Chlamydiae are obligate intracellular bacteria that cause a wide variety of diseases in humans and animals.
The chlamydiae were originally classified as four species in the genus Chlamydia: C. trachomatis, C. pneumoniae, C. psittaci, and C. pecorum (the last species being found in ruminants). The C. psittaci group has been separated into three species: C. psittaci, C. felis, and C. abortus. The mouse pneumonitis strain (MoPn) is now classified as C. muridarum, and the guinea pig inclusion conjunctivitis strain (GPIC) is now designated C. caviae.
C. trachomatis is divided into two biovars: trachoma and LGV (lymphogranuloma venereum). The trachoma biovar causes two major types of disease in humans: ocular trachoma, the leading infectious cause of preventable blindness in the developing world; and urogenital infections, which are sexually or neonatally transmitted. The 18 serovars of C. trachomatis fall into three groups: the trachoma serovars A, B, Ba, and C; the oculogenital serovars D–K; and the LGV serovars L1–L3. Serovars can be distinguished by serologic typing with monoclonal antibodies or by molecular gene typing. However, serovar identification usually is not important clinically, since the antibiotic susceptibility pattern is the same for all three groups. The one exception applies when LGV is suspected on clinical grounds; in this situation, serovar determination is important because a longer treatment duration is required for LGV strains.
During their intracellular growth, chlamydiae produce characteristic intracytoplasmic inclusions that can be visualized by direct fluorescent antibody (DFA) or Giemsa staining of infected clinical material, such as conjunctival scrapings or cervical or urethral epithelial cells. Chlamydiae are nonmotile, gram-negative, obligate intracellular bacteria that replicate within the cytoplasm of host cells, forming the characteristic membrane-bound inclusions that are the basis for some diagnostic tests. Originally considered to be large viruses, chlamydiae differ from viruses in possessing RNA and DNA as well as a cell wall that is quite similar in structure to the cell wall of typical gram-negative bacteria. However, chlamydiae lack peptidoglycan; their structural integrity depends on disulfide binding of outer-membrane proteins.
Among the defining characteristics of chlamydiae is a unique growth cycle that involves alternation between two highly specialized morphologic forms (Figs. 176-1 and 176-2): the elementary body (EB), which is the infectious form and is specifically adapted for extracellular survival, and the metabolically active and replicating reticulate body (RB), which is not infectious, is adapted for an intracellular environment, and does not survive well outside the host cell. The biphasic growth cycle begins with attachment of the EB (diameter, 0.25–0.35 μm) at specific sites on the surface of the host cell. The EB enters the cell through a process similar to receptor-mediated endocytosis and resides in an inclusion, where the entire growth cycle is completed. The chlamydiae prevent phagosome-lysosome fusion. The inclusion membrane is modified by insertion of chlamydial antigens. Once the EB has entered the cell, it reorganizes into an RB, which is larger (0.5–1 μm) and contains more RNA. After ∼8 h, the RB starts to divide by binary fission. The intracytoplasmic, membrane-bound inclusion body containing the RBs increases in size as the RBs multiply. Approximately 18–24 h after infection of the cell, these RBs begin to become EBs by a reorganization or condensation process that is poorly understood. After rupture of the inclusion body, the EBs are released to initiate another cycle of infection.
Chlamydial intracellular inclusions filled with smaller dense elementary bodies and larger reticulate bodies. [Reprinted with permission from WE Stamm: Chlamydial infections, in Harrison—s Principles of Internal Medicine, 17th ed, AS Fauci et al (eds). New York, McGraw-Hill, 2008, p 1070.]
Chlamydial life cycle. EBs, elementary bodies; RBs, reticulate bodies; IFN-γ, interferon γ. [Reprinted with permission from WE Stamm: Chlamydial infections, in Harrison—s Principles of Internal Medicine, 17th ed, AS Fauci et al (eds). New York, McGraw-Hill, 2008, p 1071.]
Chlamydiae are susceptible to many broad-spectrum antibiotics and possess a number of enzymes, but they have a very restricted metabolic capacity. None of these metabolic reactions results in the production of energy. Chlamydiae have thus been considered to be energy parasites that use the ATP produced by the host cell for their own metabolic functions. Many aspects of chlamydial molecular biology are not well understood, but the sequencing of several chlamydial genomes and new proteomics research have provided researchers with many relevant tools for elucidating the biology of the life cycle.
Genital infections are mostly caused by C. trachomatis serovars D–K, with serovars D, E, and F involved most often. Molecular typing of the major outer-membrane protein gene (omp1) from which serovar differences arise has been used to demonstrate that polymorphisms can occur in isolates from patients who are exposed frequently to multiple infections, while less variation is observed in isolates from less sexually active populations. Polymorphisms in the major outer-membrane protein may provide antigenic variation, and the different forms allow persistence in the community because immunity to one is not protective against the others.
The trachoma biovar is essentially a parasite of squamocolumnar epithelial cells; the LGV biovar is more invasive and involves lymphoid cells. As is typical of chlamydiae, C. trachomatis strains are capable of causing chronic, clinically inapparent, asymptomatic infections. Because the duration of the chlamydial growth cycle is ∼48–72 h, the incubation period of sexually transmitted chlamydial infections is relatively long—generally 1–3 weeks. C. trachomatis causes cell death as a result of its replicative cycle and can induce cell damage whenever it persists. However, few toxic effects are demonstrated, and cell death because of chlamydial replication is not ...