Nocardia Brain Autopsy

''Nocardia'' is a genus of weakly staining Gram-positive, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (appearing similar to fungi, but being truly bacteria). It contains a total of 85 species. Some species are nonpathogenic, while others are responsible for nocardiosis. ''Nocardia'' species are found worldwide in soil rich in organic matter. In addition, they are oral microflora found in healthy human gingiva, as well as periodontal pockets. Most ''Nocardia'' infections are acquired by inhalation of the bacteria or through traumatic introduction through openings in epithelial barriers.

Culture and staining

''Nocardia'' colonies have a variable appearance, but most species appear to have aerial hyphae when viewed with a dissecting microscope, particularly when they have been grown on nutritionally limiting media. ''Nocardia'' grow slowly on nonselective culture media, and are strict aerobes with the ability to grow in a wide temperature range. Some species are partially acid-fast (meaning a less concentrated solution of sulfuric or hydrochloric acid should be used during the staining procedure) due to the presence of intermediate-length mycolic acids in their cell wall. Majority of strains possess the cord factor (trehalose 6-6' dimycolate), an important virulence factor.

They are catalase positive and can grow easily on the most commonly used media with colonies becoming evident in 3–5 days. However, prolonged incubation periods (2–3 weeks) are sometimes needed.

Virulence

The various species of ''Nocardia'' are pathogenic bacteria with low virulence; therefore clinically significant disease most frequently occurs as an opportunistic infection in those with a weak immune system, such as small children, the elderly, and the immunocompromised (most typically, HIV). Nocardial virulence factors are the enzymes catalase and superoxide dismutase (which inactivate reactive oxygen species that would otherwise prove toxic to the bacteria), as well as a "cord factor" (which interferes with phagocytosis by macrophages by preventing the fusion of the phagosome with the lysosome).

An important virulence factor in many pathogenic strains of ''Nocardia'' is trehalose dimycolate, which is also found in the bacterial genus ''Mycobacterium''. This toxin can cause cachexia, a form of muscle wasting.

Clinical disease and microbiological diagnosis

The most commonly encountered species are Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica, and Nocardia nova. ''Nocardia asteroides'' is most frequently found species causing noncutaneous invasive disease. Most cases occur as an opportunistic infection in immunocompromised patients. ''N. brasiliensis'' is the most common species causing cutaneous nocardiosis. ''N. caviae'' is another species of medical interest. The genus is acid-fast to some degree, it stains only weakly Gram positive.

The most common form of human nocardial disease is a slowly progressive pneumonia, the common symptoms of which include cough, dyspnea (shortness of breath), and fever. It is not uncommon for this infection to spread to the pleura or chest wall. Pre-existing pulmonary disease, especially pulmonary alveolar proteinosis, increases the risk of contracting a ''Nocardia'' pneumonia. Every organ can be affected if a systemic spread takes place.

''Nocardia'' species are deeply involved in the process of encephalitis as one of its main pathogenic effects. In about 25–33% of people ''Nocardia'' infection takes the form of encephalitis and/or brain abscess formation. ''Nocardia'' may also cause a variety of cutaneous infections such as actinomycetoma (especially ''N. brasiliensis''), lymphocutaneous disease, cellulitis, and subcutaneous abscesses.

''Nocardia'' isolation from biological specimens can be performed using an agar medium enriched with yeast extract and activated charcoal (BCYE), the same used for ''Legionella'' species. Selective media for mycobacteria or fungi can also be inoculated. The most suitable specimens are the sputum, or when clinically necessary, bronchoalveolar lavage or biopsy. Further biochemical tests for species identification are not routinely performed. Serological or cutaneous tests are not available.

Treatment

In most patients with ''Nocardia'' infection, the combination of antibiotics is needed.
Antibiotic therapy with a sulfonamide, most commonly trimethoprim-sulfamethoxazole, is the treatment of choice. Retrieved on January 3, 2009. Freely available with registration. People who take trimethoprim-sulfamethoxazole for other reasons, such as prevention of ''Pneumocystis jirovecii'' infection, appear to have fewer ''Nocardia'' infections, although this protective effect has been considered unreliable, and some studies have disputed it altogether. Minocycline is usually substituted when a sulfa cannot be given; high-dose imipenem and amikacin have also been used in severe or refractory cases. Linezolid appears to be highly effective against ''Nocardia'', but it is very expensive and may cause severe adverse effects.

Antibiotic therapy is continued for six months (in immunocompetent people) to a year (in immunosuppression), and may need to be continued indefinitely. Proper wound care is also critical.

Genetics

Although ''Nocardia'' has interesting and important features such as production of antibiotics and aromatic compound-degrading or -converting enzymes, the genetic study of this organism has been hampered by the lack of genetic tools. However, practical ''Nocardia''–''E. coli'' shuttle vectors have been developed recently.

The genera ''Nocardia'' and ''Rhodococcus'' have been found to be closely related, supported by two conserved signature indels consisting of a one-amino-acid deletion in the alpha subunit of acetyl coenzyme A carboxylase (ACC), and a three-amino-acid insertion in a conserved region of an ATP-binding protein that are specifically shared by species from these two genera. In addition, 14 hypothetical conserved signature proteins have been identified which are unique to the genera ''Nocardia'' and ''Rhodococcus''.

Species

''Nocardia'' comprises the following species:

* '' N. abscessus'' Yassin et al. 2000
* '' N. acididurans'' Sirireung et al. 2021
* '' N. aciditolerans'' Golinska et al. 2013
* '' N. acidivorans'' Kämpfer et al. 2007

* '' N. africana'' Hamid et al. 2001
* '' N. alba'' Li et al. 2004
* '' N. albiluteola'' Shan et al. 2022
* "'' N. alni''" Nouioui et al. 2022
* '' N. altamirensis'' Jurado et al. 2008
* '' N. amamiensis'' Yamamura et al. 2007

* '' N. amikacinitolerans'' Ezeoke et al. 2013
* '' N. anaemiae'' Kageyama et al. 2005
* '' N. aobensis'' Kageyama et al. 2005
* '' N. araoensis'' Kageyama et al. 2004
* "'' N. argentinensis''" Cone et al. 1989
* '' N. arizonensis'' Lasker et al. 2017
* '' N. artemisiae'' Zhao et al. 2011
* '' N. arthritidis'' Kageyama et al. 2005
* '' N. asiatica'' Kageyama et al. 2004
* '' N. asteroides'' (Eppinger 1891) Blanchard 1896 (Approved Lists 1980)
* '' N. aurantia'' Benndorf et al. 2020
* '' N. aurantiaca'' Kanchanasin et al. 2020
* '' N. aurea'' Fang et al. 2019

* '' N. barduliensis'' Nouioui et al. 2021
* '' N. beijingensis'' Wang et al. 2001
* '' N. bhagyanarayanae'' corrig. Vaddavalli et al. 2014

* '' N. blacklockiae'' Conville et al. 2009

* "'' N. boironii''" Gilquin et al. 2016
* '' N. bovistercoris'' Zhang et al. 2021
* '' N. brasiliensis'' (Lindenberg 1909) Pinoy 1913 (Approved Lists 1980)
* '' N. brevicatena'' (Lechevalier et al. 1961) Goodfellow and Pirouz 1982
* '' N. caishijiensis'' Zhang et al. 2003
* '' N. calcarea'' Metcalfe and Brown 1957 (Approved Lists 1980)
* '' N. callitridis'' Kaewkla and Franco 2010
* '' N. camponoti'' Liu et al. 2016

* '' N. carnea'' (Rossi Doria 1891) Castellani and Chalmers 1913 (Approved Lists 1980)
* '' N. casuarinae'' Ghodhbane-Gtari et al. 2015
* '' N. cavernae'' Li et al. 2017

* '' N. cerradoensis'' Albuquerque de Barros et al. 2003
* '' N. coeliaca'' (Gray and Thornton 1928) Waksman and Henrici 1948 (Approved Lists 1980)
* '' N. coffeae'' Nammali et al. 2022
* '' N. colli'' Zhou et al. 2020
* '' N. concava'' Kageyama et al. 2005

* '' N. coubleae'' Rodríguez-Nava et al. 2007
* '' N. crassostreae'' Friedman et al. 1998

* '' N. cyriacigeorgica'' corrig. Yassin et al. 2001

* '' N. donostiensis'' Ercibengoa et al. 2020
* '' N. elegans'' Yassin and Brenner 2005
* '' N. endophytica'' Xing et al. 2011
* '' N. exalbida'' Iida et al. 2006
* '' N. farcinica'' Trevisan 1889 (Approved Lists 1980)
* '' N. flavorosea'' Chun et al. 1998
* '' N. fluminea'' Maldonado et al. 2001

* '' N. gamkensis'' Le Roes and Meyers 2007
* '' N. gipuzkoensis'' Nouioui et al. 2021
* '' N. globerula'' (Gray 1928) Waksman and Henrici 1948 (Approved Lists 1980)
* '' N. goodfellowii'' Sazak et al. 2012
* '' N. grenadensis'' Kämpfer et al. 2012
* '' N. halotolerans'' Nikou et al. 2015
* '' N. harenae'' Seo and Lee 2006
* '' N. heshunensis'' Huang et al. 2017
* '' N. higoensis'' Kageyama et al. 2004
* '' N. huaxiensis'' Zhuang et al. 2021

* '' N. ignorata'' Yassin et al. 2001
* '' N. inohanensis'' Kageyama et al. 2004

* '' N. iowensis'' Lamm et al. 2009

* '' N. jejuensis'' Lee 2006
* '' N. jiangsuensis'' Bai et al. 2016
* '' N. jiangxiensis'' Cui et al. 2005
* '' N. jinanensis'' Sun et al. 2009
* '' N. kroppenstedtii'' Jones et al. 2014
* '' N. kruczakiae'' Conville et al. 2005
* '' N. lasii'' Liu et al. 2017
* "'' N. levis''" Kavitha et al. 2009
* '' N. lijiangensis'' Xu et al. 2006
* "'' N. lurida''" Theriault et al. 1986
* '' N. macrotermitis'' Benndorf et al. 2020
* '' N. mangyaensis'' Yang et al. 2019

* '' N. mexicana'' Rodríguez-Nava et al. 2006
* '' N. mikamii'' Jannat-Khah et al. 2010
* '' N. miyunensis'' Cui et al. 2005
* '' N. neocaledoniensis'' Saintpierre-Bonaccio et al. 2004
* '' N. niigatensis'' Kageyama et al. 2004
* '' N. ninae'' Laurent et al. 2007
* '' N. niwae'' Moser et al. 2011
* "'' N. noduli''" Nouioui et al. 2022
* '' N. nova'' Tsukamura 1983

* '' N. otitidiscaviarum'' corrig. Snijders 1924 (Approved Lists 1980)
* "'' N. panacis''" Hu et al. 2020
* "'' N. paratuberculosis''" Tsukamura 1982
* '' N. paucivorans'' Yassin et al. 2000

* "'' N. phenotolerans''" Yassin et al. 1988
* '' N. pigrifrangens'' Wang et al. 2004

* '' N. pneumoniae'' Kageyama et al. 2004
* '' N. polyresistens'' Xu et al. 2005
* '' N. pseudobrasiliensis'' Ruimy et al. 1996
* '' N. pseudovaccinii'' Kim et al. 2002
* '' N. puris'' Yassin et al. 2003
* '' N. rayongensis'' Tanasupawat et al. 2016

* '' N. rhamnosiphila'' Everest et al. 2012
* '' N. rhizosphaerae'' Wang et al. 2015
* '' N. rhizosphaerihabitans'' Ding et al. 2018

* '' N. salmonicida'' (ex Rucker 1949) Isik et al. 1999

* '' N. seriolae'' Kudo et al. 1988
* '' N. shimofusensis'' Kageyama et al. 2004
* '' N. shinanonensis'' Matsumoto et al. 2016
* '' N. sienata'' corrig. Kageyama et al. 2004
* "'' N. simplex''" Jirasripongpun 2002

* '' N. speluncae'' Seo et al. 2007
* '' N. stercoris'' Zhao et al. 2020
* "'' N. suismassiliense''" Fellag et al. 2018

* '' N. sungurluensis'' Camas et al. 2014
* '' N. takedensis'' Yamamura et al. 2005

* '' N. tenerifensis'' Kämpfer et al. 2004
* '' N. tengchongensis'' Li et al. 2017
* '' N. terpenica'' Hoshino et al. 2007
* "'' N. terrae''" Kanchanasin et al. 2021
* '' N. testacea'' corrig. Kageyama et al. 2004

* '' N. thailandica'' Kageyama et al. 2005
* '' N. thraciensis'' Sazak et al. 2012
* '' N. transvalensis'' Pijper and Pullinger 1927 (Approved Lists 1980)

* '' N. uniformis'' (ex Marton and Szabó 1959) Isik et al. 1999
* '' N. vaccinii'' Demaree and Smith 1952 (Approved Lists 1980)
* '' N. vermiculata'' Kageyama et al. 2005
* '' N. veterana'' Gürtler et al. 2001
* '' N. vinacea'' Kinoshita et al. 2002
* '' N. vulneris'' Lasker et al. 2015
* '' N. wallacei'' Conville et al. 2009
* '' N. xestospongiae'' Thawai et al. 2017
* '' N. xishanensis'' Zhang et al. 2004
* '' N. yamanashiensis'' Kageyama et al. 2004
* '' N. yunnanensis'' Zhang et al. 2019
* '' N. zapadnayensis'' Ozdemir-Kocak et al. 2016
* '' N. zhihengii'' Huang et al. 2019

Nomenclature

The genus was named for Edmond Nocard (1850-1903), a French 19th-century veterinarian and biologist.

The genus was circumscribed by Vittore Benedetto Antonio Trevisan di Saint-Léon in Ann. Inst. Pasteur vol.2 (Issue 6) on page 295 in 1888.

References

Further reading

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External links

Genome sequence of ''N. farcinica'' IFM 10152

MicrobeWiki's ''N. farcinica'' Page, Current as of June 2007

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Acid-fast bacilli
Mycobacteriales
Bacteria genera
Pathogenic bacteria