''Nocardia'' is a

genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...

of weakly staining

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...

, catalase-positive, rod-shaped

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. 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 A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one o ...

when viewed with a dissecting

microscope A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...

, 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 Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

should be used during the staining procedure) due to the presence of intermediate-length mycolic acids in their

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

. Majority of strains possess the cord factor (trehalose 6-6' dimycolate), an important virulence factor. Four different Nocardia species

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. Nocardia asteroides

Virulence

The various species of ''Nocardia'' are

pathogenic In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ...

bacteria with low virulence; therefore clinically significant disease most frequently occurs as an

opportunistic infection An opportunistic infection is an infection that occurs most commonly in individuals with an immunodeficiency disorder and acts more severe on those with a weakened immune system. These types of infections are considered serious and can be caused b ...

in those with a weak immune system, such as small children, the elderly, and the

immunocompromised Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...

(most typically, HIV). Nocardial virulence factors are the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting ...

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 Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

by preventing the fusion of the phagosome with the

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

). An important virulence factor in many pathogenic strains of ''Nocardia'' is trehalose dimycolate, which is also found in the bacterial genus ''

Mycobacterium ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (''Mycobacterium tuberculo ...

''. This toxin can cause

cachexia Cachexia () is a syndrome that happens when people have certain illnesses, causing muscle loss that cannot be fully reversed with improved nutrition. It is most common in diseases like cancer, Heart failure, congestive heart failure, chronic o ...

, a form of muscle wasting.

Clinical disease and microbiological diagnosis

The most commonly encountered species are

Nocardia brasiliensis ''Nocardia brasiliensis'' is a species of ''Nocardia''. As with most members of Actinomycetota, they contain high guanine and cytosine Cytosine () (symbol C or Cyt) is one of the four nucleotide bases found in DNA and RNA, along with ade ...

, Nocardia cyriacigeorgica, Nocardia farcinica, and Nocardia nova. ''

Nocardia asteroides ''Nocardia asteroides'' is a species of ''Nocardia''. It can cause nocardiosis, a severe pulmonary infection in immunocompromised hosts. References Further reading * External linksType strain of ''Nocardia asteroides'' at Bac''Dive'' - the ...

'' is most frequently found species causing noncutaneous invasive disease. Most cases occur as an

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 Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

, the common symptoms of which include

cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...

, dyspnea (shortness of breath), and

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

. 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 Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...

and/or

brain abscess The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special sense ...

formation. ''Nocardia'' may also cause a variety of cutaneous infections such as

actinomycetoma Actinomycetoma is a chronic bacterial subcutaneous infection caused by '' Actinomyces'' that affect the skin and connective tissue. It is, therefore, a form of actinomycosis. Mycetoma is a broad term which includes actinomycetoma and eumycetoma ...

(especially ''N. brasiliensis''), lymphocutaneous disease,

cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...

, 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 An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

therapy with a

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

, 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 Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of ...

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

External links

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

MicrobeWiki's ''N. farcinica'' Page, Current as of June 2007
{{Authority control Acid-fast bacilli Mycobacteriales Bacteria genera Pathogenic bacteria