The Genera Mycoplasma and Ureaplasma

Chapter 39 The Genera Mycoplasma and Ureaplasma


Mycoplasmas and ureaplasmas, members of the family Mycoplasmataceae, arethe smallest prokaryotes and are related phylogenetically to members of the genera Clostridium, Streptococcus, and Lactobacillus. Members are distinct from other bacteria in their small genome size (0.58-1.35 Mb, which accounts for their limited metabolic options for replication and survival), and lack of cell wall synthesis (which places them in the class Mollicutes [soft skin] and renders them resistant to antimicrobials that interfere with cell wall synthesis). Mollicutes are of gram-positive lineage, but absence of a cell wall makes them unable to retain crystal violet/Gram’s iodine, so Gram staining is not part of the identification process.


Mycoplasmas and ureaplasmas have complex nutritional requirements because of their limited biosynthetic capabilities, and depend in vivoon the host microenvironment. Most genes for amino acid and cofactor biosynthesis werelost during evolution. Exogenous fatty acids and sterols are required; the latter separates the family Mycoplasmataceae from similar organisms and is useful in their identification because it renders them sensitive to digitonin.


This group of organisms is widely distributed in humans, mammals, birds, reptiles, fish, and plants, and requires intimate association with host cell surfaces for growth. Until recently, these agents were considered to be strict pathogens of the mucous membranes, associated mainly with respiratory, arthritic, or genitourinary tract diseases. That dogma has changed with recognition of a new group, the hemotrophic mycoplasmas or hemoplasmas, which parasitize erythrocytes and are refractory to cultivation on solid media.



THE GENUS MYCOPLASMA


The genus Mycoplasma comprises more than100 species, some of which cause chronic diseases in animals and humans. The majority of mycoplasmas have species-specific host-organism associations or tropisms for particular anatomic sites. The lack of a cell wall accounts for their plasticity and allows them to pass through filters with pore sizes as small as 450 nm, despite cell diameters ranging from 0.3 to 0.8 μm. Mycoplasmas are structurally simple, in that they consist ofribosomes and DNA bound by a trilaminar cytoplasmic membrane composed of sterols, phospholipids, and proteins. Most are facultatively anaerobic, except for the human pathogen Mycoplasma pneumoniae, which is a strict aerobe. They grow slowly, with a generation time of 1 to6 hours.



Diseases and Epidemiology


Mycoplasma spp. infect a variety of animals, and some of diseases attributed to them have major economic impacts (Table 39-1). As a general rule, infections are spread among susceptible individuals through direct or droplet contact with oral, nasal, ocular, or genital secretions. Mycoplasmas are typically introduced into a group by the addition of clinically healthy carrier animals.


TABLE 39-1 Mycoplasma Species That Infect Domestic Animals

























































































Species Host(s)
M. agalactiae Goats, sheep: contagious agalactia
M. alkalescens Cattle: arthritis, mastitis
M. bovigenitalium Cattle: infertility, mastitis
M. bovis Cattle: arthritis, mastitis, pneumonia, abortions, abscesses, otitis media, genital infections
M. bovoculi Cattle: conjunctivitis
M. californicum Cattle: mastitis
M. canadense Cattle: abortions, mastitis
M. capricolum ssp. capricolum Goats, sheep: mastitis, septicemia, polyarthritis, pneumonia
M. capricolum ssp. capripneumoniae Goats: contagious caprine pleuropneumonia
M. conjunctivae Sheep, goats: infectious keratoconjunctivitis
M. cynos Dogs: pneumonia
M. dispar Cattle: bronchiolitis
M. equigenitalium Horses: abortion?
M. felis Cats: conjunctivitis, pneumonia
Horses: pneumonia
M. gallisepticum Chickens, turkeys: airsacculitis, sinusitis
M. gatae Cats: chronic arthritis, tenosynovitis
M. hyopneumoniae Pigs: enzootic pneumonia
M. hyorhinis Pigs: polyarthritis, polyserositis
M. hyosynoviae Pigs: polyarthritis
M. iowae Turkeys: embryo mortality
M. meleagridis Turkeys: airsacculitis, skeletal abnormalities, decreased growth
M. mycoides ssp. capri Goats: arthritis, mastitis, pleuropneumonia, septicemia
M. mycoides ssp. mycoides (small-colony type) Cattle, domestic water buffalo: contagious bovine pleuropneumonia
M. mycoides ssp. mycoides (large-colony type) Goats, sheep: mastitis, septicemia, polyarthritis, pneumonia
M. ovipneumoniae Goats, sheep: pleuropneumonia
M. pulmonis Laboratory rats and mice: murine respiratory mycoplasmosis
M. synoviae Chickens, turkeys: infectious synovitis

In poultry, the predominant mycoplas-mal pathogens are Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma meleagridis, and Mycoplasma iowae. Mycoplasma gallisepticum infection commonly results in chronic respiratory disease in chickens. Clinical signs include nasal discharge, coughing, sneezing, tracheal rales, and conjunctivitis. Turkeys are more susceptible than chickens and often develop severe sinusi-tis (Figure 39-1). Other less common diseasesyndromes are keratoconjunctivitis, arthritis, salpingitis, and encephalopathy. Mycoplasma synoviae usually causes a subclinical upper respiratory infection but may result in airsacculitis and synovitis in chickens and turkeys. Some strains of M. synoviae produce subclinical infection, a characteristic that creates difficulty in the management and control of disease outbreaks. Infectionsmay result in financial loss to the industry through processing condemnations, as well as reduced growth efficiency and egg production. Mycoplasma meleagridis causes respiratory disease in young turkeys and is involved in stunting, poor feathering, and leg problems. Mycoplasma iowae infection is economically important in turkeys, and the organism has occasionally been isolated from chickens. In turkeys it has been associated with reduced hatchability and embryo mortality, whereas experimentally infected chickens and turkeys develop airsacculitis and leg abnormalities. Avian mycoplasmas are egg transmitted and may spread laterally by direct or indirect contact. The mode of transmission of M. meleagridis to the egg is venereal. Infection of the male thallus results in semen contamination, which leads to oviduct infection after mating. With all of the avian pathogenic mycoplasmas, disease severity is dependent on the virulence of the strain involved, the age and breed of the bird, the degree of stress, methods of management, and presence of concurrent bacterial or viral infections.



Three species of mycoplasmas commonly causing disease in swine are Mycoplasma hyopneumoniae, Mycoplasma hyosynoviae, and Mycoplasma hyorhinis. Mycoplasma hyopneumoniae is recognized as the etiologic agent of porcine enzootic pneumonia, which is characterized by high morbidity and low mortality that is commonly complicated by other opportunistic bacterial or viral infections. Enzootic pneumonia is an important economic problem affecting swine production worldwide. Clinical pneumonia is common in young animals but generally not seen in adults. Mycoplasma hyopneumoniae is transmitted from older to younger pigs by contact. Mechanical transmission by man and other animals is possible, and the organism may spread on the wind for several miles. Surveys conducted in different countries have revealed lesions of enzootic pneumonia in 30% to 80% of slaughter pigs. Feed conversion may be reduced by 14% to 20% and rate of gain by 16% to 30% in affected swine. The primary clinical sign is a sporadic dry nonproductive cough. Other signs may include fever, dyspnea, or impaired growth. Typical lesions are located in the apical and cardiac lobes of the lung, andconsist of well-demarcated, dark red to purple areas in acute disease, or tan to gray areas in chronic disease. Microscopic examination reveals characteristic lesions that include suppurative bronchopneumonia, histiocytic alveolitis with peribronchiolar and perivascular lymphohistiocytic cuffing, and nodule formation typical of bronchoalveolar lymphoid hyperplasia (Figure 39-2).



Mycoplasma hyosynoviae is a common inhabitant of the upper respiratory tract that may occasionally be recovered from 3- to 6-month-old pigs with polyarthritis. Disease is sporadic and of low morbidity. Mycoplasma hyorhinis is a sporadic cause of polyserositis and polyarthritis, which is indistinguishable from Glasser’s disease in pigs less than3 months old. Infections are also sporadic in nature.


More than 20 species of Mycoplasma have been recovered from cattle. Many are purely commensal in nature, whereas others are responsible for a wide variety of clinical manifestations. Mycoplasma mycoides ssp. mycoides, isolated in 1898, was the first Mycoplasma species associated with animal disease. The small colony variant is the causative agent of contagious bovine pleuropneumonia (CBPP), one of the most important cattle diseases in history. The first veterinary college was founded to train practitioners to deal with CBPP. The disease has been eradicated from North America, Europe, and Australia, but remains endemic in parts of Africa and Asia. The disease is characterized by marked edema of the interlobular septa, with diffuse pneumonia and serofibrinous pleuritis (Figure 39-3). Infection spreads slowly within a herd, and may reach a peak morbidity rate of 50% only after several months. The disease may have acute or chronic manifestations.



Mycoplasma bovis is among the most virulent mycoplasmas of cattle worldwide. It is most often associated with bronchopneumonia, and infection is believed to be a predisposing factor inthe development of bovine respiratory disease complex, or shipping fever. Mycoplasma bovis is capable of systemic invasion, and arthritis and meningitis may be sequelae to mycoplasmemia. In addition, M. bovis has been associated with otitis media, mastitis, keratoconjunctivitis, endometritis, oophoritis, abortion, and seminal vesiculitis. In the United States alone, costs in the form of decreased weight gains and loss of production have been estimated at $32 million per year.


It is not clear whether mycoplasmas are primary pathogens or opportunistic invaders in cats and dogs. Results of one survey indicated that mycoplasmas are part of the oropharyngeal flora in 33% of cats; however, they are not normal inhabitantsof the lower respiratory tract. Sporadic reports of mycoplasmal pneumonia, bronchial disease, bite wound abscesses, and pyothorax have been described. Mycoplasma felis is a significantetiologic agent of conjunctivitis in young cats, as well as a secondary invader in pneumonia. Mycoplasmas have been isolated from the upper respiratory tract of 25% of healthy dogs andfrom 21% of animals with pulmonary disease. Mycoplasma cynos is frequently recovered from chronic pulmonary mycoplasmosis in dogs. Mycoplasmas have been implicated as agents of canine infertility, but several studies have found no difference in mycoplasma recovery rates from the vagina or semen of fertile versus infertile dogs. There are several reports of endometritis associated with Mycoplasma canis.


Many mycoplasmas have been isolated from sheep and goats, but few are considered tobe pathogens, and these are associated withpneumonia, mastitis, arthritis, genital infections, and conjunctivitis. The two most important diseases of small ruminants are contagious caprine pleuropneumonia and contagious agalactia. These are responsible for major losses in goat herds in Africa and Asia and are designated list B diseases by the Office International des Epizooties. Mycoplasma capricolum ssp. capripneumoniae is the primary etiologic agent of caprine pleuropneumonia, a severe disease that may result in 100% morbidity and 80% mortality upon initial exposure of animals in naive herds. Contagious agalactia caused by Mycoplasma agalactiae has been estimated to cause annual losses in excess of$30 million in European countries, mainly as a result of decreased milk production. Severe mastitis and a decline in milk production are the first clinical signs of this primarily lactational disease. It may progress to septicemia and death in 20% of affected animals, and keratoconjunctivitis and arthritis are common sequelae in survivors. The udder may undergo complete fibrosis, resulting in permanent agalactia. Young ruminants become infected as a result of suckling, which may result in arthritis.


Of the 10 Mycoplasma species recovered from horses, only M. felis is considered pathogenic. It is a demonstrated cause of pleuritis. Mycoplasmas have been isolated from equine fetuses, but their etiologic role has not been established. Other species are apparent commensals of the upper respiratory and lower genitourinary tracts.



Pathogenesis


Mycoplasmas have evolved unique strategies that allow them to survive and replicate in hosts. Some of their inherent properties may cause damage to host cells; their inability to synthesize many essential nutrients forces them into competition with host cells, altering cellular integrity and function. For example, nonfermenting mycoplasmas use the arginine dihydrolase pathway to generate ATP, and host cell protein synthesis grinds to a halt when arginine reserves are depleted.


Cytadhesins are among the major virulence determinants of mycoplasmas. One such is the P97 protein of M. hyopneumoniae. The organism attaches to cilia of respiratory epithelial cells, resulting in damage to and subsequent loss of cilia (Figure 39-4). Lung damage results, as the lungs become predisposed to infection by secondary bacteria and the effects of other irritants. Cytadhesins have also been identified in M. gallisepticum, M. synoviae, and the human pathogen, M. pneumoniae.



Intimate association of mycoplasmas with the host cellular surface may lead to a buildup in the local concentration of cytotoxic metabolites and cytolytic enzymes. Hydrogen peroxide production is thought to play a role in the pathogenicity of some mycoplasmas, including M. pneumoniae and Mycoplasma dispar. Its production may induce oxidative stress in host cells, resulting in damage to the cellular membrane. Many Mycoplasma species have membrane-bound phospholipases that may release cytolytic lysophospholipids capable of disrupting host cell membranes.


Mycoplasmas produce at least three different types of modulins (molecular moieties that induce cytokine synthesis with pathologic consequences). Mycoplasmal lipoproteins play a key role in pathogenesis, stimulating monocytes and inducing secretion of proinflammatory cytokines and interleukins. The resulting pulmonary inflammation is characteristic of mycoplasma pneumonia. Infections are further characterized by initial infiltration of neutrophils, followed by an influx of macrophages and lymphocytes. The extent of neutrophil infiltration is directly correlated with disease severity because neutrophil attraction is controlled by chemotactic cytokines. Several mycoplasmas (M. pneumoniae and Mycoplasma arthritidis) function as superantigens, stimulating migration of inflammatory cells to infection sites, with subsequent release of cytokines. Certain mycoplasmas also can modulate immune functions, including induction of bovine lymphocyte apoptosis by M. bovis.


An important characteristic of mycoplasma infections is chronicity, and this may be basedin immune evasion. Antigenic variation may beutilized by mycoplasmas, including M. bovis, Mycoplasma pulmonis, and M. gallisepticum, to evade the immune response and cause chronic infection. Mycoplasmas have the genetic capability to alter, at high frequency, the structure and expression of membrane lipoproteins that are exposedto the host immune system. The exact mechanism underlying lipoprotein variation is not precisely understood.


Another virulence factor, which may be important in infections by M. mycoides ssp. mycoides and M. dispar, is a polysaccharide capsule, which may afford protection from phagocytosis.


Mycoplasma infection predisposes to infection with other pathogens, and mycoplasmas can act synergistically with these pathogens to increase disease severity. Studies indicate that M. hyopneumoniae potentiates pneumonia induced by porcine respiratory and reproductive syndrome virus. Mycoplasmas appear to play a role in accelerating the progression of human immunodeficiency virus infection to acquired immunodeficiency syndrome (AIDS).

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on The Genera Mycoplasma and Ureaplasma

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