The recent explosion of newly described species of Nocardia results from the impact in the last decade of newer molecular technology, including PCR restriction enzyme analysis and 16S rRNA sequencing. These molecular techniques have revolutionized the identification of the nocardiae by providing rapid and accurate identification of recognized nocardiae and, at the same time, revealing new species and a number of yet-to-be-described species. There are currently more than 30 species of nocardiae of human clinical significance, with the majority of isolates being N. nova complex, N. abscessus, N. transvalensis complex, N. farcinica, N. asteroides type VI (N. cyriacigeorgica), and N. brasiliensis. These species cause a wide variety of diseases and have variable drug susceptibilities. Accurate identification often requires referral to a reference laboratory with molecular capabilities, as many newer species are genetically distinct from established species yet have few or no distinguishing phenotypic characteristics. Correct identification is important in deciding the clinical relevance of a species and in the clinical management and treatment of patients with nocardial disease. This review characterizes the currently known pathogenic species of Nocardia, including clinical disease, drug susceptibility, and methods of identification.

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Clinical and Laboratory Features of the Nocardia spp. Based on Current Molecular Taxonomy

The aerobic actinomycetes are soil-inhabiting microorganisms that occur worldwide. In 1888, Nocard first recognized the pathogenic potential of this group of microorganisms. Since then, several aerobic actinomycetes have been a major source of interest for the commercial drug industry and have proved to be extremely useful microorganisms for producing novel antimicrobial agents. They have also been well known as potential veterinary pathogens affecting many different animal species. The medically important aerobic actinomycetes may cause significant morbidity and mortality, in particular in highly susceptible severely immunocompromised patients, including transplant recipients and patients infected with human immunodeficiency virus. However, the diagnosis of these infections may be difficult, and effective antimicrobial therapy may be complicated by antimicrobial resistance. The taxonomy of these microorganisms has been problematic. In recent revisions of their classification, new pathogenic species have been recognized. The development of additional and more reliable diagnostic tests and of a standardized method for antimicrobial susceptibility testing and the application of molecular techniques for the diagnosis and subtyping of these microorganisms are needed to better diagnose and treat infected patients and to identify effective control measures for these unusual pathogens. We review the epidemiology and microbiology of the major medically important aerobic actinomycetes. Images

The medically important aerobic actinomycetes: epidemiology and microbiology.

Two strains of a new gram-positive coryneform bacterium isolated from soil and from a sandstone surface are described. Strain 2002-39/1T (T = type strain) is a coccoid, nonmotile, non-acid-fast, microaerophilic organism. The menaquinones of this strain are MK-12 and MK-11, and the main components of the whole-cell sugars are glucose and rhamnose. No mycolic acids are present. The G+C content of the DNA is 74 mol%. Comparative 16S ribosomal DNA studies and a cell wall analysis revealed that this strain represents a new genus belonging to the group of actinomycetes that have diaminobutyric acid in their peptidoglycans. The second strain, strain ST54, which was isolated from a sandstone surface, had the same characteristic features as strain 2002-39/1T. The name Agrococcus jenensis gen. nov., sp. nov., is proposed for these organisms. The type strain is strain 2002-39/1, which has been deposited in the German Collection of Microorganisms and Cell Cultures as strain DSM 9580.

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Agrococcus jenensis gen. nov., sp. nov., a new genus of actinomycetes with diaminobutyric acid in the cell wall.

We propose two new genera, Amycolata and Amycolatopsis, to accommodate nocardioform actinomycetes having type IV cell wall composition and lacking mycolic acids. These two genera are distinguished from each other by phospholipid and menaquinone composition and phage sensitivity. The following species were assigned to the genus Amycolata: Amycolata autotrophica comb. nov. (type strain, strain ATCC 19727), Amycolata saturnea comb. nov. (type strain, strain NRRL B16172), and Amycolata hydrocarbonoxydans comb. nov. (type strain, strain NRRL B16171). The genus Amycolatopsis includes Amycolatopsis orientalis comb. nov. (type strain, strain ATCC 19795), Amycolatopsis orientalis subsp. lurida nom. rev., comb. nov., subsp. nov. (type strain, strain NRRL 2430), Amycolatopsis mediterranei comb. nov. (type strain, strain ATCC 13685), Amycolatopsis rugosa sp. nov. (type strain, strain ATCC 43014), and Amycolatopsis sulphurea sp. nov. (type strain, strain ATCC 27624).

Two New Genera of Nocardioform Actinomycetes: Amycolata gen. nov. and Amycolatopsis gen. nov.

A novel actinomycete was isolated from compost soil and was studied taxonomically and phylogenetically. Cells of this organism were gram positive, not acid fast, nonmotile, nonsporulating, irregular coccoid to short rod shaped, and microaerophilic. The cell wall peptidoglycan contained lysine and was cross-linked via an L-Lys←.-Ser←D-Asp interpeptide bridge. The major menaquinone was MK-8(H4). The polar lipids were phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and two unknown phospholipids. Mycolic acids were absent The cellular fatty acid profile was complex, with large amounts of saturated and monounsaturated straight-chain acids and smaller amounts of iso and anteiso branched-chain acids. The G+C content of the DNA was 66 mol%. Comparative 16S ribosomal DNA studies revealed that strain HKI0089T represents a novel lineage within Actinobacteria (32) distinct from all previously described genera and most closely related to members of the genera Kytococcus, Dermacoccus, and Dermatophilus of the family Dermatophilaceae. On the basis of our results, we suggest that strain HKI 0089 should be classified in a new genus and species, for which we propose the name Demetria terragena. The type strain and the only strain of the genus and species is HKI 0089 (DSM 11295).

Demetria terragena gen. nov., sp. nov., a New Genus of Actinomycetes Isolated from Compost Soil

Gray and Thornton's strain (ATCC 17041) of Mycobacterium coeliacum, here designated as the type strain of this species (which was later transferred to the genus Nocardia as Nocardia coeliaca), is a strain of M. rhodochrous (tentative generic assignment). The strain producing the antibiotic nocardin and similar strains, however, have been mistakenly labeled N. coeliaca. This report presents some of the characteristics of 27 of these mislabeled strains and demonstrates their close relationship to the type strain of N. autotrophica (Takamiya and Tubaki) Hirsch. The nocardin-producing strain and others like it are, therefore, assigned to N. autotrophica.

Nocardia coeliaca, Nocardia autotrophica, and the Nocardin Strain

Examination of 682 strains representing four species of mycobacteria (Mycobacterium phlei, M. smegmatis, M. fortuitum, and M. marinum) and seven species of nocardiae (Nocardia asteroides, N. caviae, N. brasiliensis, N. autotrophica, N. dassonvillei, N. madurae, and N. pelletieri) indicated that, with the exception of N. madurae and N. pelletieri, resistance to rifampin (20 μg/ml) is a useful property for describing these species. Resistance to lysozyme (300 to 500 U/ml) is taxonomically useful for delineating all 11 species.

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Dorothy A. Barnett

Papers

Nocardia coeliaca, Nocardia autotrophica, and the Nocardin Strain

Resistance to Rifampin and Lysozyme of Strains of Some Species of Mycobacterium and Nocardia as a Taxonomic Tool

Nocardia coeliaca, Nocardia autotrophica, and the nocardin strain. Int J Syst Bacteriol