Nocardia cyriacigeorgica

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A Microbial Biorealm page on the genus Nocardia cyriacigeorgica

Classification

Higher order taxa

Domain: Bacteria

Phylum: Actinobacteria

Class: Actinobacteridae

Subclass: Actinomycetales

Order: Corynebacterineae

Suborder: Nocardiaceae

Family: Nocardia

Strain: Nocardia cyriacigeorgica

Species

NCBI: Taxonomy

Genus species: Nocardia cyriacigeorgica
Other Names: Nocardia cyriacigeorgici, Nocardia cyriacigeorgica corrig

Description and significance

Nocardia cyriacigeorgica is an aerobic, gram-positive, partially acid-fast, partially branched bacteria that primarily resides in soil, characterized by dry white colonies. Cyriacigeorgica, the species name, is named after the German town Gelsenkirchen, where the strain was first isolated (6). In 2001, Yassin et al. studied strain IMMIB D-1627, isolated from a patient with chronic bronchitis, and classified it as Nocardia cyriacigeorgici by utilizing a series of biochemical tests and phylogenetic evidence (7). Its genus name is derived from the work of scientist Edmond Nocard, who first isolated an aerobic actinomycete from cattle in 1888; Eppinger reported the first case of human infection, however, two years later (4). N. cyriacigeorgica, until recently, was believed to be a new, emerging pathogen. But in July 2007, Pactricia S. Conville and Frank G. Witebsky at the Department of Laboratory Medicine at the NIH utilized DNA-DNA hybridization method to conclude that Nocardia asteroides VI strains, common and well-recognized pathogen strains, belong to the Nocardia cyriacigeorgica species (2). Conville and Witebsky identified the Nocardia asteroides drug pattern VI by its reference number ATCC 14759 based on drug susceptibility patterns(2); they analyzed the 1,384 base pair regions of the 16S rRNA gene and found that the reference strain of N. asteroides drug pattern type VI to be identical to the N. cyriacigeorgica strain (2). Wallace et al. discovered that strain VI showed resistance to penicillin and susceptibility to broad-spectrum cephalosporins (12). It was later placed into the subspecies N. asteroides sensu stricto along with N. asteroides I, and IV, and is determined to be predominantly human pathogens (10). Additionally, N. asteroides VI can be also referred to as N. asteroides complex, a term which also includes other similar species such as N. Farcinica, N. Nova, and N. Abscessus(11). Because of its intrinsic multiple drug resistant nature, its genomic structure, its cell structure, and its threat to immunosuppressed individuals, Nocardia isolates are studied to find the optimal choice of treatment. Fast and accurate identification of the species of Nocardia responsible for Nocardiosis in affected individuals is thought to play a large role in the diagnosis and treatment of Nocardiosis (17).

Genome structure

The genomic structure for Nocardia cyriacigeorgica is privately funded and not open to the public (13). N. cyriacigeorgica is 99.5% similar in its HSP gene sequence as N. asteroides drug pattern VI, with only two base differences in a 373-bp region; the amino acids sequences are identical (2). Recent DNA hybridization studies have shown that the two are related and they are now believed to belong to the same species. The total genome size of N. asteroides is 7.5 Mb with a large linear plasmid of 220 kb (8). To date, the only complete genome that is available to the general public is Nocardia farcinica (14), partly due to its homogeneous nature.

Nocardia farcinica has one circular chormosome and two circular plasmids. Its circular chromosome consists of 6,021,225 bp and two circular plasmids, pNF1 and pNF2 consists of 184,027bp and 87,093 bp respectively. Since Nocardia farcinica is a soil bacteria, it contains various proteins which helps it to adapt to diverse soil environment, including short-chain dehydrogenases and ABC transporters. However, it lacks PE/PPE/PGRS family proteins, which is for pathogenicity and intracellular growth, due to its ability to inhabit both soil and tissue. Additionally, gene duplication was found as one of the reasons for its drug resistance abilities. N. farcinica possesses two β subunits for RNA polymerase, designated rpoB and rpoB2. This is first case ever reported in which there are two rpoB genes on one bacterial genome (15).

Cell structure and metabolism

The Nocardia species can be distinguished phenotypically. For example, Nocardia are characterized by their filamentous, branched shape and the presence of aerial hyphae (11). At the early stage of development, N. cyriacigeorgica has irregular, white aerial hyphae. Later, these hyphae will start to become rod-shaped, which is typical of the Nocardia family (7). Yassin et al. discovered that N. cyriacigeorgica contained long mycolic acids with 46-54 carbon atoms (7). Studies have shown that N. asteroides strains “contain meso-diaminopimelic acid as a cell wall diamino acid and to have galactose and arabinose as characteristic whole-cell sugars” (18). Due to its acid-fastness, N. cyriacigeorgica grows slowly, and those individuals infected must be on antibiotics for an extended amount of time (17) Additionally, its slow growth presents a problem for susceptibility testing (17).

Being a soil bacteria, N. cyriacigeorgica utilize a variety of compounds for carbon source and energy(7). Its primary source for energy and carbon include acetate, gluconate, and sucrose, and acetamide for source of carbon and nitrogen. During nitrogen assimilation, glutamate and glutamine is formed. N. asteroides utilizes the GA/GOGAT pathway to form glutamine, which contains the enzymes glutamine synthetase and glutamate synthase (9). These enzymes catalyzes glutamate from α-ketogluterate and ammonia (7).

Ecology, Pathology, and Antibiotic Susceptibility

Nocardia cyriacigeorgica are found primarily in soil, but also inhabits humans and sometimes associated with water (11). Nocardia cyriacigeorgica, or N. asteroides VI, causes most of the cases of human infection (11)and one of the factors that causes Nocardiosis(17). Some diseases as a result of this pathogen are, but not limited to: chronic bronchitis (10), brain abscess (5), but most commonly pulmonary disease (14). N. cyriacigeorgica is considered to be an opportunistic infection, that is, individuals who are immunosuppressed are especially susceptible to Nocardia cyriacigeorgica (3). In a study analyzing Nocardial infections in Japan from 1992-2001, 22.4% of those infected were individuals on immunosuppressive agents, followed by SLE therapy: 3.6%, cancer: 6.6%, diabetes: 3.6%, tuberculosis: 3.3%, and AIDS 2.0%. Nocardia asteroides complex, which includes N. beijingensis and N. cyriacigeorgica, was responsible for 71.4% of the lung and 8.5% to the skin (3)(11). There is also studies which suggests that N. asteroides to be an etiological agent of Parkinson’s disease (15), since it was able to spread to the brain via blood. Being a soil bacteria, most pulmonary infections are through inhalation. Areas that are dry and windy, like the US, are primary locations for infection, since the winds enhances the relocation of the microbe (11)
Detection of Nocardia cyriacigeorgica is limited to gram staining and smears and cultures. Even the acid-fast stains are only used to confirm whether or not the specimen is acid-fast, and not as a definitive tool of diagnosis.

Although virulence factors for Nocarida cyriacigeorgica is currently unknown, there are 6 copies of the Mce proteins found on another species in the Nocardia family: Nocardia farcinica (15). Its c-terminus is also highly homologous to the protein Nfa34810, which plays an important role in invasion and adherence to host cells.

Once N. cyriacigeorgica invades its host, it can inhibit phagosome-lysosome fusion in phagocytes, modifying its functions, and grow within phagocytes. Some immuno-response to the invading microbe includes T-cells and macrophages. It is also believed to cause neurodegenerative diseases such as Parkinson’s, thus making it an etiological disease (16).

The diagnosis and treatment of Nocardiosis, caused by the Nocardia asteroides complex can be incredibly difficult to treat. Members belonging to the complex, N. cyriacigeorgica included, although susceptible to treatments such as co-trimoxazole, show different responses to other treatment. Isolating species are generally time consuming and complex based on microscopic techniques or phenotypically (17). N. asteroides is resistant to ampicillin, but susceptible to extended-spectrum cephalosporins and imipenem (10).

Current Research

Recently, Patricia S. Conville and Frank G. Witebsky determined that Nocardia asteroides Drug Pattern Type VI are members of Nocardia cyriacigeorgica. They compared drug strain ATCC 14759 to a strain of N. cyriacigeorgica by performing DNA-DNA hybridazation. Later, a comparison sequence analysis of the 16S rRNA showed that there was a 99.5% similarity between the HSP gene sequence. Additionally, the amino acid sequences of the HSPs was identical. Further comparison of a region in the secA1 gene whosed a 99.1% similarity between the two strains.

Additionally, Sameer Elsayed et al. reported two cases of Nocardia cyriageorgica bloodstream infection in humans; both cases illustrating the propensity of infection in immunocompromised patients: one did not survive. Their studies showed that the isolated strains were susceptible to TMP-SMX imipenenem, and amikacin.

Recent studies also suggests that one of the reasons for the high mortality rates of Nocardiosis could be the difficulty in identifying the strain on a timely fashion. Since N. asteroides complex contains a many strains, the isolation process and susceptibility process takes time because of its slow growth rate. Furthermore, all species shows different patterns in their responses to treatment. This further complicates in the identification of the unknown species.

References

(1) "Nocardia Cyriacigeorgica". NCBI Taxonomy Browser. [1].

(2)Conville, Patricia S, Witebsky, Frank G., “Organisms Designated as Nocardia asteroides Drug Pattern Type VI Are Members of the Species Nocardia cyriacigeorgica” Journal of Clinical Microbiology. July, 2007. p. 2257-2259 Link to Article

(3)Kageyma, A., K. Yazawa, J. Ishikawa, K. Hotta, K. Nishimura & Y. Mikami, “Nocardial infections in Japan from 1992 to 2001, including the first report of infection by Nocardia transvalensis” European Journal of Epidemiology . 2004 19: p. 383-389Link to Article

(4)Elsayed, S., Kealey, A., Coffin, C.S., Read, R., Megran, D., & Zhang, K., “Nocardia cyriacigeorgica Septicemia” Journal of Clinical Microbiology. Jan. 2006, p. 280-282 Link to Article

(5)Barnaud, G., Deschamps C., Manceron, V., Mortier, E., Laurent, F., Bert, F., Boiron, P., Vinceneux, P., & Branger, C. “Brain Abscess Caused by Nocardia cyriacigeorgica in a Patient with Human Immunodeficiency Virus Infection" Journal of Clinical Microbiology. Sept. 2005 p. 4895-4897 Link to Article

(6)Palaniappan, C., Gunasekaran, M., “Purification and Properties of Glutamine Synthetase from Nocardia asteroides" Current Microbiology . 1995, vol. 31, p. 193-198Link to Article

(7)Yassin, A.F., Rainey, F.A., & Steiner, U., “Nocardia cyriacigeorgici sp. Nov." International Journal of Systematic and Evolutionary Microbiology . 2001, vol. 51 p. 1419-1423 Link to Article

(8)Redenbach, M., Scheel, J., & Schmidt, U., “Chromosome topology and genome size of selected actinomycetes species” Antoine van Leeuwenhoek International Journal of General and Molecular Microbiology. 2000, Vol. 78 p. 227-235 Link to Article

(9)Palaniappan, C., Gunasekaran, M., “Ammonium assimilation in Nocardia asteroides” Mycopathologia . 1993 Vol: 124, p. 69-72Link to Article

(10)Poirel, L., Laurent, F., Naas, T., Labia, R., Boiron, P., & Nordmann, P., “Molecular and Biochemical Analysis of AST-1, a Class A β-Lactamase from Nocardia asteroides Sensu Stricto” Antimicrobial Agents and Chemotheraphy. Mar. 2001 p. 878-882Link to Article

(11)Saubolle, M.A., & Sussland, D., “MINIREVIEW-Nocardiosis: Review of Clinical and Laboratory Experience” Journal of Clinical Microbiology. Oct. 2003 p. 4497-4501Link to Article

(12)Wallace, R.J. JR., Steele, L.C., Sumter, G., & Smith, J.M., “Antimicrobial susceptibility patterns of Nocardia asteroides” Antimicrobial Agents and Chemotheraphy. Dec. 1988, p. 1776-1779Link to Article

(13)Genoscope, http://www.genoscope.cns.fr/agc/mage/wwwpkgdb/MageHome/index.php?webpage=mage

(14)Ishikawa, J., Hoshino, Y., Ishino, k., Kurita, H., Chiba, K., Fujii, S., Hattori M., Yamashita, A., Mikami, Y., Yazawa, K., and Takeda, k. “Nocardia Farcinica Genome Project Page” Link to Page

(15)Ishikawa, J., Yamashita, A., Mikami, Y., Hoshino, Y., Kurita, H., Hotta, K., Shiba, T., and Hattori, M., “The Complete genomic sequence of Nocardia farcinica IFM 10152” Communicated by Satoshi Omura, Kitasato Institute, Tokyo, Japan. Aug. 2004Link to Article

(16)Beaman, B.L., and Beaman L., “Nocardia species: host-parasite relationships” Clinical Microbiology Review . April 1994, vol. 7(2), p. 213-264Link to Article

(17)Munoz, J., Mirelis, B., Aragon, L.M., Gutierrez, N., Sanchez, F., Espanol, M., Esparcia, O., Gurgui, Mn., Domingo, P., and Coll, P., “Clinical and microbiological features of nocardiosis 1997-2003” Journal of Medical Microbiology. 2007, vol. 56, p. 545-550Link to Article

(18)Hideki Yamamura, Masayuki Hayakawa, Youji Nakagawa, and Yuzuru Iimura “Characterization of Nocardia asteroides Isolates from Different Ecological Habitats on the Basis of Repetitive Extragenic Palindromic-PCR Fingerprinting” applied and Environmental Microbiology 2004 May; 70(5): 3149–3151 Link to Article

Edited by Yizhao Li student of Rachel Larsen