Program Director, Stony Brook University School of Medicine
Figure 14-3 depicts this process as an antigenic switch from a -pilin type to an -pilin type gastritis diet из pantoprazole 40 mg on line. Pilin diversification depends not only on the mere number of pilS genes but also on the fact that small stretches of pilS sequence can be recombined into the expression locus resulting in chimeric pilin types gastritis symptoms hunger discount pantoprazole 20 mg with mastercard. Such an event is depicted in Figure 14-3 as the formation of a pilE hybrid between the - and -alleles gastritis diet cooking buy 20 mg pantoprazole visa. Note that this process occurs through a mechanism called gene conversion symptoms of gastritis flare up buy 40 mg pantoprazole with amex, in which the pilS alleles act as donors of new genetic information but are not altered themselves. The result is a virtually infinite variety of pilin serotypes that can be expressed using only a limited number of pilS alleles. In this process, the expression of a particular gene product is turned on or off at high frequency. An example of this mechanism is the phase variation of type I fimbriae expression in Escherichia coli. In the "on" state, the promoter element is oriented so that transcription of the fimbrial subunit 6 repeats gene, fimA, can take place. Inversion of the element (shown in blue) orients the promoter in a direction divergent to that of fimA. Analogous inversion systems control the expression of flagellar types in Salmonella and pilus expression in other Gram-negative pathogens. The second mechanism of phase variation is associated with the somewhat unusual occurrence of short nucleotide repeats at the 5 ends of genes. Multiple copies of complete opa genes (which each encode different Opa antigenic variants) are scattered throughout the genome. Gain or loss of these elements alters the translational reading frame of the gene and determines whether the intact protein can be made. The sequences have been modified and shortened to demonstrate the mechanism succinctly. Chapter 14: Neisseriae: Gonococcus and Meningococcus 183 carrying six copies of the element. In this way, gonococci can turn on or off the expression of any of opa genes independently. Analogous phase variation mechanisms have been shown to operate in a number of important surface molecules in other Gramnegative pathogens. The only common feature is that the number of nucleotides of the repeat element is not three, nor is it divisible by three. Because the genetic code operates through trinucleotide codons, deletion or addition of a three base pair repeat would not change the reading frame. Another way that slipped strand mispairing can disrupt gene expression is when it occurs in the promoter element of a gene. Phase variation can represent a simplified form of antigenic variation in which a specific protein antigen is either expressed or not (as opposed to multiple different antigenic types of a protein), but gain or loss of molecules also has important functional consequences unrelated to immune pressure. The widespread distribution of this form of phase variation among microbes suggests that it is biologically important and that there is an evolutionary advantage to existing as a heterogeneous population. Movement into the urethra or through the cervix can be aided by menses, secretions, or urethral or uterine contractions. IgG found in secretions may indicate leakage of the antibody from serum onto the mucosal surface, whereas most of the IgA is actively secreted into the lumen of the genital tract. Gonococci produce an extracellular protease that specifically cleaves IgA1 but not IgA2 in the hinge region. This property is also present in other bacteria that inhabit mucosal epithelia, such as Haemophilus influenzae and certain streptococci. The protease also may have activity on gonococcal surface proteins and may help the organisms escape phagocytosis by removing the Fc end of the immunoglobulin from gonococcus-bound IgA molecules. Because the Fc region is the portion recognized by phagocytes, the organisms may be less likely to be taken up by white blood cells when this portion of the immunoglobulin molecule is removed. What is known about invasion of epithelial cells by gonococci is assumed from studies with in vitro organ culture of human fallopian tubes and from primary human cervical epithelial cells. Two major types of cells compose the epithelial mucosal surface of human fallopian tubes: ciliated cells and nonciliated cells. The nonciliated cells have fingerlike processes, called microvilli, on their luminal surface. Ciliary activity is thought to be important in moving the fertilized egg from the fallopian tube to the uterus and in providing a flushing mechanism for clearing mucus and bacteria from the mucosal surface. Gonococci are then internalized by these "nonprofessional" phagocytes by a process termed parasite-directed endocytosis. Inside the nonciliated cells, gonococci are sheltered from antibodies, professional phagocytes, and antibiotics that do not enter human cells well. The inflammatory response in the male urethra is probably responsible for local symptoms such as pain on urination (dysuria) and urethral discharge of pus. It is noteworthy that these symptoms do not distinguish gonococcal urethritis from that caused by other genital pathogens, like the chlamydiae (see Chapter 27). However, the urethral discharge in gonorrhea tends to be more copious, thick, and greenish yellow, and the pain is more intense. Although, as noted, women with gonococcal cervicitis are more often asymptomatic than are men with urethritis, women can experience dysuria, dyspareunia (pain on intercourse), discharge, or genital discomfort. Scanning electron micrograph of human fallopian tube tissue 20 hours after infection with Neisseria gonorrhoeae. Notice that gonococci attach almost exclusively to the surface of nonciliated cells. Ciliated cells sloughed from the surface of the mucosa appear at the left and center of the photomicrograph, whereas intact ciliated cells are seen at the top and right.
These images of selected viruses were obtained using either cryoelectron microscopy and three-dimensional computer processing or transmission electron microscopy gastritis diet zone cheap pantoprazole 20 mg on-line. Semliki Forest virus gastritis diet майл order pantoprazole canada, influenza virus gastritis diet чернобыль buy pantoprazole 40mg online, paramyxovirus gastritis symptoms spanish purchase pantoprazole without a prescription, and smallpox virus are enveloped viruses. The envelope of Semliki Forest virus is hidden by a dense outer shell formed by the major envelope glycoproteins. The envelope glycoproteins of influenza virus, paramyxovirus, and smallpox virus are less densely arrayed, and their envelopes have less defined structure. Note the characteristic wiggly helical nucleocapsid of the paramyxovirus and the complex structure of smallpox virus. The delivery system consists of structural components used by the virus to survive in the environment and bind to host cells. The delivery system of a virus protects it against degradation in the environment and contains structures used to bind to target cells in the host. The payload of a virus contains the genome and enzymes necessary to initiate the first steps in virus replication. An eminent scientist once characterized a virus as "a piece of bad news wrapped in a protein coat. The smallest viral genomes encode three or four proteins, and the largest encode more than 100 structural proteins and enzymes. The number of proteins encoded may be greater than predicted from the size of the nucleic acid. The viral nucleic acid is surrounded by a capsid, a single- or double-layer protein shell. Together, the nucleic acid and the capsid are often referred to as the nucleocapsid. Capsids are composed of subunits (sometimes called "capsomers") arranged in symmetric patterns. Each capsid subunit has the capacity to bind to other subunits in specific ways; these physical interactions between subunits permit the subunits to selfassemble to form the virus capsid. Viral capsid proteins are arranged in two basic structural patterns, icosahedral and helical. Viral glycoprotein spikes are incorporated into the membrane, the viral nucleocapsid is assembled near the membrane, and budding begins (3). The arrow indicates proteins aligned at regular intervals in the helical nucleocapsid. Viruses with icosahedral symmetry usually have a spherical shape, like a soccer ball. In those viruses, the nucleic acid is packed inside the spherical core and often tightly associated with specific viral capsid proteins. A general feature of viruses with helical symmetry is that the protein subunits of the capsid are bound in a regular, periodic fashion along the nucleic acid. Some of the largest viruses, such as the poxviruses, have complex structural arrangements. Those viruses are called enveloped viruses; viruses without an envelope are called nonenveloped viruses. The viral envelope is composed of virus-specific proteins plus lipids and carbohydrates derived from host cell membranes. In some cases, virus-specific envelope proteins include a matrix (M) protein that lines the inner surface of the envelope and is in contact with the nucleocapsid. M proteins may stabilize the interaction between viral glycoproteins and the lipid envelope, direct the viral genome to intracellular sites of virus assembly, or help in virus budding. Virusspecific envelope glycoproteins protrude from the outer surface of the envelope. The principal viruses that cause disease in humans belong to about a dozen families containing hundreds of species (Table 31-1. Each species may contain many individual strains that differ in virulence and antigenic properties (serotypes). Viruses are classified according to a number of factors, including their structure, the nature of their genome, and their replication strategy, as well as their immunologic properties and the diseases they cause. The structural and genetic diversity of viruses is reflected in the variety of replicative strategies that they employ. Viruses can regulate cellular enzymes, modify cellular structures, and perturb metabolic and signaling pathways. Reoviruses and orbiviruses have 10 segments; rotavirus has 11 segments; Colorado tick fever has 12 segments. Attachment and Penetration the first step in viral infection of target cells is the attachment of the virus to the host cell surface. That step, which is also called adsorption, is initially reversible and results from random collisions between virions and target cells. For enveloped viruses, the attachment protein is usually one of the spikes exposed on the outer surface of the viral envelope, such as the hemagglutinin of influenza virus. Some enveloped viruses, such as the herpesviruses and poxviruses, have more than one type of attachment protein. For nonenveloped viruses, surface-exposed regions of capsid proteins function to mediate virus attachment.
Finally gastritis cats order pantoprazole 40mg on line, there is the growing understanding of exactly how the normal microbiota contribute to human health gastritis causas buy pantoprazole master card, in many cases by altering the host environment in which pathogens can thrive or be kept under control gastritis prevention cheap pantoprazole 20 mg on line. Thus severe gastritis diet plan purchase pantoprazole with a mastercard, the study of microbial pathogens and microbial biology in general remains a rich target area for research and innovations that will have a significant impact on human health. The staphylococci or streptococci of today fit their original descriptions from the end of the 19th century. They include Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus (which almost exclusively causes urinary tract infections), and numerous others. Encounter: Organisms grow on the surface of humans and survive on inanimate surface. During a lifetime, approximately 90% of humans are colonized with at some point with S. Entry: Carriage of staphylococci usually occurs after direct, skin-to-skin contact with another carrier. Infection may also occur after penetration of a contaminated object through the skin. Staphylococci cause skin and soft tissue infections (such as furuncles, abscesses, and necrotizing fasciitis), pneumonia, food poisoning, and toxin-induced diseases (toxic shock and scalded skin syndromes). If the organisms enter the bloodstream, they may cause osteomyelitis, kidney abscesses, or endocarditis. They also secrete virulence factors such as hemolysins, leukocidins, superantigens, and other exotoxins. Diagnosis: Staphylococci have a characteristic appearance on Gram stain, and they are easily isolated on most laboratory media. Treatment: Most strains produce -lactamase (an enzyme that breaks down penicillin). However, some strains express penicillin-binding protein 2a, which also makes the organism resistant to the abovementioned agents (methicillinresistant S. Drainage of abscesses and supportive therapy for hypotension and shock are also critical, nonantimicrobial elements of care. They colonize the anterior nares of 30 to 40% of individuals and may be present on other mucous membranes and the skin. The organism also causes more-frequent and varied types of diseases than perhaps any other human pathogen (see box, Diseases Caused by Staphylococci). The bacteria can produce focal abscesses at almost any site in the body, from the skin (furuncles or "boils") to the lungs (pneumonia), bones (osteomyelitis), kidneys, and heart (endocarditis). In addition, many strains of the bacterium secrete potent exotoxins that can cause signs of illness at sites distant from the bacterial infection. The secreted and cell surface virulence factors produced by staphylococci act locally mainly to help them withstand phagocytosis by neutrophils. For example, clumping factor (also known as bound coagulase) binds fibrin and helps the organism form walled-off abscesses protected from phagocytes. In addition, some factors act systemically to disrupt the normal immune system function. As a result, staphylococci are among the most adaptable of the pathogenic bacteria. They are difficult to eliminate from the human environment, and they are responsible for many community- and hospital-associated infections. Four days later, his condition deteriorated, and he developed fever, chills, and shortness of breath (dyspnea), followed by nausea and vomiting. Initial examination showed significant respiratory distress, no rash, supple neck, no heart murmur, decreased breath sounds in the right lower lung field, no abdominal tenderness, and no focal neurological findings. A Gram stain of organisms grown on blood agar plates from sputum cultures after intubation showed Gram-positive cocci in clusters. The organism was shown to be susceptible to clindamycin, trimethoprim/sulfamethoxazole, tetracycline, linezolid, rifampin, and vancomycin. Despite aggressive treatment, his condition continued to worsen, his skin became mottled, and he developed purpura over his lips and legs that progressed to cover his entire body in 12 hours. Skin purpura is a result of shock and activation/dysregulation of the clotting cascade systemically. Gram stain purple and appear as clusters of grapes (staphylo is derived from the Greek word for grape clusters). This is due to the organism making large numbers of cell-associated virulence factors that cause clotting and adherence to human tissues. Over the next week, she noticed mild swelling, increasing pain, and a small amount of redness at the incision site. Examination revealed a "toxicappearing" young woman who had a sunburnlike rash on her face, mild skin peeling above the eyes, and red eyes and lips. Her blood pressure was 70/50 mm Hg, indicating she was hypotensive, and she had elevated white cells in the blood and a significantly reduced number of platelets. Over the next day, her condition worsened, despite being treated with nafcillin, gentamicin, and supportive care (fluid and electrolytes and vasopressors to maintain blood pressure), and she developed gangrenous toes. A needle was inserted into the site of the previous knee surgery, and 300 mL of serous fluid was removed that cultured positive for S. What are the properties of the organism that prevented it from being cleared by nafcillin The initial lesion was a subcutaneous abscess that was overlooked because of its minimal inflammatory features. It is important in such patients to maintain blood pressure adequately to prevent development of gangrene, as happened with Ms.
Subsequent enzymatic steps yield glucose-6-phosphate symptoms of gastritis back pain discount pantoprazole online master card, which can then be further metabolized gastritis diet advice nhs purchase pantoprazole overnight. A substrate-for instance gastritis lasting weeks buy generic pantoprazole pills, the sugar lactose-is concentrated unchanged inside the cell gastritis diet 17 20 mg pantoprazole visa, which makes the transport of additional molecules energetically unfavorable. To drive the transport of lactose, the cells use energy stored in an electrochemical gradient of protons, the proton motive force. This gradient is generated by the extrusion of protons from the cell, resulting from the oxidation of metabolic intermediates like reduced nicotinamide adenine dinucleotide or by hydrolysis of adenosine triphosphate. Lactose is accumulated intracellularly by coupling its energetically unfavorable transport with the energetically favorable reentry of protons into the relatively alkaline cytoplasm of the cell. Thus, transport of this type takes place via a symport, which requires the simultaneous uptake of positive hydrogen and sugar molecules. Some proteins aid the process by modifying or concentrating substrates in the periplasmic space of Gram-negatives. The periplasmic space also contains nucleotidases, nucleases, peptidases, proteases, and other hydrolytic enzymes. The actual transport process is carried out by membrane-bound carriers, or permeases, which are involved in all three types of transport. The three types of transport in Escherichia coli are facilitated diffusion, group translocation, and active transport with the lac permease. Chapter 3: Biology of Infectious Agents 27 permeases respond to the proton gradient, but we know that they assume different configurations inside and outside the cytoplasmic membrane. Thus, permeases have a high affinity for substrate on the outside and low affinity on the inside. For example, in the much-studied lactose system, cells that lack a functional permease remain impervious to the sugar, even when soaked in concentrations approaching syrup. The three mechanisms of transport are used to different extents by different bacteria. In general, few substrates equilibrate across membranes without the expenditure of energy. Among the energy-requiring mechanisms, group translocations are used to a different extent. All in all, active transport dominates the repertoire of transport mechanisms in bacteria, especially when nutrients must be concentrated from the medium to support cell growth. The phenomenon was first demonstrated by genetic transformation of pneumococci and occurs among other bacteria. In spite of its versatility and range of activities, the cytoplasmic membrane of bacteria is rarely the site of useful antibiotic action (see Chapter 5). Its physical state is unknown and somewhat mysterious, because in the test tube, a solution 100 times more dilute is a gel. One wonders how this can take place without entanglement of the tightly coiled nucleoid. The timing of chromosome replication is a highly regulated process and is coupled to growth and cell division. Free iron is extremely scarce in the blood and many tissues because it is bound by proteins like transferrin or ceruloplasmin. It is essential for the growth of bacteria, and many species that inhabit the human body have developed ingenious mechanisms to obtain the amounts of this element they need for growth. They excrete chelating compounds, known as siderophores, that bind iron with great avidity. Each organism can take up its own particular form of complexed iron; individual complexes are unique enough to be less digestible for other organisms. However, in response to the competition for iron, many bacteria have multiple siderophores and uptake systems, thus trying to gain an edge on the other organisms in the same environment; some can efficiently extract iron from transferrin, an advantage at our expense. Other Functions of the Bacterial Membrane the cytoplasmic membrane of bacteria is also where cytochromes are located and oxidative metabolism is carried out. The membrane is also the location of nascent proteins destined either for secretion or incorporation in the membrane itself. Some bacteria secrete as much as 10% of all the proteins they make, including toxins and other virulence factors. The nascent peptide chains that have hydrophobic "signal sequences" at the N termini are translocated from ribosomes across the cytoplasmic membrane by an energyrequiring mechanism. Note that Gram-negative bacteria have the added problem of transporting proteins to the outer membrane. It follows that metronidazole and related drugs are particularly useful against anaerobic bacteria and against amoebas, which also grow anaerobically. To a small extent, the partial reduction to active agents occurs in normal tissue, leading to possible mutagenesis and perhaps carcinogenesis. The large requirement for proteins makes protein synthesis the principal biosynthetic activity of rapidly growing bacteria. Likewise, the rate of protein synthesis is proportional to the cellular concentration of ribosomes. Thus, the synthesis of the principal macromolecules of bacteria is regulated mainly by the frequency with which each chain is initiated and not so much by altering their rate of manufacture of each molecule. Antibiotics act selectively at initiation or elongation of macromolecular synthesis.
This skin lesion usually begins with bluish-red discoloration and swollen skin on an extremity gastritis diet авито quality 20 mg pantoprazole. Borrelia has been cultured from such lesions as much as 10 years after their onset chronic gastritis definition discount pantoprazole 20 mg without prescription. In rare cases syarat diet gastritis cheap 20mg pantoprazole with amex, however gastritis xq se produce cheap pantoprazole 20mg with visa, patients who have been diagnosed with Lyme disease and who have received the recommended course of antibiotics continue to suffer from symptoms such as fatigue, musculoskeletal pain, and loss of cognitive functions. In many patients, these manifestations represent a slow response to the antibiotic therapy, as patients report a gradual decrease in symptoms over time following treatment. Thus, prolonged antibiotic therapy is believed to be medically unjustified and in fact may expose patients to risks associated with any extended antibiotic treatment. It is usually difficult to visualize spirochetes in histologic sections due to the low number of spirochetes present even during an active infection. Instead, the diagnosis of Lyme disease is first and foremost a process of identifying clinical features, particularly erythema migrans, suggestive of Lyme disease coupled with a history that is compatible with exposure to infected deer ticks. After the first several weeks of infection, particularly if the spirochete disseminates, most patients become seropositive. However, even these serologic tests have their limitations, and interpretation requires some experience and skill. As early diagnosis of Lyme disease is critical to successful treatment, development of new antibody-based assays with enhanced sensitivity and reliability is an active area of Lyme disease research. The fact that the manifestations of Lyme disease are quite varied and not entirely specific has given rise to considerable dispute surrounding the diagnosis of Lyme disease. For example, the term "chronic Lyme disease" has been used by some to describe patients with persistent pain, neurocognitive symptoms, and fatigue but with no objective clinical or serological evidence of the patient ever having been infected with B. Thus, physicians have a responsibility to appropriately diagnose their patients using validated laboratory tests and clinical criteria and follow up with a suitable treatment regime. For stage 1 or 2, the duration of therapy is generally 2 to 4 weeks and is guided by the clinical presentation of illness. Patients with late stage Lyme disease, manifesting as arthritis, typically respond well to oral therapy with doxycycline or amoxicillin over a 4-week period. Except for syphilis, these are animal diseases that only incidentally affect humans when they are bitten by Borrelia-infected ticks or when they come in contact with animal urine contaminated with leptospires. All these spirochetes are highly motile, and all are capable of spreading from the initial site of infection. The initial phases of these infections have many similarities to Lyme disease, including the possible presence of fever, headache, muscle pain, meningitis, photophobia, malaise, or fatigue. Relapsing fever is associated with intermittent episodes of high fever, which are thought to occur because of variation of the major antigen, a surface protein of the spirochete. Leptospirosis often affects the kidney, but infection of many tissues is seen and can result in hemorrhage. Both Lyme disease and syphilis occur in stages over a period of years and typically cause neurologic abnormalities late in the illness. For syphilis and Lyme disease, diagnosis is usually made by recognition of a characteristic clinical picture with serologic confirmation. Mode of Transmission Ticks of the Ixodes ricinus complex Ornithodoros ticks, human body louse Sexual contact Contact with infected animals or their urine Characteristic Clinical Aspects Erythema migrans, recurrent arthritis Recurrent high fever Chancre, tabes dorsalis, aortitis Jaundice, renal involvement to four weeks of intravenous therapy is generally necessary for patients with objective neurologic involvement, such as Lyme meningitis, and the third-generation cephalosporin drugs. Once symptoms begin to improve, these patients can complete their treatment regime with oral antibiotics. In the Lyme disease field, researchers are actively examining a variety of novel vaccine approaches, including utilizing alternative B. Currently, the best advice for prevention is behavioral: people should be warned to minimize the chances of tick bites by wearing long pants tucked into socks, spraying clothing with insect repellent, and performing careful checks for feeding ticks daily when engaging in outdoor activities in Lyme-endemic areas, particularly in the spring and summer. As described above, removal of an Ixodes tick within the first 2 days of feeding is likely to prevent transmission of the spirochete. A Lyme vaccine based on OspA was available in the United States for several years. It has since been withdrawn from the market for various reasons, but provides interesting insight into B. As discussed earlier, OspA is expressed while the spirochete is in the tick midgut but is not usually expressed while the spirochete is in the mammalian host. Thus, anti-OspA antibody does not promote clearance of bacteria in the mammalian host. Instead, the anti-OspA antibody present in blood is ingested by the feeding tick and leads to killing of spirochetes in the tick midgut, thereby interrupting the activation and migration of spirochetes from the tick midgut to the salivary glands, a process required for mammalian infection. Untreated, the spirochete can cause a long-term, multisystemic illness that can be divided into three stages based on the site(s) and duration of infection. Because diagnosis is still largely dependent on clinical suspicion and evaluation of the patient rather than on laboratory tests, physicians and other health personnel must be alert to the possibility of this disease among people living in affected areas, especially those who are frequently outdoors. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.
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