The Genus Corynebacterium

Chapter 8 The Genus Corynebacterium


Members of the genus Corynebacterium are actinomycetes that are related to the genera Mycobacterium, Nocardia, and Rhodococcus. The genus comprises aerobic gram-positive pleomorphic rods (Figure 8-1), often with a coccoid or club-shaped appearance, called diptheroidal after Corynebacterium diphtheriae, the agent of human diphtheria. Corynebacterium aquaticum is motile, but the remaining species in the genus are nonmotile. They are aerobic or facultatively anaerobic, catalase positive, non–spore forming and non–acid fast, with little tendency to branch. The cells walls of corynebacteria are singular in structure and composition; they are, in large part, the basis for the organism’s ability to survive under adverse environmental conditions, including the skin. They contain corynemycolic acids, which are granulomagenic and may mediate intracellular survival.



Corynebacterium diphtheriae and Corynebacterium ulcerans are prominent human pathogens. Arcanobacterium (Actinomyces, Corynebacterium) pyogenes, Actinobaculum (Actinomyces, Eubacterium, Corynebacterium) suis, and Arcanobacterium (Corynebacterium) haemolyticum are former members of the genus. The notable animal pathogens (Table 8-1) are Corynebacterium pseudotuberculosis, a cause of lymphadenitis and lymphangitis in small ruminants and horses, respectively, and Corynebacterium renale (cystitidis, pilosum), opportunist agents of urinary tract infections in cattle and occasionally other species. Corynebacterium pseudotuberculosis and C. ulcerans can produce diphtheria toxin when lysogenized by corynephage β-bearing tox.


TABLE 8-1 Corynebacteria Encountered in Veterinary Medicine






















































Corynebacterium Species Disease
C. diphtheriae Human diphtheria; bovine mastitis and dermatitis (infrequent); isolated from an equine wound infection
C. renale Bladder, kidney infections in cattle and swine; penis infections (pizzle rot) in castrated sheep; rare bladder infections in the dog; osteomyelitis in goats
C. cystitidis Bovine bladder and kidney infections
C. pilosum Bovine bladder and kidney infections
C. kutscheri Lung, lymph node, liver, kidney abscesses in rats, mice
C. pseudotuberculosis Ovine and caprine abscesses, lymphadenitis, abortion, arthritis; equine ulcerative lymphangitis, abscesses; bovine abscesses, mastitis (uncommon)
C. ulcerans Bovine mastitis, abscesses: gangrenous dermatitis in rodents
C. bovis Bovine mastitis (rare)
C. minutissimum “Skin scalding” syndrome (tail, brisket, interdigital space in lambs); rare cause of bovine mastitis
C. camporealensis Subclinical ovine mastitis
C. mastitidis Subclinical ovine mastitis
C. capitovis Isolated from skin scrapings of the infected head of a sheep
Group D2 Canine urinary tract infections
C. auriscanis Canine otitis, dermatitis, and vaginitis
C. amycolatum Bovine mastitis (rare)
C. testudinoris Necrotic mouth lesions in tortoises


DISEASES, EPIDEMIOLOGY, AND PATHOGENESIS


For many members of the genus there is little more information than that presented in Table 8-1, especially regarding pathogenesis.



Corynebacterium renale Group (C. renale, Corynebacterium pilosum, Corynebacterium cystitidis)


Corynebacterium renale is considered to be normal flora of the lower urogenital tract, and, based upon incidence of disease, is the most important member of the group. Corynebacterium pilosum is also normal flora, and is a less common cause of cystitis and, quite infrequently, pyelonephritis (Figure 8-2). Corynebacterium cystitidis is usually associated with chronic pyelonephritis, but can cause more severe cystitis than the other members of the group; isolation from normal animals is rare.



Thus members of the C. renale group are opportunistic pathogens of the urinary tract of cattle and other domestic animals. These organisms cause cystitis and ascending pyelonephritis, a sporadic but nonetheless widespread problem in cattle. Herd incidence greater than 5% is apparently uncommon, and is typically nearer 1%. Major risk factors are the shortness of the female urethra, effects of pregnancy and parturition, anatomic anomalies, physical damage, and obstruction of the urinary tract. Disease occurs most frequently in mature cows, and one quarter to one third of cases are fatal. Frequent relapses require additional treatment. Transmission may be venereal, but C. renale survives well in soil, possibly facilitating indirect transmission.


Colonization is pilus mediated, and the rapidly urease-positive nature of the organism leads to production of ammonia, with resulting mucosal inflammation. Cows with basic urine pH are at greater risk of developing pyelonephritis.


The clinical presentation of acute pyelonephritis includes fever, anorexia, polyuria, hematuria, pyuria, and abnormal posture (arched back). Infections that go untreated can become chronic, with weight loss, anorexia, and decreased milk production.


Posthitis (pizzle rot, sheath rot) is a form of preputial ulcerative dermatitis that occurs primarily in entire and castrated sheep and goats. The attack rate is rarely greater than 20%, and cases are often sporadic. The etiologic agents are C. pilosum and C. cystitidis, which are normal preputial inhabitants of these animals. Diets high in protein favor production of alkaline urine, with excretion of urea and production of ammonia by urease. This leads to ulceration of the preputial epithelium, with predisposition to secondary bacterial infections. Wethers grazing rich pastures are at risk, as are breeding rams and bucks on high-protein forages. Ewes may develop ulcerative vulvovaginitis after exposure to diseased rams at breeding.


Mild ulcers develop at the preputial orifice, often within 1 to 2 weeks of a dietary change. If left unattended, the lesions may spread into the preputial mucosa, with subsequent crusting, swelling, and pain. Painful urination may mimic urolithiasis. Pooled urine and purulent exudate inside the prepuce may lead to necrosis, development of sinus tracts draining through the prepuce to the skin, and, ultimately, to chronic scarring of the preputial orifice. Sequelae include fly-strike, occasional obstructive uremia, and, rarely, death.


The first step in pathogenesis of pyelonephritis is corynebacterial attachment to the urethral epithelium. Bacteria grow readily in urine, producing cystitis and ascending (through vesiculourethral reflux) to the kidney, where in most cases infection spreads chronically and relentlessly. Virulence factors of C. renale and their roles in pathogenesis have, except possibly of pili, not been explored in depth. Renalin, a C. renale extracellular protein with a strong nonenzymatic affinity for ceramide (one product of the action of phospholipase C on sphingomyelin), may play a role in lysis of cell membranes. This protein is apparently not produced by C. pilosum or C. cystitidis.


Pili are produced by all three of these species. Rare and apparently minor antigenic cross-reactions have been demonstrated between pili of C. renale and C. pilosum. Piliated organisms are more resistant to phagocytosis by mouseneutrophils in vitro than nonpiliated organisms (in the absence of opsonizing antibodies), but are phagocytosed at a rate equal to that of nonpiliated bacteria in the presence of antipilus serum and complement. Phagocytosis of piliated bacteria by mouse peritoneal macrophages is likewise enhanced by complement and by antipilus polyclonal serum. Curiously, polyclonal antibodies prepared against nonpiliated bacteria also enhance phagocytosis of piliated bacteria, suggesting that nonpilus factors may play an antiphagocytic role.


Loss of pili upon repeated in vitro passage in the presence of antipilus antibodies has been reported. In vivo growth of C. renale in mice is apparently also selective for nonpiliated organisms that are present as approximately 0.1% of piliated cultures. This selection is evidently not significantly influenced by growth in mice with naturally or passively acquired antipilus antibodies. Furthermore, in mice infected with C. renale, no significant differences in mortality, number of culture-positive mice, or numbers of bacteria recovered from the urinary tract have been found in mice infected with piliated and nonpiliated bacteria, suggesting that pili are not an obligate factor in virulence of C. renale or perhaps that the mouse is not an appropriate model of bovine infection.


The role of humoral and cellular immunity in these conditions has not been investigated thoroughly. Circulating antibodies are present in cows that develop pyelonephritis rather than cystitis, but humoral antibodies in mice immunized with killed organisms are apparently not protective because these mice develop pyelonephritis upon challenge. Data suggesting a selection for nonpiliated clones in mice may explain this lack of protection. In a rat model, IgG is apparently the major component of the immune response to C. renale infection.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on The Genus Corynebacterium

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