Nocardia Barduliensis
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''Nocardia'' is a
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...
of weakly staining Gram-positive, 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 among ...
. It forms partially acid-fast 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 Nocardiosis is an infectious disease affecting either the lungs (''pulmonary nocardiosis'') or the whole body (''systemic nocardiosis''). It is due to infection by a bacterium of the genus ''Nocardia'', most commonly ''Nocardia asteroides'' or '' N ...
. ''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 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 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 mech ...
. Majority of strains possess the
cord factor Cord factor, or trehalose dimycolate, is a glycolipid molecule found in the cell wall of '' Mycobacterium tuberculosis'' and similar species. It is the primary lipid found on the exterior of ''M. tuberculosis'' cells. Cord factor influences the ...
(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 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 germ ...
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 ca ...
; 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 immune ...
in those with a weak immune system, such as small children, the elderly, and the immunocompromised (most typically, HIV). Nocardial virulence factors are the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s
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 me ...
(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 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 mem ...
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 prot ...
).


Clinical disease and microbiological diagnosis

The most commonly encountered species are Nocardia brasiliensis, 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
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 immune ...
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 severity ...
, the common symptoms of which include cough, dyspnea (shortness of breath), and
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
. 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 bet ...
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 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, hallucinations, ...
and/or brain abscess 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 unde ...
(especially ''N. brasiliensis''), lymphocutaneous disease, cellulitis, and subcutaneous
abscess An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
es. ''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 interv ...
(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 bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
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 unreactive. ...
, most commonly
trimethoprim-sulfamethoxazole Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
, 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 Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...
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 enzy ...
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 multi ...
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, van ...
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 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-comprom ...
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 Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
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 polyg ...
by Vittore Benedetto Antonio Trevisan di Saint-Léon in Ann. Inst. Pasteur vol.2 (Issue 6) on page 295 in 1888.


References


Further reading

* * * * *


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