Spirochetes and bacteria without a cell wall do not quite fit in with the classic con- cepts of bacteria that have been discussed so far. It is also a fact that there is no similarity between the members of the two groups; they are very different from each other. They are discussed here in one chapter only for the sake of brevity.
SPIROCHETES
Spirochetes are spiral, Gram-negative bacteria with a unique mode of motility that is quite different from those of other bacteria (they lack external flagella). All bacteria classified as spirochetes generally have a helical protoplasmic cylinder made of a thin layer of peptidoglycan and a multilayered outer membrane. Spirochetes differ considerably from each other with respect to habitats and physiological characteristics. Three genera are associated with serious diseases in humans. These are Treponema, Borrelia, and Leptospira.
Treponema pallidum
Disease
Treponema pallidum is the primary causal agent of syphilis, which is an important sexually transmitted disease and presents a global challenge. Approximately 30,000–40,000 persons are diagnosed with syphilis each year in the United States alone.
The three stages of syphilis
Primary: Characterized by formation of chancres (a localized lesion, about 1 cm in diameter) that usually develop at or near the site of the primary contact within 7–10 days. The lesion may heal spontaneously within 2–3 weeks.
Secondary: Secondary syphilis is characterized by diffuse rashes, including ones on the palms and soles, condyloma lata, and invasion of the central nervous system. Hepatitis and lymphadenopathy may also develop.
Tertiary: Tertiary stage develops after 1–3 years, in about 10%–20% of the untreated cases. Symptoms involving the central nervous system (CNS), cardiovas- cular system, and skin (gummas) may ensue, causing significant morbidity and mortality.
Lab Diagnosis
The causal agent, T. pallidum, cannot be cultured. Serological tests including ELISA and direct microscopic examination using dark field microscopy or fluorescence microscopy can be helpful. The bacterium appears as a thin spiral structure against a dark background (Fig. 11.1).
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| Figure 11.1. Electron micrograph of Treponema pallidum showing spiral filaments (source: CDC) |
Antibiotic Sensitivity
Most strains of T. pallidum are quite sensitive to penicillin. From the 1940s through the 1960s, the classic penicillin remained quite effective in the treatment of syphilis. However, penicillin-resistant strains have lately emerged, necessitating alternate therapeutic measures. Ceftriaxone and doxycycline can be used in primary and secondary disease cases, but penicillin still remains the drug of choice for the man- agement of tertiary disease.
Leptospira interrogans
The genus Leptospira is comprised of two species, L. interrogans and L. bifexa. Only members of L. interrogans are human pathogens. On the basis of their antigenicity, L. interrogans strains can be further divided into several serovars. However, less than a dozen serovars are associated with human diseases.
Disease
Leptospira interrogans cause leptospirosis, primarily a zoonotic disease. Several wild animals including mongooses, jackals, foxes, raccoons, bats, lizards, and rats are believed to be carriers. Domestic animals including dogs, goats, cattle, pigs, sheep, and horses are believed to contract leptospirosis from wild animals. Leptospirosis is often responsible for serious morbidity and mortality in domesticated animals. The spirochete is usually present in their urine. Humans acquire leptospirosis through direct contact with infected animals or via inhalation of their aerosolized urine or exposure to water contaminated with their fecal matters. Leptospira interrogans can survive in soil for up to 2 weeks and in water for several months. The usual portal of entry is the mucous membrane of the mouth, eyes, and genitals.
Leptospirosis can be mild and self-healing or acute and fulminating. The incubation period is generally 5–10 days and the organ systems most commonly involved are central nervous system, liver, and kidneys. Symptoms during the fulminating stage include high fever, occasionally rising to 105°F (41°C), severe headache, myalgia, and malaise, which may be accompanied by nausea and vomiting. Serious liver and kidney damage may ensue. The disease can occasionally be fatal if untreated.
Laboratory Diagnosis
The laboratory diagnosis of leptospirosis requires a careful consideration of the clinical phase of the infection. During early stages, most relevant clinical specimens are blood and cerebrospinal fluid, but urine must be examined if the samples are to be collected during the later phase. Tight characteristic spirals are easily seen under direct microscopic examination using dark field microscopy (Fig. 11.2). Leptospira interrogans is easily cultured on media fortified with rabbit serum or bovine serum albumin with Tween 80. Such media are commercially available in the United States
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| Figure 11.2. Electron micrograph of Leptospira interrogans. Note the spirals are tighter than those seen with T. pallidum (source: CDC). |
or can be made in the laboratory, if required. The incubation is done aerobically at 30°C for 10–15 days. Colonies of L. interrogans develop slowly and occasionally longer incubation period is required. Several serological tests including agglutina- tion test are also available and quite useful.
Antibiotic Sensitivity
Antibiotic therapy is not always indicated as the disase is often self-limited. Most of the pathological conditions are apparently due to a strong immune response. If required, tetracycline, penicillin, and cephalosporins are useful antibiotics for the management of leptospirosis.
Borrelia Species
The genus Borrelia has several species, of which nearly 15 are indicated in human diseases, B. burgdorferi being the best known and perhaps the most important. Borrelia infections are transmitted by arthropods; therefore it is classified as a zoonotic disease. Borrelia burgdorferi is the causal agent of Lyme disease, which is a tick-borne infection. Its natural habitat is the Ixodes tick that infests field mice and deer. Another species, B. recurrentis, causes relapsing fever and is transmitted to humans by a louse species, Pediculus humanus. Other Borrelia infections are also tick-borne and are mostly confined to specific geographic regions. For example, B. crocidurae and B. persica are considered causal agents of tick-borne relapsing fever in North Africa and Asia, respectively.
Disease
Cases of Lyme disease caused by B. burgdorferi have been reported from the Americas, Europe, Asia, and parts of Africa. One week following the tick bite, erythema (an elevated lesion), extending up to several centimeters in diameter, develops at the site of the bite. The infection spreads hematogenously, causing fever, headache, and neck pain. It can be fatal if not treated. About 10,000 cases are reported each year in the United States. The louse-born relapsing fever develops 2–15 days following the infection and is characterized by a sudden onset of fever, headache, and myalgia lasting for 5–10 days. The infection can be occasionally complicated by myocarditis. Borrelia burgdorferi and B. recurrentis produce toxins. Borrelia recurrentis strains are also known for antigenic shifts that are probably responsible for periodic febrile episodes.
Laboratory Diagnosis
Lyme disease is usually diagnosed on the basis of clinical symptoms and case history. Serological tests, though available, should be used only in conjunction with clinical and epidemiological data. Most strains grow well on Kelly’s modified medium, also known as Barbour-Stoenner-Kelly medium, under microaerophilic conditions. Inocu- lated media are generally incubated at 35°C for 7–14 days, occasionally longer.
Antibiotic Sensitivity
Tetracycline derivatives are usually preferred in the clinical management of Lyme disease but cephalosporins are indicated if the central nervous system is involved.
BACTERIA WITHOUT A CELL WALL
These are somewhat unusual bacteria in the sense that they lack a cell wall. Members of two genera, Mycoplasma and Ureaplasma, are important human pathogens.
Mycoplasma Species
Mycoplasma spp. are found in a wide range of niches including plants, arthropods, animals, and humans. Since they lack a cell wall, they do not have a regular shape, but most are approximately 0.1 µm in diameter. Instead, they maintain the stability of their cytoplasmic membrane with the help of sterols, which are obtained in the form of cholesterol from their animal hosts. Mycoplasma spp. have a small genome, consisting of 0.5–1.5 megabases; therefore they are often called “minimal cells.” There may be some dispute as to the exact number of species within the genus Mycoplasma, but four species are believed to be strongly associated with infections in humans. These are M. fermentans, M. genitalium, M. hominis, and M. pneumoniae.
Disease
Mycoplasma fermentans has been noted in the cases of pneumonia in otherwise healthy individuals. It is also believed to be a causal agent of nephropathy and certain forms of disseminated infection in patients primarily suffering from acquired immunodeficiency syndrome (AIDS). Strains identified as M. genitalium have been isolated from the human oropharynx and urethra and indicated in urethritis, pelvic inflammatory disease (PID), and even pneumonia-like symptoms. Mycoplasma hominis is often isolated from the urethra, cervix, and vagina and is believed to cause PID, pyelonephritis, and bacteremia. Instances of pneumonia and meningitis have also been noted in some cases. Of the four species, M. pneumoniae is perhaps the best known and most important pathogen. It is the major cause of pneumonia in children. The symptoms generally include mild fever, cough, and headache. It may account for almost 20% of all cases of pneumonia in children and the elderly. In addition, it is known to cause extrapulmonary infections including otitis and pharyngitis.
Virulence Factors
An important pathogenic trait of Mycoplasma spp. is their ability to adhere to the epithelial cells with the help of adherence proteins. One of the adherence proteins identified in the case of M. pneumoniae is a 168kD protein, which is found at the tip of the cell. In addition, hydrogen peroxide and superoxide, byproducts of mycoplasmal metabolism, also play a role in its pathogenesis.
Laboratory Diagnosis
Mycoplasma pneumoniae is a very slow-growing microorganism. Throat swabs or sputum are streaked on Mycoplasma agar. It must be noted that there is no single medium that is good for all clinically significant species of the genus Mycoplasma. Cultures take a long time to grow. ELISA and PCR are faster and more effective tools of laboratory diagnosis. Since a number of species belonging to the genus Mycoplasma can be isolated from clinical specimens, it may sometimes be necessary to differentiate them. Utilization pattern of glucose, arginine, and urea can be helpful. None of the clinically significant Mycoplasma spp. utilize urea (an important test for differentiating them from Ureaplasma). Mycoplasma pneumoniae and M. genitalium utilize glucose but not arginine. On the other hand, M. hominis utilizes arginine but not glucose while M. fermentans utilizes both. Another species, M. spermatophilum, can be isolated from urethra, but seems to have an uncertain etiologic role, and utilizes neither glucose nor arginine.
Antibiotic Sensitivity
Since mycoplasmas are devoid of a cell wall, antibiotics that target the bacterial cell wall are not indicated. Erythromycin and tetracycline derivatives are quite effective against M. pneumoniae and possibly other species.
Ureaplasma urealyticum
Like Mycoplasma spp., Ureaplasma spp. are devoid of a cell wall. Ureaplasma urealyticum can be isolated from the cervix and vagina of nearly 75% of sexually active females, especially those from lower socioeconomic strata and those with multiple sex partners. It is seldom isolated from the genitals of prepubescent girls who have had no sexual contact with males. Ureaplasma spp. have a genome of 0.75–1.2 Mbp and a GC content of 27–30%. Six species have been recognized within the genus, but only U. urealyticum is of major clinical significance.
Disease
Even though U. urealyticum is frequently isolated from female genitals, it is not known to cause any infection in women. Low vaginal pH is suspected to play a role in this unusual phenomenon. In contrast, U. urealyticum is believed to be the causal agent in nearly 40% cases of nongonococcal urethritis in males. Ureaplasma urealyticum is also an important causal agent of pneumonia and respiratory tract infections in newborn, mostly in infants with low birth weight.
Laboratory Diagnosis
Ureaplasma is a fastidious and slow-growing bacterium. It requires urea for its growth. Ureaplasma agar is a selective medium and culture is perhaps the most dependable tool for the diagnosis of Ureaplasma infections.
Antibiotic Sensitivity
Tetracyclines, macrolides, and fluoroquinolones are effective agents against U. urealyticum.
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