless inhabitants of the normal human nasopharynx: only occasionally do they have the opportunity to invade tissues and give rise to meningitis or pneumonia.

However, when bacteria invade tissues, they almost inevitably cause some damage, and this is also true for fungi and protozoa. Some of the damage may not be severe in nature. For example, Treponema pallidum produces no toxins, does not cause fever and attaches to cells in vitro without harmful effects. Leprosy and tubercle bacilli eventually damage and kill the macrophages in which they replicate, but pathological changes are to a large extent caused by indirect mechanisms see below.

In patients with untreated lepromatous leprosy, the bacteria in the skin invade blood vessels, and large numbers of bacteria, many of them free, may be found in the blood. Mycobacterium leprae can be regarded as a very successful parasite that induces very little host response in these patients, even when the bloodstream is invaded.

Cell and tissue damages are sometimes due to the direct local action of the microorganism. However, in many cases it is not clear how the death of cells results from virus infection. Virus infections result in a shutdown of RNA synthesis transcription , protein synthesis translation and DNA synthesis in the host cell, but often these are too slow to account for the death of the cell. After all, cells like neurons never synthesise DNA, and the half-life of most proteins and even RNAs is at least several hours.

A possible alternative mechanism is the alteration of the differential permeability of the plasma membrane. Viruses do alter membrane permeability, but the unresolved question is whether or not this is responsible for the death of the cell or whether it is merely an after effect. This is the natural process by which the body controls cell numbers and rids itself of superfluous or redundant cells during development.

Cells do not disintegrate but round up and are then removed by phagocytes. Apoptosis in virus infections can be regarded as a host strategy for destroying infected cells.

The chromatin condenses round the edge of the nucleus and a cellular endonuclease cleaves the DNA into — base pair fragments. The cell membrane forms blebs but stays intact while the cell as a whole breaks up into smaller bodies. The suicide process is more controlled, almost more dignified, than mere disintegration and necrosis.

In the latter there is early loss of membrane integrity, spillage of cell contents and random break-up of DNA. Some viruses encode proteins whose function is to inhibit apoptosis, so allowing the virus to replicate and new virions to be produced before the cell dies.

Conversely some viruses appear to induce apoptosis, perhaps as a means of evading the immune response; apoptotic cells are not efficiently recognised by the immune system. There are two more characteristic types of morphological change produced by certain viruses, and these were recognised by histologists more than 50 years ago.

The first are inclusion bodies, parts of the cell with altered staining behaviour which develop during infection. Herpes group viruses form intranuclear inclusions, rabies and poxviruses intracytoplasmic inclusions, and measles virus both intranuclear and intracytoplasmic inclusions.

The second characteristic morphological change caused by viruses is the formation of multinucleate giant cells. This fusion mimics the fusion event that occurs when an enveloped virus binds to the surface of an uninfected cell and the virus membrane and cellular membranes fuse, so allowing entry of the virus genome and proteins to the cell.

This cell—cell fusion can also be observed following infection with paramyxovirus measles, respiratory syncytial virus RSV and certain herpes viruses. Before leaving the subject of direct damage by viruses, one supreme example will be given.

Here the direct damage is of such a magnitude that the susceptible host dies a mere 6 h after infection. If Rift Valley Fever virus, an arthropod-borne virus infecting cattle, sheep and man in Africa, is injected in very large doses intravenously into mice, the injected virus rapidly infects nearly all hepatic cells. Hepatic cells show nuclear inclusions within an hour and necrosis by four hours. As the single cycle of growth in hepatic cells is completed, massive liver necrosis takes place, and mice die only 6 h after initial infection.

The host defences in the form of local lymph nodes, local tissue phagocytes, etc. Direct damage by the replicating virus destroys hepatic cells long before immune or interferon responses have an opportunity to control the infection. The experimental situation is artificial, but it illustrates direct and lethal damage to host tissues after all host defence mechanisms have been overwhelmed.

Most rickettsiae and Chlamydia damage the cells in which they replicate, and it is possible that some of this damage is due to the action of toxic microbial products. This action, however, is confined to the infected cell, and toxic microbial products are not liberated to damage other cells. Mycoplasma see Table A. The mechanism is not clear. If a complete lawn of mycoplasma covers the surface of the host cell, some effect on the health of the cell is to be expected, but it is possible that toxic materials are produced or are present on the surface of the mycoplasma.

Intracellular bacterial pathogens generally damage the cells in which they replicate see Chapter 4. Listeria , Brucella and Mycobacteria are specialists at intracellular growth, and the infected phagocyte is slowly destroyed as increasing numbers of bacteria are produced in it. Bacteria such as staphylococci and streptococci grow primarily in extracellular fluids but can also invade and proliferate in epithelial and endothelial cells.

They are also ingested by phagocytic cells, and virulent strains of bacteria in particular have the ability to destroy the phagocyte in which they find themselves or can avoid killing and proliferate within the phagocytes, as described in Chapter 4. Many bacteria cause extensive tissue damage by the liberation of toxins into extracellular fluids. Various toxins have been identified and characterised. Most act locally, but a few cause pathological changes after spreading systemically through the body.

Dental caries provides an interesting example of direct pathological action. Colonisation of the tooth surface by Streptococcus mutans leads to plaque formation, and the bacteria held in the plaque utilise dietary sugar and produce acid. Locally produced acid decalcifies the tooth to give caries. Caries, arguably the commonest infectious disease of Western man, might logically be controlled by removing plaque, withholding dietary sugar, or vaccinating against S.

However, fluoride in the water supply or in toothpaste has been the method of choice and has been very successful. It acts by making teeth more resistant to acid. This is a huge and growing part of our subject and we need to define the term toxin, a task which is more difficult than one might think. This view is too embracing, because it includes proteins of doubtful significance in disease and also too restrictive, because it excludes non-protein toxic complexes such as endotoxin.

Another suggestion is that toxin must include all naturally occurring substances of plant, animal, bacterial or whatever origin which, when introduced into a foreign host, are adverse to the well-being or life of the victim. This, too, is unsatisfactory because some substances — potent toxins within the scope of this definition — are being used in some contexts as therapeutic agents!

Perhaps it is pointless to strive for an all-embracing definition, although the obvious differences between bacterial and fungal toxins warrant the continued use of the appropriate prefix. For example, bacterial toxins are usually of high molecular weight and hence antigenic, whereas fungal toxins tend to be low molecular weight and not antigenic. The problem of definition is compounded because there are substances aggressins which help to establish an infective focus as well as those whose action is uniquely or largely responsible for the disease syndrome.

Also there are substances known to be produced by bacteria in vitro , whose properties on a priori grounds make them potential determinants of disease, but which have not been shown to play a role in vivo.

For many toxins, there is considerable understanding of the genetic basis of toxin expression, secretion, assembly and activity, the resolution of the three-dimensional structure of toxins, and their biochemical modes of action. We now know a great deal about the spread of some virulence determinants in bacterial populations via bacteriophages and other transmissible genetic elements, the conditions under which toxins are expressed both in vitro and in vivo , how to disassemble complex protein toxins and form chimeric derivatives of known and potential use as therapeutic agents, and how to use some of the deadliest poisons known to man in treating certain physiological disorders.

Elucidation of biochemical modes of action has resulted in toxins being used increasingly as important tools for the dissection of cell biological processes.

Also, some new insights as to the role s of toxins in disease causation have been developed. The latter is the result of using isogenic toxin-deficient mutants in vivo , using more relevant biological test systems and concentrating more on the effects of sublethal doses of toxin and less on the effects of injecting a toxin bolus into some animal. It is beyond the scope of this book to attempt to cover all these subjects, so only an outline treatment will be given with some examples.

These are either secreted by or released upon lysis from both Gram-positive and Gram-negative bacteria, and historically referred to as exotoxins. They are proteins, some of which are enzymes. When liberated locally they can cause local cell and tissue damage. Those that damage phagocytic cells and are therefore particularly useful to the microorganism have been described in Chapter 4. Those that promote the spread of bacteria in tissues have been referred to in Chapter 5. A selection of some protein toxins follows.

Helicobacter pylori is a specific human pathogen affecting billions of people worldwide. It is transmitted via the orofaecal route and colonises the seemingly inhospitable niche of the stomach. An essential virulence factor of H. As noted in Chapter 2, it is important in local neutralisation of stomach acidity thereby allowing H. However, urease is now considered by some as a toxin which acts outside cells, since NH 3 , the product of urease activity, is toxic to cells.

Proteases and hyaluronidases , which help the spread of bacteria through tissues, have already been mentioned in Chapter 5. Here we consider toxins which act on extracellular substances and are responsible for many of the main characteristics of the diseases caused by the infecting organism.

Pseudomonas aeruginosa elastase, and one of at least six proteases of Legionella pneumophila , both induce fibrinopurulent exudation in the rat lung a model for P. These characteristics almost certainly arise from the release of oligopeptides from extracellular matrix components of the host which are chemotactic for leucocytes and fibroblasts. The L. The disease is characterised by a region of erythema which usually begins around the mouth and, in 1—2 days, extends over the whole body.

The most striking feature of the disease is that the epidermis, although apparently healthy, can be displaced and wrinkled like the skin of a ripe peach by the slightest pressure. Soon large areas of epidermis become lifted by a layer of serous fluid and peel at the slightest touch.

Large areas of the body rapidly become denuded in this way and the symptoms resemble those of massive scalding. The toxin causes cleavage of desmoglein 1, a desmosomal adhesion molecule desmosomes are specialised cell membrane thickenings through which cells are attached to each other in the stratum granulosum.

Some toxins destroy membranes by virtue of their proteolytic activities, and some by their ability to degrade lipid components, while others are pore-forming or detergent-like in their mode of action. In addition to their action on protein components of lung connective tissue referred to above, P. This is the probable reason for the haemorrhage associated with lung infections caused by these pathogens, i. A large number of bacterial enzymes are phospholipases, some of which, but by no means all, are important toxins.

It is strictly anaerobic and occurs as a normal inhabitant in the large intestines of man and animals; its spores are ubiquitous in soil, dust and air. After abortions, particularly in the old days before antibiotics, intestinal clostridia often gained access to necrotic or devitalised tissues in the uterus and set up life-threatening infections.

Invasion of the blood was common and soon resulted in death, the clostridia localising and growing in internal organs such as the liver after death. It is dermonecrotic, haemolytic a feature seen mainly in tissues close to the focus of infection but sometimes responsible for large-scale intravascular haemolysis in infected patients , causes turbidity in lipoprotein-rich solutions and is lethal.

While it is still true that these activities are all due to one molecular species, they are not as was once thought different expressions of the one enzymic activity. Historically, C. It is of undoubted importance in gas gangrene. Toxoid prepared by formalin-treated toxin will protect sheep against infection caused by C.

The activation of the arachidonic acid cascade results in the production of leukotrienes increasing vascular permeability , prostaglandins and thromboxanes causing inflammation, muscle contraction and platelet aggregation.

This toxin also upregulates expression of endothelial leucocyte adhesion molecule-1 ELAM-1 , intercellular adhesion molecule-1 ICAM-1 and neutrophil chemoattractant-activator IL-8, thereby impairing delivery of phagocytes to the site of infection.

Clostridial illness can be mild or very severe according to the extent of bacterial spread, and the quantity of toxins that are formed and absorbed. Since the bacteria grow and produce their toxins only in devitalised tissues, the most important form of treatment is to remove such tissues. Clostridia are strictly anaerobic and exposure of the patient to hyperbaric oxygen pure oxygen at 2—3 atmospheres in a pressure chamber has been found useful in addition to chemotherapy.

It has activity on a number of different cell types including erythrocytes and may contribute to iron acquisition by release of haemoglobin from red blood cells. Recently, it has been reported to play a role on biofilm production by Staphylococcus aureus. It is noteworthy that in contrast to bovine mastitis strains of S.

These data imply that beta toxin may be more important in some animal infections in comparison to humans. A variety of bacterial pathogens produce specialised pore-forming toxins with an array of receptors, cell specificities and activities. Here we will discuss some selected examples. They are lethal, cardiotoxic, antigenically related, and their lytic and lethal activities are blocked by cholesterol. Interaction with cholesterol is thought to be the key primary event in their interaction with susceptible membranes, which leads to the impairment of the latter; cholesterol plays no further part in the subsequent damage process.

However, the role of cholesterol has been interpreted in terms of mediating the oligomerisation process illustrated in Figure 8. Examples of cholesterol-binding cytolysins CBCs from pathogenic species include streptolysin O and S made by streptococci, perfringolysin O made by C.

Despite the similarities which warrant their inclusion in the same toxin group, they play entirely different roles in disease causation by the organisms expressing these toxins. A good example to go into more detail is PLY. Pore formation by pore-forming toxins.

Newly synthesised proteins are soluble. On interaction with cell membranes they undergo conformational changes which allow reorganisation on and insertion into target cell membranes. Cholesterol is involved as primary receptor or mediator of aggregation for the CBC group.

This protein is produced by the pathogen S. PLY is different from all other members of this group in that it is not actively secreted by the pathogen but remains in the cytoplasm until released by lysis of the pneumococcus. This toxin is a four-domain molecule which oligomerises and forms a pore after cholesterol binding. It possesses a number of different functions in pathogenesis and has haemolytic activity and induces inflammation of the lung conferring the ability to replicate in the lung and invade the bloodstream, and altering alveolar permeability, also inhibiting cilial beat in respiratory mucosa.

An important function is the activation of the classical pathway of complement which presumably assists evasion of complement activity directed towards bacterial cells. PLY can influence the expression of a number of host genes and multiple host-associated signal transduction pathways and is considered to be a neurotoxin.

PLY has also been implicated in causing sensorineural deafness associated with meningitis caused by the pneumococcus Figure 8. The effect of PLY on the hair cells of the inner ear of a guinea pig. Hearing depends on the transmission to the hair cells of pressure waves generated in the fluid-filled chamber scala tympani of the cochlea.

This causes lateral displacement of the hairs. Inelastic links between hairs in different rows results in membrane deformation, opening of ion channels and influx of ions. This generates an action potential in the underlying auditory nerves. Attempts to develop protective anti-pneumococcal vaccines have hitherto been based on the type-specific capsular polysaccharides.

Unfortunately, there are at least 90 known types and current vaccine preparations comprise a blend of polysaccharides from some 23 types. Currently, efforts to develop a broadly effective vaccine based on genetically engineered PLYs fused to other S.

This group of toxins has been designated RTX repeats in toxin toxins by virtue of a common structural feature — the presence of an array of a nine amino acid repeat ca.

They constitute the largest group of bacterial pore-forming toxins and are widespread among Gram-negative pathogens. Leukotoxin from Pasteurella haemolytica exhibits narrow target cell and host specificities; it specifically kills ruminant leucocytes and is important in bovine pneumonic pasteurellosis. This toxin is unique among this group in that it is a large bifunctional toxin: it has both haemolytic Hly and adenylate cyclase AC activities, hence the designations AC-Hly, AC toxin, CyaA, and is known to be important in the early stages of respiratory tract colonisation.

Strictly it is the haemolysin part of the molecule which belongs to the RTX family and its main function appears to be in translocation of the AC moiety into the cell where cAMP levels are elevated with ensuing pathophysiological sequelae. Staphylococci produce a range of toxins, some of which we have already met. Ultimately the interaction leads to upregulation of ADAM metalloprotease activity leading to the cleavage of E-cadherin and disruption of epithelial barrier function.

This in turn leads to acute lung injury. PSMs are amphipathic alpha helical peptides with their own unique secretory transport system, and they have potent activity on neutrophils after phagocytosis, and contribute to biofilm formation, dissemination, colonisation and inter-species competition. These comprise two proteins, only one of which is toxic but the other is necessary at some stage for manifestation of toxicity. A good example is the staphylococcal leukocidins which belong to a very large family of binary leukocidins.

Each leukocidin consists of two proteins — S so called because it elutes slowly and F it elutes fast from an ion-exchange column. S binds first to cell receptors, several of which have been recently identified important in defining target cell specificity , followed by F which acts synergistically with S to create functional pores in the target membrane.

There are at least six class S proteins and five class F proteins which can give rise to ca. Although various S—F combinations exhibit different target cell specificities, most are active against PMNs.

For example, Panton—Valentine leukocidin is highly active against human PMNs binding to the human complement receptor C5aR and causes release of leukotriene B4, IL-8, histamine and tissue degradative enzymes, which likely accounts for some of the respiratory tissue damage and severe symptoms associated with necrotising pneumonia.

In addition leukocidin ED binds to the CCR5 receptor on neutrophils and T-lymphocytes, leading to disruption of phagocytosis which promotes survival in mouse models of infection. Many toxins have intracellular targets. There is intense interest in seeking to understand the mechanism s of uptake of the active moieties of toxins whose targets are intracellular.

To reach an intracellular target, a protein must first be translocated across the cytoplasmic membrane. There are at least three ways in which this can be achieved: self-translocation across cytoplasmic membrane, direct injection and receptor-mediated endocytosis. The best example of self-translocation across cytoplasmic membrane known to date: the invasive adenylate cyclase of B.

A good example is the P. There are several variations on the receptor-mediated endocytosis theme reflecting the structure of the toxins; in some cases the process involves the subversion of normal processes used by the host cell to regulate movement and organisation of cellular membranes and substituent components.

Toxins first bind to their respective receptors and become internalised via coated pits, vesicles or caveolae, into endosomes from which they still must escape into the cytoplasm. Three types of toxin with intracellular targets have been recognised, reflecting their genetic origin. Some toxins consist of a single peptide, the product of a single gene, which undergoes post-translational modification into A and B fragments which are covalently linked Figure 8. A study in mice found that animals given antibiotics which kill gut bacteria became less anxious, and when their gut bacteria was restored, so was their anxiety.

Mice given antibiotics also showed changes in their brain chemistry that have been linked to depression. The researchers said they suspect the bacteria are producing chemicals that can access and influence the brain. If gut bacteria play a role in human behavior, its possible that therapies that aim to restore normal gut flora, such as probiotics, may be helpful in correcting behavior and mood changes in people with gastrointestinal diseases, according to the researchers.

However, it's not clear if the results apply to people. Abnormal gut bacteria in infants may be one cause of colic , or excessive crying, recent research suggests. In the study, colicky babies who cry for more than three hours a day without a medical reason had a distinct bacterial "signature": They had higher numbers of bacteria from a group called Proteobacteria in their guts compared to babies without colic.

Proteobacteria include bacteria known to produce gas, which may cause pain in infants and lead to crying, the researchers said. These abnormities disappeared after the first few months of life, which suggests they are temporary. However, this study was small and conducted for just a few months, so additional, longer studies are needed to confirm the results.

Rachael has been with Live Science since Lysogenic cycles are utilized by specific types of viruses to ensure viral reproduction, but they also need the second major method of viral reproduction, the lytic cycle, as well.

The lytic cycle, considered the primary method of viral replication, results in the actual destruction of the infected cell.

Upon destruction of the infected cell, the new viruses, which have developed after undergoing biosynthesis and maturation, are free to infect other cells. The lytic cycle is characterized by the breakdown of the bacteria cell wall intracellularly.

The viruses cause disruption of the bacterial cell by producing enzymes which facilitate this process. Specifically, the bacterium, Vibrio cholerae , is transformed into a toxic strain upon infection with the bacteriophage. This bacterium is then able to produce a cholera toxin, the cause of the disease cholera.

Lysogenic and lytic cycles : Schematic of lysogenic and lytic cycle utilized by viruses to ensure viral reproduction. Siderophores produce specific proteins and some siderophores form soluble iron complexes to aid in iron acquisition for survival. Compare and contrast the role of various siderophores in pathogenecity, including: yersiniabactin, enterobactin and ferrichromes. Siderophores are specific types of molecules utilized by microorganisms to obtain iron from the environment.

Specifically, in regards to pathogenicity, organisms that exhibit the ability to produce siderophores release these iron-specific molecules and scavenge iron from their hosts organisms. The siderophores are then utilized by the pathogen to obtain iron. Therefore, siderophores are chelating agents that bind the iron ions. The ability of pathogens to obtain iron from the host is essential for survival because the iron is limited in the host environment, in particular, the host tissues and fluids.

The complexes then generally bind to the cellular membrane using cell specific receptors. They are transported across the membrane utilized for the necessary processes.

However, there are differences in the mechanisms employed by various sideorophobes to obtain iron and the specific type of siderophore utilized varies. The pathogenic bacteria, Yersinia pestis, Yersinia pseduotuberculosis, and Yersinia enterocolitica have the ability to produce a siderophore called yersiniabactin. Pathogenic yersinia is responsible for numerous diseases including the bubonic plague.

The ability of pathogenic Yersinia to establish and spread disease is based on its ability to obtain iron for fundamental cellular processes. The complex is then translocated through the membrane via membrane-embedded proteins and iron is released from the yersiniabactin.

The iron will then be utilized in numerous cellular processes. Pathogenic bacteria such as Escherichia coli and Salmonella typhimurium have the ability to produce a siderophore called enterobactin. The complex is then transported intracellularly via an ATP-binding cassette transporter.

Due to the high-binding affinity of enterobactin, the bacteria require a highly specific enzyme, ferrienterobactin esterase, to cleave the iron from the complex. The iron released from the complex will then be utilized in metabolic processes.

Another type of siderophore produced by pathogenic fungi includes a ferrichrome. Fungi that have been shown to produce ferrichromes include those in the genera Aspergillus, Ustilago, and Penicillum.

The ferrichrome allows for formation of a ferrichrome-iron complex which can then interact with a protein receptor on the cell surface. The ferrichrome promotes iron transport within the organism to allow metabolic processes to occur.

The discovery and identification of siderophores have allowed for the development of treatments targeting these siderophore-iron complexes. By targeting these complexes, the pathogenic microorganisms can be targeted by inhibiting necessary cellular processes.

The production and importance of these siderophores to pathogenic organisms is key to their survival. Privacy Policy. Skip to main content. Search for:. Damaging Host Cells. Toxins Microorganisms produce poisonous substances called toxins. Learning Objectives Describe the major toxin types bacterial toxins and mycotoxins and their mechanisms of action. Key Takeaways Key Points Microbial toxins may include those produced by the microorganisms bacteria i.

Bacterial toxins can include both endotoxins and exotoxins, which vary in mechanism of action and are species -specific. Mycotoxins can be classified into numerous categories and are not species-specific because the same mycotoxin can be produced by different fungal species.

Key Terms endotoxin : Any toxin secreted by a microorganism and released into the surrounding environment only when it dies. Direct Damage Direct damage to the host is a general mechanism utilized by pathogenic organisms to ensure infection and destruction of the host cell. Learning Objectives Describe the different processes used by pathogens to damage the host and ensure infection.

Key Takeaways Key Points Pathogenic organisms must have mechanisms in place to evade attack by the immune system. Pathogens can produce enzymes that disrupt normal tissue and allow for further invasion into the tissues. Pathogens can produce toxins that interfere with protein function deemed necessary by the host cell for proper maintenance.

Key Terms diphtheria : A disease of the upper respiratory tract caused by a toxin secreted by Corynebacterium diphtheriae. Type IV secretion systems use a process which is similar to the bacterial conjugation machinery. Type IV secretion systems require attachment to the host cell by direct cell-to-cell contact or via a bridge-like apparatus.

Type IV secretion systems can be used to both transport and receive molecules. Type III secretion systems requires a large protein complex to ensure proper transfer of secretory molecules. Key Terms peptidoglycan : A polymer of glycan and peptides found in bacterial cell walls. Plasmids and Lysogeny Both plasmids and lysogeny are used by bacteria and viruses to ensure transfer of genes and nucleic acids for viral reproduction.

Learning Objectives Distinguish between plasmids and lysogeny in regards to pathogenecity. Plasmids are responsible for horizontal gene transfer which promotes the development of antibiotic resistance in bacterium.

Lysogeny is a major method of viral reproduction characterized by the integration of viral nucleic acids in the bacterium genome.