9.3 Type II and Type IV Secretion Atlas of Bacterial and Archaeal Cell Structure Home


This average of type II secretion systems from many Legionella pneumophila cells shows the overall structure: a channel through the cell envelope, gated near the outer membrane [79]. The pseudo-pilus can be seen in individual T2SSs, extending from the inner membrane to the bottom of the main channel. It gets washed out in the average, though, indicating that it is relatively flexible (i.e. not always in the same position). We still need to figure out exactly how the system works, including whether the pseudo-pilus does act like a piston, and how the gate opens.

Source: Ghosal et al. (2019) Structure: EMD-0566


This average of type IV secretion systems from many Legionella pneumophila cells shows the overall structure [80]. (You can watch an animation of the components on YouTube.) We do not yet know how secretion works, but one possibility is that effectors are transported either straight through the channel from the cytoplasm and/or first into the periplasm and from there into the windowed chamber just inside the outer membrane before finally being escorted out of the cell. Animation by Janet Iwasa.


This Helicobacter pylori cell was cultured together with human gastric epithelial cells, its target for infection. It contains inactive type IV secretion systems, as well as several mysterious tubes. The tubes are formed from the outer membrane, but we do not know what scaffolds them (they have a consistent diameter of 37 nm and a helical protein scaffold inside), or what makes the portals along their length. The fact that we sometimes see tubes near inactive T4SSs, and the fact that the tubes are missing from mutant cells lacking T4SS components suggests a relationship, but the details are unclear. Much remains mysterious about this structure and its potential role in infection.

Type II and Type IV Secretion

How else might your cell deal with the crowd? Well, if you can’t join them, maybe you should try to beat (and eat) them. Bacteria have evolved an impressive arsenal of molecular weaponry. In fact, most of the antibiotics we use were invented by bacteria. In many cases, cells simply release these antibiotics to the environment, either directly or in membrane vesicles, which may travel further. For more specific targeting, though, cells employ a varied array of secretion systems. You already saw some of these nanomachines in Chapter 6: a type III secretion system assembles the flagellum and a type II secretion system assembles the archaellum. Another type II secretion system makes (and unmakes) type IV pili. Other family members have evolved more militaristic functions.

Type II secretion systems (T2SSs) in Legionella pneumophila like this pump out effector proteins that enable a complex pathogenic lifecycle. L. pneumophila live in several environments: inside amoebae, outside cells (but sometimes with others in biofilms), and inside our cells, where they cause the severe pneumonia known as Legionnaires’ disease. In each environment, the T2SS pumps out proteins that facilitate growth there. For instance, once we inhale L. pneumophila with water droplets, they are internalized by our macrophages. They then use their T2SSs to secrete proteins that prevent their pockets in the cell (called Legionella-containing vacuoles) from being degraded, and suppress our innate immune response. This gives the bacteria time to replicate and establish a persistent colony. The T2SSs also secrete a toxin protein that breaks down lung tissue.

Unlike the secretion systems in Chapter 6, the T2SS does not build an extracellular appendage. Instead, it is thought to work by pumping proteins through the envelope channel using a short piston-like “pseudo-pilus” (⇩), pushing the molecules into the extracellular space. (Keep in mind that for these intracellular pathogens, their extracellular space is the interior of the host cell.)

L. pneumophila also use another, unrelated machine, a type IV secretion system (T4SS), to deliver more than 400(!) different kinds of effector proteins into host cells to promote infection. You can see multiple inactive T4SSs in this cell (⇩). We do not yet know what they look like during active secretion, so the mechanism remains unclear. In another human pathogen, Helicobacter pylori, inactive T4SSs are sometimes seen next to mysterious extracellular tubes, raising the intriguing possibility that the structures are somehow related (⇩).

This L. pneumophila cell is not unusual; it is common for pathogenic bacteria to employ multiple types of secretion systems. The bristling arsenal of bacteria is a fearsome thing.

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