Actinomycetes are a group of metabolically dynamic microorganisms. They are better known for the production of a wide range of antibiotics, anticancer drugs, and industrial enzymes. Only a small number of species belonging to the order Actinomycetales are pathogenic. From the evolutionary perspective, actinomycetes form a bridge between the classic bacteria and fungi. The properties that mandate their classification with bacteria include prokaryotic cell structure and in vitro sensitivity to most antibacterial antibiotics. On the other hand, their tendency to form true branching with septate mycelium, external spores, and granulomatous tissue reaction in infected hosts bring them closer to fungi. The term “actinomycete” literally means “ray fungus.” Because of their fungus-like properties, actinomycetes have been traditionally studied by mycologists. By early 1970s, it became obvious that these are prokaryotic microorganisms, and most mycologists started avoiding them, but bacteriologists did not quite embrace them either. As a result the study of actinomycetes has fallen into a “no man’s land.”
Actinomycetes are broadly divided into two major groups, the anaerobic acti-nomycetes and the aerobic actinomycetes. The anaerobic actinomycetes have only two medically important genera, Actinomyces and Rothia. The aerobic actinomycetes represent a much bigger group and include five genera of clinical significance that include species of Nocardia, Actinomadura, Streptomyces, Thermoactinomyces, and Saccharopolyspora. Aerobic actinomycetes that are commonly considered non-pathogenic include members of the genus Acinoplanes, Streptomyces (most species), Streptosporangium, Micromonospora, Micropolyspora, and several species of Nocardia and Actinomadura. Incidentally, the “nonpathogenic” aerobic actinomycetes are of immense industrial importance (see publications by Mishra et al. in the bibliography).
ANAEROBIC ACTINOMYCETES
Actinomyces Species
The genus Actinomyces includes anaerobic species that are typically Gram-positive. Infections caused by Actinomyces spp. are commonly referred to as actinomycosis, a disease that was quite common during the pre-antibiotics era. It seems, due to widespread use of antibiotics, that actinomycosis has been almost inadvertently eradicated from much of the world. The genus Actinomyces has two pathogenic species. Actinomyces israelii is a human pathogen that causes systemic or localized infection. The systemic infection may involve the lungs or even the brain. Localized infections are chronic in nature and frequently involve the gums or cheeks. The other species, A. bovis, causes lumpy jaw in the cattle.
Laboratory Diagnosis
Pus or sputum are inoculated into thioglycollate broth and incubated anaerobically for about 1 week at 35°C.
Antibiotic Sensitivity
Penicillin and a number of other commonly used antibiotics are quite effective in the treatment of actinomycosis.
Rothia dentocariosa
Rothia dentocariosa are commonly present in the human mouth, often below the gum line. They are anaerobic to facultative anaerobes, and are believed to play a role in the etiology of dental caries. Systemic, cutaneous, or subcutaneous infections are not known.
Nocardia Species
Unlike Actinomyces spp., Nocardia are aerobic bacteria and are commonly present in soil. Species of the genus Nocardia, especially N. asteroids and N. farcinica, and occasionally N. otitidiscaviarum (N. caviae) and N. brasiliensis, cause nocardiosis in humans. Nocardiosis is an airborne disease that primarily involves the lungs from where it may spread to other organs, especially to the brain for which it seems to have a predilection. Symptoms mimic tuberculosis and in fact in many parts of the world, nocardiosis is often referred to as Pseudotuberculosis. Symptoms may include cough, often accompanied by blood tinged sputum, and fever, which tends to be higher compared with tuberculosis. Like actinomycosis, cases of nocardiosis have greatly declined as compared with the pre-antibiotics era. However, in underdeveloped countries, it is quite possible that a significant number of tuberculosis patients actually suffer from nocardiosis.
Nocardia caviae and N. brasiliensis are better known for causing a clinically distinct condition called actinomycetoma, occasionally also referred to as “Madura foot.” It must be noted here that the term mycetoma refers to a localized chronic swelling that is also caused by fungi (therefore, the term “actinomycetoma” is used here). The disease mostly involves the foot and lower leg. In the later stage, the swellings start draining with pus containing “sulfur granule,” which is essentially a tight cluster of filaments surrounded by a large number of reactive cells, mostly neutrophils. Two other species that were previously classified as N. madurae and N. pelletieri, but are now called Actinomadura madurae and Actinomadura pelletieri, also cause actinomycetoma. No specific virulence factors have been identified except for the fact that a large number of aerobic actinomycetes produce toxins or antibiotic like substances. Some of the key physiological differences between clinically significant aerobic Actinomycetes are noted in Table 12.1.
Laboratory Diagnosis
Laboratory diagnosis of nocardiosis is not easy. Because the causal agents are sensitive to antibiotics, antibiotics cannot be incorporated in the isolation media. But the clinical specimens are often contaminated with fast-growing bacteria against which the slow-growing Nocardia cannot compete. In 1969, Mishra and Randhawa developed a selective technique called Paraffin Bait Technique for the isolation of pathogenic Nocardia spp. from heavily contaminated specimens. It depends on the ability of nocardiae to use paraffin as energy source (Fig. 12.1). Once isolated, Nocardia can be cultured on modified Sabouraud agar (2% glucose, 1% neopeptone, 2% agar, 1 L water). Relatively uncontaminated clinical specimens, such as biopsied tissue and CSF, can be directly cultured on modified Sabouraud agar. Strains of N. asteroides show remarkable differences in their appearance (Fig. 12.2), and readers are referred to the classic works of Mishra and Gordon (1980, 1981). Also, since several microorganisms including members of the genus Rhodococcus show a remarkable morphological similarity with pathogenic Nocardia spp., a number of physiological tests must be conducted for specific identification (see Table 12.1).
Antibiotic Sensitivity
Even though Nocardia spp. are quite sensitive to antibiotics in vitro, most strains do not respond favorably to most antibacterial antibiotics in vivo. The drug of choice for the treatment of nocardiosis is trimethoprim-sulfamethoxazole or carbapenems often supplemented with tetracycline.
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| Figure 12.1. Schematic demonstrating the use of the paraffin bait technique for the isolation of pathogenic Nocardia from sputum. See color insert |
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| Figure 12.2. Some differences in the appearance of the colonies of important aerobic actinomycetes: N. asteroides (left), N. brasiliensis (center), and Rhodococcus spp. (right). See color insert. |
Streptomyces Species
Streptomyces somaliensis is the only unequivocally recognized species that is known to cause infection in humans. Isolation of strains later identified as S. griseus and S. albus from clinical specimens has been occasionally reported, but their actual role in the causation of any disease is doubtful. Streptomyces somaliensis has been recognized as the causal agent of mycetoma or Madura foot in several cases. The clinical signs and symptoms resemble those of mycetoma caused by other aerobic actinomycetes. Most strains grow well on Sabouraud agar.
Thermoactinomyces Species and Saccharopolyspora Species
Thermophilic actinomycetes grow at a higher temperature, usually >45°C, and they are commonly present in the core of straw bales and piles of hay, where the temperature can be in excess of 45°C. The disease variously called farmer’s lung, allergic pneumonitis, or allergic alveolitis can be a life-threatening condition. It is essentially an allergic reaction, mediated by Type III reaction involving IgG and IgE antibodies. Cellular immunity also plays a role in the pathogenesis of this syndrome. Symptoms include pulmonary edema and breathing difficulties. The condition develops following repeated inhalation of the spores. Farmer’s lung accounts for >12% of cases of hypersensitivity pneumonitis in the United States with an incidence rate ranging from 8 to 500 cases per 100,000 persons per year. In Europe, especially in the United Kingdom, the incidence rate is reportedly 400–2,500 per 100,000 persons per year in the farming community. The disease is also noted in other European countries including France, Sweden, and Finland. The thermoactinomycetes commonly incriminated in Farmer’s lung include Thermoactinomyces vulgaris, T. sacchari, and Saccharopolyspora rectivirgula.
Laboratory Diagnosis and Control
The most dependable diagnostic test is the demonstration of specific precipitins in the immunodiffusion test. The patient’s clinical condition often correlates to how strong the precipitin bands are. Effective therapeutic measures include avoiding exposure to thermophilic actinomycetes and a judicious use of cortisone.
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