''Nocardia'' is a

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial n ...

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. Gram-positive bac ...

, catalase-positive, rod-shaped

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

. It forms partially

acid-fast Acid-fastness is a physical property of certain bacterial and eukaryotic cells, as well as some sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining procedures. Once stained as part of a s ...

beaded branching filaments (acting as 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 gingiva, as well as periodontal pockets. Most ''Nocardia'' infections are acquired by inhalation of the bacteria or through traumatic introduction.

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 or ...

when viewed with a dissecting

microscope A microscope () is a 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 means being invisibl ...

, 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

(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 acid Mycolic acids are long fatty acids found in the cell walls of the Mycolata taxon, a group of bacteria that includes '' Mycobacterium tuberculosis'', the causative agent of the disease tuberculosis. They form the major component of the cell wall o ...

s in their

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mec ...

. 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 ( el, πάθος, "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 ger ...

bacteria with low

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

; therefore clinically significant disease most frequently occurs as an

opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immun ...

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

immunocompromised Immunodeficiency, also known as immunocompromisation, 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 a ...

(most typically, HIV). Nocardial

virulence factor Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the followin ...

s are the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

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 t ...

and

superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen m ...

(which inactivate

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen ...

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 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 phagocytosis i ...

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

by preventing the fusion of the

phagosome In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell me ...

with the

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane ...

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

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 inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...

, the common symptoms of which include

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

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

(shortness of breath), and

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

. It is not uncommon for this infection to spread to the

pleura The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips ...

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, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hal ...

and/or

brain abscess Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal b ...

formation. ''Nocardia'' may also cause a variety of cutaneous infections such as actinomycetoma (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 "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an inter ...

(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 structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactiv ...

, 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 Imipenem (trade name Primaxin among others) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase en ...

and amikacin have also been used in severe or refractory cases.

Linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vanco ...

appears to be highly effective against ''Nocardia'', but it is very expensive and may cause severe

adverse effects An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

. Antibiotic therapy is continued for six months (in

immunocompetent In immunology, immunocompetence is the ability of the body to produce a normal immune response following exposure to an antigen. Immunocompetence is the opposite of immunodeficiency (also known as ''immuno-incompetence'' or being ''immuno-comp ...

people) to a year (in

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

), 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 Conserved signature inserts and deletions (CSIs) in protein sequences provide an important category of molecular markers for understanding phylogenetic relationships. CSIs, brought about by rare genetic changes, provide useful phylogenetic markers ...

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 In geometry, the circumscribed circle or circumcircle of a polygon is a circle that passes through all the vertices of the polygon. The center of this circle is called the circumcenter and its radius is called the circumradius. Not every po ...

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
{{Taxonbar, from=Q135175 Acid-fast bacilli Mycobacteriales Bacteria genera