Co-Director, Southern California College of Osteopathic Medicine
In other Bacterial cells are not defenceless against genetic damage Since the bacterial genome is the most fundamental molecule of identity in the cell skin care arbonne buy genuine neotrex, enzymatic machinery is in place to protect it against both spontaneously occurring and induced Figure 2 acne 3 days generic 40mg neotrex overnight delivery. Thus acne jaw line buy neotrex without prescription, it is the least important mechanism of gene transfer from the standpoint of clinical relevance skin care 2020 purchase 20mg neotrex fast delivery. The study of these processes in bacteria has led to an important understanding of general principles that apply to higher organisms, including issues of cancer and aging in humans. In either case, this type of gene transfer is known as generalized transduction. As these prophages prepare to enter the lytic cycle, they occasionally incorrectly excise from the site of attachment. Gene transfer and recombination New genotypes arise when genetic material is transferred from one bacterium to another. Recombination can bring about large changes in the genetic material, and since these events usually involve functional genes, they are likely to be expressed phenotypically. Occasionally, conjugative plasmids such as the fertility plasmid (F plasmid or F factor) of E. However, conjugation with Hfr donor cells does not result in complete transfer of the integrated plasmid. Thus, the recipient cell does not become Hfr and is incapable of serving as a conjugation donor. When a non-conjugative plasmid is present in the same cell as a conjugative plasmid, they are sometimes transferred together into the recipient cell by a process known as mobilization. Conjugative transfer of plasmids with resistance genes has been an important cause of the spread of resistance to commonly used antibiotics within and between many bacterial species, since no recombination is required for expression in the recipient. Of all the mechanisms for gene transfer, this rapid and highly efficient movement of genetic information through bacterial populations is clearly of the highest clinical relevance. At present, the utilization of this information is in its infancy; nevertheless, several instances where sequence-based information will be extremely useful in the study of clinically important microorganisms have already emerged, as described below. Such information clearly has potential for future application in approaches to the rapid identification, classification and epidemiology of clinically important microorganisms (see Chs 31 and 36). However, total genome sequencing provides more detailed information to insure their detection and allows a global overview where multiple loci may interact to effect resistance. For example, methicillin resistance in Staphylococcus aureus is influenced by a number of genes. While a variety of phenotypic and genotypic methods have been employed to assess interrelationships in clinical isolates (see Ch. In contrast to earlier methods, sequence data are highly portable (internet transfer, etc. However, which chromosomal regions will ultimately provide the most epidemiologically relevant information in different bacterial pathogens will become clearer as additional genomes are sequenced. Nevertheless, the massive amounts of genomic sequence currently being generated have spawned innovative approaches aimed at extracting the maximum amount of information from the large databases which have been created. Regions encoding sequences helpful for species identification or epidemiology are indicated. While yielding important information, this approach is time consuming and does not afford ready access to the information (chromosomal organization and multiple-gene interaction) contained within genomic-sequence databases. Microarrays represent a new approach to this issue where information may be obtained from multiple queries simultaneously posed to a genomicsequence database (parallel processing). While there are a number of variations on the theme, the general format is the arrangement of samples. Different fluorescently labelled probes of known sequence may then be simultaneously applied followed by monitoring to detect whether complementary binding has occurred. Resistance to the quinolone class of antibiotics, for example, may result from a single base change within the bacterial gyrA gene (see Ch. Those appearing green will correspond to genes active in environment B, while yellow spots (red + green) will indicate genes active under both conditions. Two gyrA probes (wild type, fluorescently labelled red; mutant, fluorescently labelled green) are applied to the array under conditions so stringent that only 100% homology will result in hybridization. In this way, the presence or absence of the specific mutation may be quickly and accurately assessed in a large number of isolates simultaneously. Studies of gene expression are extremely important to the understanding of numerous bacterial processes, including virulence. For example, analysis might involve a comparison of gene expression (transcription) in an organism under different environmental conditions. In such an experiment, genomics can provide data allowing sequences from every known chromosomal gene of the organism to be applied to a unique position on the chip. Using the enzyme reverse transcriptase in a process similar to that naturally Major groups of bacteria Detailed summaries of members of the major bacterial groups are given in the Pathogen Parade appendix available online. A number produce highly resistant spores that can survive for long periods in the external world, increasing the chances of infection. For example, some hide within cells, some have external surfaces that prevent host cells binding to them, others suppress host immunity. Perhaps the most significant advantage bacteria have in their conflict with the host is their ability to sidestep the antibiotics designed to inhibit or eliminate them. A classic example of this interaction is seen with the Grampositive bacterium Staphylococcus aureus. Although initially susceptible to penicillin, introduced in the 1950s, subsequent development and spread of resistant organisms rendered the antibiotic ineffective.
Mechanisms to counteract mucus acne needle cheap neotrex 40mg overnight delivery, acids skin care vietnam neotrex 10mg overnight delivery, enzymes and bile Successful intestinal microbes must counteract or resist mucus skin care yang bagus dan murah discount neotrex online visa, acids acne rosacea order discount neotrex, enzymes and bile Mucus protects epithelial cells, perhaps acting as a mechanical barrier to infection. It may contain molecules that bind to microbial adhesins, therefore blocking attachment to host cells. It also contains microbe-specific secretory IgA antibodies, which protect the immune individual against infection. Microbial exotoxin, endotoxin and protein absorption Microbial exotoxins, endotoxins and proteins can be absorbed from the intestine on a small scale. The attached bacteria induce apoptosis in gastric epithelial cells, as well as inflammation, dyspepsia and occasionally a duodenal or gastric ulcer, so that treatment of these ulcers is by antibiotics rather than merely antacids. The bacteria do not invade tissues, and they stay in the stomach for years, causing asymptomatic chronic gastritis. Up to 3% of infected individuals develop chronic active gastritis and progress to intestinal metaplasia which can lead to stomach cancer. How to survive stomach acid: the neutralization strategy of Helicobacter pylori this bacterium was discovered in 1983, and was shown to be a human pathogen when two courageous doctors, Warren and Marshall in Perth, Western Australia, drank a potion containing the bacteria and developed gastritis. Today, in countries with improved hygiene, this is put off until later in life, until at the age of 50 more than half of the population have been infected. After being eaten, the bacteria have a number of strategies resulting in adaptation to the host gastric mucosa having attached by special adhesins to the stomach wall. These include host mimicry leading to evasion protein also takes place more readily in the infant, which in some species needs to absorb antibodies from milk. As well as large molecules, particles the size of viruses can also be taken up from the intestinal lumen. M cells take up particles and foreign proteins and deliver them to underlying immune cells with which they are intimately associated by cytoplasmic processes. If other microorganisms are to colonize and invade they must either have specific mechanisms for attaching to vaginal or cervical mucosa or take advantage of minute local injuries during coitus (genital warts, syphilis) or impaired defences (presence of tampons, estrogen imbalance). Urethral and bladder defences the regular flushing action of urine is a major urethral defence, and urine in the bladder is normally sterile. The bladder is more than an inert receptacle, and in its wall there are intrinsic, but poorly understood, defence mechanisms. These include a protective layer of mucus and the ability to generate inflammatory responses and produce secretory antibodies and immune cells. Urogenital tract Microorganisms gaining entry via the urogenital tract can spread easily from one part of the tract to another the urogenital tract is a continuum, so microorganisms can spread easily from one part to another, and the distinction between vaginitis and urethritis, or between urethritis and cystitis, is not always easy or necessary (see Chs 20 and 21). Mechanism of urinary tract invasion the urinary tract is nearly always invaded from the exterior via the urethra, and an invading microorganism must first and foremost avoid being washed out during urination. Specialized attachment mechanisms have therefore been developed by successful invaders. A defined peptide on the bacterial pili binds to a syndecan-like proteoglycan on the urethral cell, and the cell is then induced to engulf the bacterium. This is referred to as parasite-directed endocytosis and also occurs with chlamydia. This is because sexually transmitted pathogens often remain in the moist area beneath the foreskin after detumescence, giving them increased opportunity to invade. Spread to the bladder is no easy task in the male, where the flaccid Vaginal defences the vagina has no particular cleansing mechanisms, and repeated introductions of a contaminated, sometimes pathogen-bearing foreign object (the penis), makes the vagina particularly vulnerable to infection, forming the basis for sexually transmitted diseases (see Ch. During reproductive life, the vaginal epithelium contains glycogen due to the action of circulating estrogens, and certain lactobacilli colonize the vagina, metabolizing the glycogen to produce lactic acid. The invading bacteria often begin their invasion by colonizing the mucosa around the urethra and probably have special attachment mechanisms to cells in this area. Bacterial invasion is favoured by the mechanical deformation of the urethra and surrounding region that occurs during sexual intercourse, which can lead to urethritis and cystitis. Oropharynx Microorganisms can invade the oropharynx when mucosal resistance is reduced Commensal microorganisms in the oropharynx are described in Chapter 18. On the other hand, material borne backwards from the nasopharynx is firmly wiped against the pharynx by the tongue during swallowing, and microbes therefore have an opportunity to enter the body at this site. Additional defences include secretory IgA antibodies, antimicrobial substances such as lysozyme, the normal flora, and the antimicrobial activities of leukocytes present on mucosal surfaces and in saliva. Attaching to mucosal or tooth surfaces is obligatory for both invading and resident microorganisms. For instance, different types of streptococci make specific attachments via lipoteichoic acid molecules on their pili to the buccal epithelium and tongue (resident Streptococcus salivarius), to teeth (resident Strep. Factors that reduce mucosal resistance allow commensal and other bacteria to invade, as in the cases of gum infections caused by vitamin C deficiency, or of Candida invasion (thrush) promoted by changed resident flora after broad-spectrum antibiotics. In dehydrated patients, salivary flow is greatly reduced and the mouth soon becomes overgrown with bacteria. As at all body surfaces, there is a shifting boundary between good behaviour by residents and tissue invasion according to changes in host defences. Therefore, urinary infections are rare in males unless organisms are introduced by catheters or when the flushing activity of urine is impaired (see Ch.
These early defence mechanisms occur more rapidly but are less specific than the adaptive mechanisms based on lymphocyte (T and B cell) responses skin care usa order neotrex no prescription. Together skin care coconut oil 10 mg neotrex, these act as a first line of defence during the initial hours or days of infection acne drugs discount 40mg neotrex free shipping. Sometimes acne guidelines purchase neotrex pills in toronto, as in the common viral infections, cellmediated immunity is responsible for recovery from infection, and antibody for the maintenance of immunity. Failure to recover from infection may be due to some deficiency of host immunity or to successful evasion strategies used by the microorganism. Local spread takes place readily on a fluid-covered mucosal surface, often aided by ciliary action, and large-scale movements of fluid spread the infection to more distant areas on the surface. As a result, large areas of the body surface can be involved within a few days, with shedding to the exterior. In contrast, other microorganisms spread systemically through the body via lymph or blood. They often undergo a complex or stepwise invasion of various tissues before reaching the final site of replication and shedding to the exterior. The microbe must reach the replication site, and there is then no need for extensive replication at the site of initial infection. For instance, mumps and hepatitis A viruses infect via the respiratory and alimentary routes, respectively, but must spread through the body to invade and multiply in salivary glands (mumps) and liver (hepatitis A). Why do the microbes that cause systemic infections leave the relatively safe haven of the body surface to spread through the body, where they will bear the full onslaught of host defences For instance, what are the factors that persuade meningococci residing harmlessly on the nasal mucosa to invade deeper tissues, reach the blood and meninges, and cause meningitis (see Ch. Mycobacterium leprae is also temperature sensitive, which accounts for its replication being more or less limited to nasal mucosa, skin and superficial nerves. Influenza and parainfluenza viruses invade surface epithelial cells of the lung, but are liberated by budding from the free (external) surface of the epithelial cell, not from the basal layer from where they could spread to deeper tissues. Many microorganisms are obliged to spread systemically because they fail to spread and multiply at the site of initial infection, the body surface. In the case of measles or typhoid, there is, for unknown reasons, next to no replication at the site of initial respiratory or intestinal infection. Only after spreading through the body systemically are large numbers of microorganisms delivered back to the same surfaces, where they multiply and are shed to the exterior. Other microorganisms need to spread systemically because they have committed themselves to infection by one route, while major replication and shedding occurs In systemic infections, there is a stepwise invasion of different tissues of the body this stepwise invasion is illustrated in Figure 15. Although the final sites of multiplication may be essential for microbial shedding and transmission. Bone marrow and muscle are possible sources for secondary parasitaemia in addition to blood vessels, liver and spleen. In dengue, malaria and typhus, multiplication occurs in blood cells or vascular endothelium. Poliovirus invades the brain and spinal cord from the blood, but is not shed from these sites, whereas rabies invades and later travels from brain to salivary glands via peripheral nerves. Mycobacterium tuberculosis) is likely to cause a slowly evolving disease with a long incubation period. Microorganisms nearly always multiply faster in vitro than they do in the intact host, as might be expected if host defences are performing a useful function. In the host, microorganisms are phagocytosed and killed and the supply of nutrients may be limited. The net increase in numbers is slower than in laboratory cultures where microbes are not only free from attack by host defences, but also every effort has been made to supply them with optimal nutrients, susceptible cells, and so on. Local tissues consist of various cells in a hydrated gel matrix; although viruses can spread by stepwise invasion of cells, invasion is more difficult for bacteria, and those that spread effectively sometimes possess special spreading factors. The rich network of the lymphatic system soon conveys microorganisms to the battery of phagocytic and immunologic defences awaiting them in the local lymph node. Macrophages, strategically placed in the marginal and other lymph sinuses, constitute an efficient filtering system for lymph. Escherichia coli, staphylococci Salmonella typhimurium Mycobacterium tuberculosis Mycobacterium lepraeb Treponema pallidum b In cella In vitro Figure 15. These microbes are not shed to the exterior after multiplying in the meninges or spinal cord. For the microbe, systemic spread is fraught with obstacles, and a major encounter with immune and other defences is inevitable. Microorganisms have therefore been forced to develop strategies for bypassing or countering these defences (see Ch. Hit-and-run (surface) infections need to replicate rapidly, whereas a microorganism that divides a But some viruses show greatly delayed replication or delayed spread from cell to cell. Microbes (or other particles) beneath surface epithelium readily enter local lymphatics. The infection may be halted at any stage, but by multiplying locally or in lymph nodes and by evading phagocytosis, the microorganism can ultimately reach the bloodstream. Therefore, a minor injury to the skin, followed by a red streak (inflamed lymphatic) and a tender, swollen local lymph node are classic signs of streptococcal invasion. In the early stages, lymph flow increases, but eventually, if there is enough inflammation and tissue damage in the node itself, the flow of the lymph may cease. In contrast, viruses and other intracellular microorganisms often invade lymph and blood silently and asymptomatically during the incubation period; this is facilitated when they infect monocytes or lymphocytes without initially damaging them.
Perfectly healthy individuals are susceptible skin care salon order neotrex with visa, and most of these viruses have surface molecules that attach specifically to the respiratory epithelium skin care quotes generic 20 mg neotrex mastercard. Even when viruses of this group do not themselves cause pneumonia acne problems order neotrex once a day, they may damage respiratory defences acne on arms purchase 40 mg neotrex otc, laying the ground for secondary bacterial pneumonia. Sometimes the virus fails to spread significantly to air spaces, but remains in interstitial tissues to cause interstitial pneumonitis. Pneumonia is treated with appropriate antimicrobial therapy Once the cause of the pneumonia has been identified, selection of the appropriate antimicrobial therapy is relatively straightforward (Table 19. The choice of treatment is more difficult when sputum is not produced or does not reveal the pathogen. It is therefore important to take a full history and use invasive diagnostic techniques if appropriate to help establish the cause. It is always better to demonstrate a rising titre between acute- and convalescent-phase sera than to rely on a single sample. Penicillin-resistant pneumococci now occur in many countries, and in some it is no longer safe to assume susceptibility to penicillin (or ampicillin). Many of the resistant strains are still susceptible to cephalosporins, and in countries with a high incidence of resistance, these agents may replace penicillin, at least until the results of antibiotic susceptibility are known. It is important to recognize that penicillin (and ampicillin and cephalosporins) is not active against the other common causes of pneumonia. Some, such as influenza and measles, leave the patient particularly susceptible to secondary bacterial infection. There are four types of parainfluenza viruses with differing clinical effects the surface spikes of parainfluenza viruses are composed of haemagglutinin plus neuraminidase on one type of spike and fusion proteins on another. After infection by respiratory droplets, these viruses spread locally on respiratory epithelium. Croup is seen in children less than 5 years of age, and consists of acute laryngotracheobronchitis with a harsh cough and hoarseness. Parainfluenza virus 4 is less common and generally causes a common-cold-type illness. Virus-specific antigens can be detected in cells from respiratory washings, and virus culture can be carried out, in settings where molecular analysis is not available. Ribavirin may be given in severe infections or in immunosuppressed individuals but there is no vaccine. Adenovirus respiratory tract infections generally cause non-specific symptoms in children less than 5 years of age. As maternal antibody wanes, lower respiratory tract illnesses become more frequent, especially with adenovirus 7. Types 3, 4 and 7 have caused outbreaks of respiratory illness ranging from pharyngitis to atypical pneumonia in military recruits, with crowding and stress as possible co-factors. Recovery is generally uneventful, but adenoviruses may persist in the body, because they can be recovered from at least 50% of surgically removed tonsils. An enteric-coated vaccine for types 4 and 7 has been used to prevent outbreaks of infection in military recruits. The influenza virus envelope has haemagglutinin and neuraminidase spikes these are shown in Figure 19. In the case of influenza A, the haemagglutinin (H) and neuraminidase (N) are typespecific antigens and are used to characterize different strains of influenza A virus (Table 19. In giving the full nomenclature, the influenza type, the location and year of isolation is also included. It is associated with a spectrum of illness from mild infection to bronchiolitis and pneumonia. Influenza viruses undergo genetic change as they spread through the host species these changes are of two types: 1. When changes in these antigens enable the virus to multiply significantly in individuals with immunity to preceding strains, the new subtype can reinfect the community. Less commonly, and only with influenza A, there is a sudden major change referred to as shift, in the antigenicity of the H or N antigens. This is based on recombination between different virus strains when they infect the same cell. The major change in H or N means that the new strain can spread through populations immune to pre-existing strains and the stage is set for a new pandemic (Table 19. Associated with the change in H and N are other genetic changes, which may or may not confer increased pathogenicity or change the ability to spread rapidly from person to person. A report from Sweden compared the results of testing 258 children with lower respiratory tract infections with, and 282 without, a diagnosis. The virus has been detected in faecal and serum samples and as a coinfection in respiratory samples. It was so named after an outbreak of a respiratory disease in Italy in the fifteenth century that was thought to have developed under the influence of the stars. The mixing vessel hypothesis for the production of new influenza strains came about as a result of influenza A viruses infecting pigs, horses, seals and other mammals, and the ability of the virus to reassort. For example, pigs in some countries live in the same dwellings as the farmers, allowing the potential mixing of influenza viruses and emergence of new strains. These were examples of antigenic shift, whereas antigenic drift resulted in frequent epidemics between the pandemic years. The outbreak ceased after public health authorities ordered the slaughter of all live chickens in Hong Kong. Five human infections were reported in 1999 in Hong Kong and South China with the avian influenza A virus, H9N2.
