Mycoplasma spp. Infections

Mycoplasmae are pleomorphic organisms that lack a cell wall and are enclosed by a single limiting membrane. Despite their lack of a cell wall, they are genetically related to several Gram-positive bacteria (Streptococcus, Lactobacillus, Clostridium, etc.).

Respiratory and Genital Mycoplasmosis

Laboratory mice are host to several Mycoplasma species within the pneumoniae group, including M. pulmonis, M. arthritidis, M. neurolyticum, M. collis, and M. muris. An unclassified Mycoplasma, the “gray lung” agent, appears to be distantly related to M. pulmonis (84% homology) and more closely related to M. hominis (94% homology). The name M. ravipulmonis (ravi, gray; pulmonis, lung) has been proposed. Mycoplasma pulmonis, M. arthritidis, and M. neurolyticum inhabit the upper respiratory tract, and M. collis and M. muris inhabit the genital tract. Only M. pulmonis is a significant natural pathogen that pro­duces respiratory and genital tract disease in mice and rats. Mycoplasma arthritidis may cause respiratory disease following intranasal inoculation, but under natural con­ditions, it is generally nonpathogenic. It is problematic primarily because it can cause seroconversion to M.

Epizootiology and Pathogenesis

Prior to and during the 1960s, infections with M. pulmo­nis were widespread among colonies of laboratory mice. With improvements in management practices, there has been a marked reduction in the prevalence of infected colonies of mice. Exposure occurs by aerosol transmis­sion, but infection may also be venereally transmitted. Newborn animals become infected during the first few weeks of life from contact with infected mothers. Trans­placental transmission can occur in rats and is likely, but not documented, in immunodeficient mice with dissem­inated infections. Mycoplasma has the potential of being transmitted through cesarean transfer, embryo transfer, or in vitro fertilization.

Compared with the laboratory rat, mice are relatively resistant to disease, and experimental disease severity is closely linked to inoculum dose. Susceptibility to disease depends upon the strain or isolate of M. pulmonis, but also on the genetic strain of mouse. Genetic resistance is complex and does not appear to be H-2 linked. C57BR, B6, and B10 mice are resistant, whereas C57L, SJL, BALB, A/J, C3H/HeJ, C3H/HeN, C3HeB, SWR, AKR, CBA/N, C58, and DBA/2 mice have been shown to be variably susceptible. Most experimental studies have compared disease between susceptible C3H and resistant B6 mice, and female mice have been found to develop more severe disease.

Mycoplasma pulmonis colonizes the apical cell mem­branes of respiratory epithelium and interferes with mucociliary clearance. Mycoplasmosis is exacerbated by viral infections, particularly Sendai virus, by other bacteria, including Pasteurella pneumotropica, and by environmental ammonia levels. These cofactors proba­bly play a significant role in driving subclinical myco­plasmal infections into overt disease. Mycoplasma pulmonis is mitogenic for B cells, which contributes to the pathology (peribronchiolar lymphoplasmacytic infiltrates) observed in the lungs. CAR bacillus has simi­lar mechanisms of altered mucociliary clearance and B-cell mitogenesis, thereby causing similar disease. Coinfection with CAR bacillus in cases of mycoplasmosis is common. The acquired immune response is important in limiting hematogenous dissemination of the infec­tion, but contributes little to elimination of infection or resolution of disease (for additional information, see Rat Chapter 2, “M. pulmonis infection”).

Pathology

Infection is often subclinical or mild in mice. In natural outbreaks of disease, affected mice may exhibit weight loss, dyspnea, and a characteristic “chattering” sound. Mice with otitis may display head tilt, circling, or ves­tibular signs. Mucopurulent exudate may be present in the nasal passages, tympanic bullae, trachea, and major airways. In advanced cases, anteroventral gray-purple areas of atelectasis, bronchiolectasis, broncho­pneumonia, and raised yellow-tan nodules with absces­sation may be evident on gross examination (Fig.

Although more common in the rat, chronic suppu­rative oophoritis, perioophoritis, salpingitis, and

FIG. 1.68. Lungs from a mouse with respiratory mycoplasmosis. Note the multiple pale raised bronchiolectatic lesions.

FIG. 1.69. Larynx from a mouse with chronic Mycoplasma pulmonis infection. Multinucleated giant cells are present in the respiratory epithelium. This is a common feature of the disease in this species that is not seen in rats.

endometritis are readily induced experimentally in mice and have been reported to occur in naturally infected mice. Isolation from the vagina and uterus of naturally infected mice and mice in contact with experimentally infected mice has also been docu­mented.

FIG. 1.70. Bilateral chronic suppurative otitis media due to Mycoplasma pulmonis infection. Note the presence of exudate in the opened tympanic bullae.

Diagnosis

Gross and microscopic lesions are characteristic. Histo­logical assessment should include a search for syncytia in the upper respiratory tract, a characteristic of mycoplas­mosis in mice. Staining procedures such as the Warthin- Starry method should be performed on tissue sections of major airways to determine if there is coinfection with CAR bacillus. Serology, based upon whole bacterial lysate antigen, is widely used for detecting infection in mouse populations. Some infected mice, such as B6 mice or young mice, may have relatively low antibody titers to M. pulmonis, and seroconversion to M. pulmonis may occur in mice infected with M. arthritidis. For culture, nasopharyngeal flushing and tracheobronchial lavages with Mycoplasma broth or phosphate-buffered saline are recommended procedures, but cultures are often negative in affected animals and have been supplanted by PCR assays. The respiratory tract should also be cultured for bacteria such as P. pneumotropica and serum should be tested for antibody to other respiratory pathogens. Differ­ential diagnoses include bronchopneumonia associated with CAR bacillus, as well as primary infections with Sendai virus and secondary bacterial infections. Otitis media and genital tract inflammation can be caused by a variety of other opportunistic bacteria.