Chlamydia Cell Wall: Structure and Function

Chlamydia, a genus of obligate intracellular bacteria, is responsible for significant human diseases. The chlamydial cell wall is a unique structure, as its envelope deviates from typical bacterial models that provide structural integrity and protection.

The Peptidoglycan Anomaly in Chlamydia

For many years, the “chlamydial anomaly” puzzled microbiologists. This refers to the paradox that Chlamydia is susceptible to penicillin, an antibiotic that targets the synthesis of peptidoglycan (PG), yet a conventional PG layer could not be detected in its cell wall. Peptidoglycan is a polymer that forms a mesh-like layer, providing most bacteria with the structural strength to resist osmotic pressure. The absence of this layer, despite the presence of genes for its synthesis, created a long-standing debate.

Modern research has clarified this puzzle. Evidence suggests that Chlamydia possesses a modified and transient form of peptidoglycan. This PG is not a continuous, rigid sacculus but appears to be localized at the septum, the plane of cell division, during the bacterium’s replicative phase. It is less cross-linked and present only when and where it is needed for division.

The discovery of genes encoding elements for PG synthesis, such as PBP2 and PBP3, supports this conclusion. Although Chlamydia lacks FtsZ, a protein that directs septal division in most bacteria, it utilizes other proteins like MreB and RodZ to guide PG synthesis to the division site. This localized use of peptidoglycan explains its elusiveness and resolves the paradox of penicillin’s effectiveness.

Key Structural Components of the Chlamydial Envelope

The chlamydial cell envelope is a complex structure with a Gram-negative-like organization of an inner and outer membrane, but its molecular makeup is distinct. The outer membrane is important for the bacterium’s survival and interaction with host cells.

A dominant feature of the outer membrane is the Major Outer Membrane Protein (MOMP). This protein is abundant and functions as a porin, forming channels that allow the passage of small molecules and ions across the membrane. MOMP is also a primary antigen, a major target for the host immune response. Alongside MOMP are Polymorphic Outer Membrane Proteins (POMPs), which also reside on the surface and are implicated in binding to host cell receptors.

The outer membrane also contains lipopolysaccharide (LPS), which contributes to the endotoxic activity of the bacterium and stimulates the host’s immune system. However, chlamydial LPS is structurally different from that of many other Gram-negative bacteria, featuring a less toxic variant of its lipid A component. Another defining feature is the presence of Cysteine-Rich Proteins (CRPs) like OmcA and OmcB. These proteins are heavily cross-linked through disulfide bonds, creating a rigid network that provides structural stability.

Cell Wall Adaptations During the Chlamydial Developmental Cycle

The chlamydial cell wall is not static; it undergoes transformations to accommodate a biphasic developmental cycle. This cycle alternates between two distinct forms: the infectious Elementary Body (EB) and the replicative Reticulate Body (RB). Each form possesses a cell wall adapted to its function.

The Elementary Body is the small, dense, and infectious form that can survive outside of a host cell. Its cell wall is rigid and osmotically stable due to the extensive disulfide cross-linking of its Cysteine-Rich Proteins (CRPs). This robust structure protects the metabolically less active EB from environmental stresses.

Once inside a host cell, the EB differentiates into the Reticulate Body. The RB is larger, metabolically active, and replicates through binary fission. Its cell wall becomes more fragile and pliable, with a reduction in the disulfide cross-linking of its CRPs. This flexible state facilitates the uptake of nutrients from the host cell and division within an intracellular vacuole known as an inclusion. The cycle concludes when RBs reorganize and condense back into EBs, which are then released to infect new cells.

Role of the Cell Wall in Host Cell Interaction and Pathogenesis

The components of the chlamydial cell wall are central to how the bacterium interacts with host cells and causes disease. The process of infection begins when proteins on the surface of the EB, such as the Polymorphic Outer Membrane Proteins and potentially MOMP, act as adhesins that bind to specific receptors on host epithelial cells.

This binding initiates the bacterium’s entry into the cell, where it resides and replicates within a specialized vacuole called an inclusion. The bacterium modifies this inclusion by inserting its own proteins, known as Incs, into the inclusion membrane. These proteins help mediate interactions between the bacterium and the host cell’s cytoplasm, securing nutrients and avoiding defense mechanisms, like fusion with lysosomes.

Cell wall components are potent triggers of the host immune system. Molecules like LPS and MOMP are recognized by the host’s Toll-like receptors, leading to the production of cytokines and initiating an inflammatory response. While this response is designed to clear the infection, it is also responsible for much of the tissue damage associated with chlamydial diseases. The unique structure of the chlamydial cell wall, including its modified LPS and the antigenic variation seen in MOMP, may represent strategies for evading complete immune clearance.