Streptococcus zooepidemicus

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A Microbial Biorealm page on the genus Streptococcus zooepidemicus

Classification

Higher order taxa

Bacteria; Firmicutes; Bascilli; Lactobacillales; Streptococcaceae; Streptococcus

Species

NCBI: Taxonomy

Streptococcus equi

Subspecies

zooepidemicus

Other names

“Animal pyogenes, type A” [Edwards 1934]
“Streptococcus pyogene animalis” [Seelemann 1942]
“Streptococcus equi subsp. zooepidemicus” [Farrow and Collins 1985]

Type Strains

ATCC 43079
DSM 20727
NCDO 1358

Description and significance

Streptococcus zooepidemicus is one of the two subspecies of Streptococcus equi; it is suggested to be the species from which subspecies equi has been derived (5). Subspecies zooepidemicus is a normal bacterial flora in horses. It is isolated from wound infections of horses, and it has been isolated from other mammals such as cows, rabbits, and swine (3). In some cases, subspecies zooepidemicus is also isolated from humans through throat swabs (4). It occasionally causes human infection that can be traced back to contact with horses or consumption of unpasteurized dairy products (4).

Like other streptococci, Streptococcus zooepidemicus is a non-motile, non-sporulating, encapsulated, gram-positive, catalse-negative, and coccoid bacterium. It is a beta hemolytic streptococcus that produces hyaluronic acid but not streptolysin O and occurs in pairs or long chains (2,3). It is also lactose positive and is capable of fermenting sorbitol but not trehalose (3, 28). As a member of the group C streptococci, this microorganism is highly susceptible to penicillin (3); thus, patients diagnosed with infections associated with S. zooepidemicus are usually given that antibiotic for cure (6,7). Seriously ill patient may be given amynoglycoside along with penicillin to increase the sufficiency of cure (6). S. zooepidemicus is also highly susceptible to antibiotics such as ampicillin, nitrofurans, and erythromycin. In contrast, it has excellent resistance against amikacin, triple sulfa, and tribrissen (19).

Genome structure

Although the shotgun sequencing is complete with an available database of reads, the genome project of Streptococcus zooepidemicus is still in progress. At present, the genome size of this microorganism is about 2.3 Mb with a G+C content of approximately 41%, and 33,640 reads totaling 23.629Mb covering theoretically 99.99% of the genome (14). The similarity between the DNA of the two subspecies, zooepidemicus and equi, is over 92%. However, their biological behaviors in horses differ significantly. Subspecies zooepidemicus is a commensal of equine nasopharynx and external genitalia and causes infections in various areas, while subspecies equi is a contributing agent that causes strangles (3, 18).

In addition, S. zooepidemicus strains have SzP, a surface M-like protein with diversity in gene sequence and size. In terms of SzP types, isolates from healthy tonsil and isolates from tonsil infected by pneumonia are similar. However, these SzP proteins are of different types, and they contribute to the pathogenesis of subspecies zooepidemicus. Some SzP genotypes are suspected to infect specific locations such as the genital site or the respiratory site. By analyzing szp, scientists have discovered the possible migration of the szp of a single S. zooepidemicus strain from one location to another at a high rate in horses. For instance, it is capable of transferring itself from upper respiratory tract to lower respiratory tract through long-distance transportation. Although obtained from the same single swab sample, two clones of S. zooepidemicus show genetic variation from each other and thus demonstrate the great diversity of szp genotypes (29). SzP proteins may have an antiphagocytic role similar to that of the M proteins in group A streptococci (GAS) in the case of causing human infection. The SzP proteins not only share structural similarities with the M proteins but also stimulate opsonic antibodies just like the M proteins do (13).

Cell structure and metabolism

Cell wall

In general, Lancefield group C streptococci (GCS) have cell walls consisting of group-specific carbohydrate and mucopeptide polymer (20). The group-specific antigens of GCS are polysaccharides that are made up of hexoamine and rhamnose. Unlike group A streptococci (GAS), GCS carbohydrate has a terminal antigenic determinant of N-acetyl-galactosamine (3). A unique strain of Lancefield group C Streptococcus zooepidemicus, Streptococcus zooepidemicus 4881, is known to have the capability of producing zoocin A, which is a domain-structured peptidoglycan hydrolase (30). It can degrade cell walls of similar streptococcal species, such as Streptococcus pyogenes strains and mutans streptococcal strains with an exception of Streptococcus rattus, which is able to bind to zoocin A without losing its resistance against hydrolysis (30). Other than strain 4881 itself, zoocin A can even produce inhibitory activity against Streptococcus zooepidemicus strains (31). Those strains are zoocin A-sensitive because their peptidoglycan contains tri-alanine cross-links, whereas other strains, namely S. oralis and of Lactococcus, are resistant to zoocin A due to their direct covalent and single D-Asp amino acid cross-links (31). There are several possible explanations for the unaffected state of S. zooepidemicus 4881 by its own product. First of all, zoocin A may not be able to recognize specific cell surface determinants on S. zooepidemicus strain 4881 and therefore its bacteriolytic ability cannot take effect. Second, strain 4881 may have tough peptidoglycan cross-links that are not cleavable by zoocin A. Finally, this strain may also possess the ability to produce zoocin A immunity factors (zif), which can protect itself from the effect of its product (31).

Metabolism

In the process of fermentation, S. zooepidemicus produces both hyaluronic acid and lactic acid. The latter is a factor that can regulate the productivity of hyaluronic acid by lowering the efficiency of substrate converting to hyaluronic acid (32). However, since the synthesis of hyaluronic acid is “a significant energetic burden upon the microorganism” (33), excessive cloning of native NADH oxidase gene will occur to raise the catabolic energy yield when extracting glucose under aerobic condition. These NADH oxidase level will decrease and prevent lactic acid and ethanol formation, respectively (33). Studies have also shown that the polyhydroxybutyrate (PHB) synthesis pathway can regulate hyaluronic production metabolism by affecting the cellular oxidation/reduction potential, which will in turn affect the potential-sensitive lactic acid fermentation (33).

Ecology

Streptococcus zooepidemicus is facultively anaerobic and host-associated. Its optimal temperature for growth is 37° C. It is a commensal of horses, and its host range also includes swine, cattle, poultry, and human (21). This microorganism can be found in various parts of horses and cattle, including nasopharynx, tonsils, respiratory tract, and the genital muscous membranes (24). In fact, subspecies zooepidemicus is the one bacterium that is most commonly recovered from wounds and abscesses, guttural pouches, transtracheal washes (TTW), and uterus of horses (12).

Pathology

Animals

Streptococcus zooepidemicus is a pathogen of animals primarily affecting horses, in whom it can cause diseases in the upper respiratory tract, uterus, umbilicus, and wounds (5). In cows, S. zooepidemicus can cause mastitis (3), an inflammation in mammalian breast. As for other animals such as rabbits and swine, it can cause septicemia (3), which is a systematic inflammatory response to infections. This microorganism has also caused fibrinous pericarditis, fibrinous pleuritis, and pneumonia in sheeps. The overall symptoms of infections caused by S. zooepidemicus include lesions, pyrexia (fever), serous to mucopurulent nasal discharge, dyspnea (short of breath) (23).

Humans

In general, this pathogen rarely causes human infections (3, 4, 24). However, Streptococcus zooepidemicus has been reported to have caused a broad range of diseases, including septicemia and endocarditis (6), respiratory tract infection leading to nephritis (7), cervical lymphadenitis (8), septic arthritis and pneumonia (9), and meningitis (10, 11). Severe condition of these infections has caused deaths in some cases (9, 11, 18). In this one rare case, there is evidence of S. zooepidemicus involving in superantigen production, which contributed to the death of a 63-year-old man who died shortly after suffering from toxic shock-like syndrome (18).

Streptococcus zooepidemicus has also been reported to have caused poststreptococcal glomerulonephritis (PSGN), which is an acute inflammatory disorder of the glomerulus (24, 25). PSGN is usually developed in the aftermath of an acute throat or skin infection with a GAS strain; in this case, this disease caused by group C S. zooepidemicus was due to ingestion of food products made from unpasteurized milk. Interestingly, this disorder caused by subspecies zooepidemicus occurs predominantly in adults, whereas PSGN caused by GAS occurs in children (24, 25). Some of the clinical syndroms may include fever, edema, pharyngitis, hypertension, reduced renal function, and an increase in microalbuminuria (25, 26), a small amount of albumin present in urine.

Several theories have been proposed as an explanation for the initiation of PSGN; however, the main cause is still left undetermined (25). By activating the complement cascade via alternative pathway, PSGN causes glomerular inflammation by affecting the mesangial and endothelial cells. This activation will lead to an accumulation of fibrin in the glomeruli and a proliferation of parietal epithelial cells in Bowman’s capsule; it will also increase the entry of inflammatory cells, causing acute glomerular crescent formation. The glomerular capillaries will also be clogged due to the permeation of leukocyts and platelets. Along with the tissues being damaged and the filtration barrier of basement membrane being altered, these immune complexes may accumulate and fluid retention may occur, causing edema and vascular congestion (26).

Application to Biotechnology

Streptococcus zooepidemicus is used in bacterial fermentation for producing hyaluronic acid, which is a component that is widely used in ophthalmic surgery and as an ingredient in cosmetics (15). Derivatives of this mucopolysaccharide are used mainly as a source of skin filler for anti-aging and lip augmentation due to its ability to “form a gelatinous materials in the tissue space, acting as a lubricant and shock absorbent” (16, 17) and high water retention capacity (27). Hyaluronic acid has also been used in viscosurgery and as a lubricating supplement in arthritic joints.

Current Research

In the first study, scientists investigated in an unusual outbreak of mastitis in sheep produced by Streptococcus zooepidemicus; it was the first report of sheep mastitis associated with this microorganism. There were 170 crossbred Awassi-Rubia de El Molar sheep, living in conditions meeting the standards, detected with S. zooepidemicus infection in the mammary glands. Without any signs of illness, the ewes were producing watery milk secretion contaminated with pus. For 48 hours, the milk samples were incubated aerobically at 37° C, and the all of the clinical isolates were identified as S. zooepidemicus. The samples also showed a high excretion rate of this pathogen in the milk with counts ranging from 5.7 × 103 to 1.1 × 104 CFU/ml. As for treating future outbreaks, penicillin was advised to be used because of the high level of susceptibility shown in the clinical isolates. This mammary gland infection due to S. zooepidemicus was later named as pseudoagalactia, and it has become a major concern because S. zooepidemicus is capable of causing human infections and outbreaks associated with ingestion of unpasteurized milk products (22).

The second study was about a fatal case of toxic shock-like syndrome due to group C streptococci --- Streptococcus zooepidemicus. A 63-year-old man had a series of symptoms including a painful swelling left thigh, a skin rash on his truck and limbs, rigors, and a persistent fever of 39.5°C. An examination was given and the result showed that he had abnormally high levels of C-reactive protein (239 mg/liter), serum urea (12.8 mmol/liter), creatinine (194 μmol/liter), and lactate (9.2 mmol/liter). He also had high levels of creatine kinase (14,790 U/liter) and troponin (4.63 μg/liter). Other results have also shown that his liver function was abnormal with a high bilirubin level of 29 μmol/liter as compared to a normal range of <17 μmol/liter. Aside from those abnormalities, he also developed coagulopathy. The man was sent in for an operation and subcutaneous and muscle edema was determined. After the operation, his condition had gotten worse with a fever exceeding 40°C and a progressive multisystem organ failure, including failures of the circulatory and respiratory system, anuric renal failures, and liver dysfunction. With worsened coagulopathy, the outcome was fatal. By obtaining Streptococcus zooepidemicus isolates from muscle biopsies and knee joint fluid, the result of the patient’s isolate showed complete sequence homology with S. zooepidemicus. No known GAS superantigen exotoxin genes were found S. zooepidemicus; however, this case showed evidence of superantigen toxin production by this microorganism and studies should be done to further investigate “the role of superantigen exotoxins in the pathogenesis of invasive disease due to CGS” (18).

In the third study, three persons infected with Streptococcus zooepidemicus septicemia were admitted to the Tampere University Central Hospital (TaYS) in 2003. These three patients have all consumed fresh goat cheese. Specimens gathered include throat swabs, raw goat milk, cheese from unpasteurized milk, vaginal samples of goats, and well water. Additional nasal swab samples from goats were also taken. Cheese samples were incubated both aerobically and anaerobically at 37°C. Other samples, such as the vaginal and nasal swabs were also incubated anaerobically at 5% CO2 atmosphere with a temperature of 37°C. Through ribotyping and pulsed-field gel electrophoresis (PFGE), isolates of S. zooepidemicus were determined in the above specimens. Fortunately, there was no death resulting from infections ranging from septicemia to purulent arthritis, which are diseases that may be caused by S. zooepidemicus. Most of the patients were given pencillin for treatment, and some received penicillin along with aminoglycosides. People soon recovered and were discharged after 6-32 days. However, diseases associated with S. zooepidemicus may recur if unpasteurized milk products were consumed (4).

References

[1] DMSZ site DSMZ
[2] NCBI site NCBI Genome Project
[3] Bisno, Alan L. and Gaviria, J. Milton. "Group C and G Streptococci". Streptococcal Infections: Clinical Aspects, Microbiology, and Molecular Pathogenesis. New York: Oxford University Press, 2000.]
[4] Markku Kuusi, Elina Lahti, Anni Virolainen, Maija Hatakka, Risto Vuento, Leila Rantala, Jaana Vuopio-Varkila, Eija Seuna, Matti Karppelin, Marjaana Hakkinen, Johanna Takkinen, Veera Gindonis, Kyosti Siponen, and Kaisa Huotaru. "An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese". PubMed Central. 27 February 2006. 25 August 2007.
[5] Hans Lindmark, Martin Nilsson, and Bengt Guss. "Comparison of the Fibronectin-Binding Protein FNE from Streptococcus equi Subspecies equi with FNZ from S. equi Subspecies zooepidemicus Reveals a Major and Conserved Difference". PubMed Central. May 2001. 25 August 2007.
[6] Yuen KY, Seto WH, Choi CH, Ng W, Ho SW, and Chau PY. "Streptococcus zooepidemicus (Lancefield group C) septicaemia in Hong Kong". PubMed Central. Nov 1990. 25 August 2007.
[7] Barnham M, Thornton TJ, and Lange K. "Nephritis caused by Streptococcus zooepidemicus (Lancefield group C)". PubMed Central. 30 April 1983. 25 August 2007. [8] Kohler W and Cederberg A. "Streptococcus zooepidemicus (group C streptococci) as a cause of human infection". PubMed Central. 1976. 25 August 2007.
[9] Barnham M, Ljunggren A, and McIntyre M. "Human infection with Streptococcus zooepidemicus (Lancefield group C): three case reports". PubMed Central. April 1987. 26 August 2007.
[10] James Downar, Barbara M. Willey, Jeffrey W. Sutherland, Kelly Mathew, and Donald E. Low. "Streptococcal Meningitis Resulting from Contact with an Infected Horse". PubMed Central. June 2001. 27 August 2007.
[11] Edwards AT, Roulson M, and Ironside MJ. "A milk-borne outbreak of serious infection due to Streptococcus zooepidemicus (Lancefield Group C)". PubMed Central. August 1988. 25 August 2007.
[12] Jean-Pierre Lavoie, Lucie Couture, Robert Higgins, and Sheila Laverty. "Aerobic bacterial isolates in horses in a university hospital, 1986-1988". PubMed Central. May 1991. 26 August 2007.
[13] Mary Lou Nicholson, LaReesa Ferdinand, Jacquelyn S. Sampson, Andrea Benin, Sharon Balter, Sergio Wyton Lima Pinto, Scott F. Dowell, Richard R. Facklam, George M. Carlone, and Bernard Beall. "Analysis of Immunoreactivity to a Streptococcus equi subsp. zooepidemicus M-Like Protein To Confirm an Outbreak of Poststreptococcal Glomerulonephritis, and Sequences of M-Like Proteins from Isolates Obtained from Differet Host Species". PubMed Central. November 2000. 27 August 2007.
[14] Sanger Institute site: S. zooepidemicus
[15] Tan SW, Johns MR, and Greenfield PF. "Hyaluronic acid -- a versatile biopolymer". PubMed Central. January 1990. 27 August 2007.
[16] F. Manna, M. Dentin, P. Desider, O. De Pita, E. Mortilla, and B. Maras. "Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (Hylaform® from rooster combs and Restylane® from streptococcus) used for soft tissue augmentation". JEADV: Journal of the European Academy of Dermatology and Venereology. November 1999. 27 August 2007.
[17] ScienceWeek site "ScienceWeek"
[18] Tony M. Korman, Anthony Boers, Travis M. Gooding, Nigel Curtis, and Kumar Visvanathan. "Fatal Case of Toxic Shock-Like Syndrome Due to Group C Streptococcus Associated with Superantigen Exotoxin". Pub Med Central. June 2004. 25 August 2007.
[19] Balsamo, Gary A. "Antibacterial Agent Susceptibility and Resistance & Bacterial Anatomical Site Analysis". 28 August 2007.
[20] Richard M. Krause M.D. and Maclyn McCarty M.D. "Studies On the Chemical Structure of Streptococcal Cell Wall: I". JEM: The Journal of Experiment Medicine. 1961. 25 August 2007.
[21] NSGS site "Gram Positive, Spore-Forming Bacteria"
[22] Alfonso Las Heras, Ana I. Vela, Elena Fernandez, Emilio Legaz, Lucas Dominguez, and Jose F. Fernandez-Garayzabal. "Unusual Outbreak of Clinical Mastitis in Dairy Sheep Caused by Streptococcus equi subsp. zooepidemicus". PubMed Central. March 2002. 25 August 2007.
[23] Stevenson RG. "Streptococcus zooepidemicus infection in sheep". NCBI. July 1974. 26 August 2007.
[24] Markku Kuusi, Elina Lahti, Anni Virolainen, Maija Hatakka, Risto Vuento, Leila Rantala, Jaana Vuopio-Varkila, Eija Seuna, Matti Karppelin, Marjaana Hakkinen, Johanna Takkinen, Veera Gindonis, Kyosti Siponen, and Kaisa Huotaru. "An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese". BMC Infectious Disease. 27 February 2006. 27 August 2007.
[25] Ricardo Sesso and Sergio Wyton L. Pinto. "Five-year follow-up of patients with epidemic glomerulonephritis due to Streptococcus zooepidemicus". Oxford Journals. 2005. 27 August 2007.
[26] Benudiz, Natalie. "Recognizing the elusive signs and symptoms of PSGN". JAAPA: Journal of the American Academy of Physician Assistants. 27 August 2007.
[27] The Univeristy of Queensland site "Metabolic engineering of hyaluronic acid production"
[28] H D Rose, J R Allen, and G Witte. "Streptococcus zooepidemicus (group C) pneumonia in a human". PubMed Central. January 1980. 26 August 2007.
[29] Youichi Kuroiwa, Toru Anzai, Tohru Higuchi, and Takuo Sawada. "A PCR-RFLP Analysis of the Szp Gene in Streptococcus zooepidemicus Isolates from Mares with Metritis in Japan". 2006. 27 August 2007.
[30] Akesson, Maria, Dufour, Muriel, Sloan, Gary L., and Simmonds, Robin S. "Targeting of streptococci by zoocin A". IngentaConnect. May 2007. 27 August 2007.
[31] R. S. Simmonds, L. Pearson, R. C. Kennedy, and J. R. Tagg. "Mode of Action of a Lysostaphin-Like Bacteriolytic Agent Produced by Streptococcus zooepidemicus 4881". American Society for Microbiology. December 2006. 27 August 2007.
[32] Jinyu Zhang, Ning Hao, and Guo-Qiang Chen. "Effect of expressing polyhydroxybutyrate synthesis genes (phbCAB) in Streptococcus zooepidemicus on production of lactic acid and hyaluronic acid". SpringerLink. June 2006. 27 August 2007.
[33] Chong BF and Nielsen LK. "Amplifying the cellular reduction potential of Streptococcus zooepidemicus". PubMed Central. 9 January 2003. 27 August 2007.

Edited by Jenny Chong, student of Rachel Larsen

Edited by KLB