Integrin Beta-1: The Key to Porphyromonas Invasion

Let’s use the usual example: Porphyromonas gingivalis (PG).

PG is a classic opportunistic pathogen — more precisely a pathobiont — of the gingival pockets in periodontal disease, and it attacks the host’s cells partly through its fimbriae.

Bacterial fimbriae are thin, filament-like extensions found on the surface of many bacteria. These structures, visually similar to microscopic hairs, are fundamental to bacterial biology.

Fimbriae originate from the cytoplasmic membrane and measure between 0.2 and 2 µm in length. They are rigid, cylindrical structures built from a protein called pilin, which organises itself into helical arrangements.

At the free end of the fimbria sit a variable number of other proteins, the adhesins. Each has its own peculiar shape, complementary to structures on the cells of other living organisms: these adhesins are the mechanism by which the bacterium can stick to the host’s cells, and then invade them directly.

Colonisation and infection both run through this. In some cases the fimbriae also help bacteria move toward nutrients or escape harmful substances. In Porphyromonas gingivalis, the fimbriae let the pathobiont travel even inside cells it has already invaded, and slip from one cell to the next.

The point of attack — the Trojan horse — that lets the fimbriae of Porphyromonas gingivalis grab the host’s cells is integrin beta-1 (β1), on the cell surface.

Integrin beta-1, also known as CD29, is a cell-surface protein that governs the interactions between cells and the extracellular matrix (ECM). It belongs to the integrin family — heterodimers made of two subunits, one alpha and one beta. Integrin beta-1 can pair with several alpha subunits, forming integrin complexes that act as receptor-transmitters for various ECM components, such as collagen and fibronectin.

Integrins, beta-1 included, take part in several biological processes:

1) Cell adhesion: integrins anchor cells to the ECM, letting them hold their position and resist mechanical forces.

2) Signal transduction: when integrins bind to other ECM proteins, they pass biochemical signals into the cell. This regulates functions such as proliferation, migration and differentiation.

Sometimes that binding, and the signalling that follows, is the first step of a direct bacterial assault. That’s exactly what happens with PG: integrin beta-1 on the host cell surface recognises the adhesins on the fimbriae.

The transduction of that fimbrial signal then drives a rearrangement of the cytoskeleton whose purpose is to internalise the bacteria into the cytoplasm. So it is the host’s own eukaryotic cells that hand the bacterial aggressor the keys.

This logic makes obvious sense for immune cells — macrophages, say — that internalise invaders in order to neutralise them.

The same thing, though, happens with cells that have far weaker defences. PG invades the gingival epithelial cells (and not only those…) — a phenomenon I’ve also covered in how gum bacteria invade our cells — and inside them it stays alive and replicates.

For years this was a laboratory story. Then, in 2025, came the confirmation that closes the circle on integrin beta-1 itself. Huang and colleagues (Journal of Translational Medicine, 2025) isolated PG’s fimbrial protein FimA and watched it hook onto the CD151/integrin β1 (ITGB1) complex on the host membrane: from that grip a cytoskeletal rearrangement unfolds — through the JNK/paxillin pathway — identical in its logic to the one we’ve just described for the gingival cell. They saw it in carcinoma cells, where the bacterium promoted migration and metastasis. But the point isn’t oncology. The point is that the fimbria → integrin → internalisation mechanism works wherever PG finds the right lock.

The fimbriae, in any case, are not all alike. Alongside FimA, PG carries a second type, Mfa1, and disarming them pays off. Cao and colleagues (mSphere, 2024) built monoclonal antibodies against Mfa1 and, in an animal model of periodontitis, cut the bacterium’s adhesion to cells and — this is what counts — the loss of alveolar bone. Take the grappling hooks away from the bug, and much of the assault stalls. It’s the same logic that underpins how we treat severe periodontitis: break the chain of attack rather than chase its consequences.

There is a further chapter on the fimbriae that concerns macrophages, and it overturns the reassurance above. Wielento and colleagues (Journal of Oral Microbiology, 2026), from Potempa’s group in Kraków, exposed human monocyte-derived macrophages to wild-type and mutant PG strains, and to isolated fimbriae. Fimbriae modified by the enzyme PPAD — a peptidyl arginine deiminase that citrullinates proteins — switched on the macrophage’s inflammatory response, while fimbriae lacking the accessory subunits switched on nothing at all. That same modification protected the bacterium from being killed by the macrophage. Put plainly: the cell that ought to destroy it takes it in, inflames, and leaves it alive. The macrophage becomes a shelter.

Which raises the clinical question: if the bacterium is inside, does the antibiotic reach it? Barely, and that explains a good share of recurrences. Liu and colleagues (International Journal of Oral Science, 2026) tried the opposite route — instead of hitting the bacterium, shut the host’s doors. They blocked four host targets: collagen I, lipid rafts with simvastatin, the FAK pathway, and integrin β1 itself with the molecule ATN-161. Each block reduced infection in human oral keratinocytes and periodontal ligament stem cells; simvastatin gave the latter back the bone-forming capacity the infection had switched off. Then they added the antibiotic: simvastatin plus metronidazole cleared intracellular bacteria at reduced antibiotic doses, and in a rat model of periodontitis it cut bacterial load, inflammation and alveolar bone loss. This is preclinical work, in rats and in culture. But it points somewhere we cannot yet go chairside: make the cell an uncomfortable shelter, instead of chasing the bacterium with ever-higher doses.

Then there’s a chapter PG writes far from the mouth. Once inside, it doesn’t sit still: its most fearsome enzymes, the gingipains, are packaged and shipped out by a dedicated secretion system — the T9SS, reconstructed step by step by Lei and colleagues (Molecular Oral Microbiology, 2025) — and they also travel inside outer-membrane vesicles. These parcels are what let the bug spread its weapons at a distance. The review by Shawkatova and colleagues (Life, 2025) gathered the evidence that PG’s gingipains and LPS, once past the blood-brain barrier, feed the neuroinflammatory processes of Alzheimer’s disease. It remains an association, not a verdict. But it explains why a bacterium of the gums gets neurologists talking.

A caution about generalising, though, is in order. Ahmadi and colleagues (Journal of Oral Microbiology, 2026), in a narrative review from the University of Florida, lined up PG’s genetic variability: FimA and Mfa1 fimbriae, gingipains, haemagglutinins, capsule, lipopolysaccharide, the RagAB system, the T9SS. Differences between strains in the capacity to invade tissue and evade defences are marked, and they do not hang on a single gene. Carrying PG in your mouth and developing aggressive periodontitis remain two different things, and the strain is one of the variables that decide which of the two you get.

It all starts with something banal: colonisation. PG is transmitted — a kiss is enough — and it isn’t the only pathobiont that has learned to get inside our cells. Aggregatibacter actinomycetemcomitans plays the same game by different rules. The difference, as always in periodontal disease, comes down to balance: as long as the defences hold, the bacterium is just an awkward guest; when the balance breaks, it becomes an invader.

Image created with BioRender.com

References

1. Huang X, Zhuang Y, Wang R, et al. Colonization by Porphyromonas gingivalis in cervical squamous cell carcinomas promotes metastasis through FimA/CD151/ITGB1 signaling. J Transl Med. 2025;23(1):1166. doi:10.1186/s12967-025-06928-y · PMID: 41136985
2. Lei Z, Ma Q, Zhou X, Li Y. The secretion and maturation journey of gingipains. Mol Oral Microbiol. 2025;40(5):177-190. doi:10.1111/omi.12497 · PMID: 40490843
3. Cao M, Wang S, Zhou S, et al. Development of monoclonal antibodies against Mfa1 and their protective capacity in an experimental periodontitis model. mSphere. 2024;10(1):e0072124. doi:10.1128/msphere.00721-24 · PMID: 39699191
4. Shawkatova I, Durmanova V, Javor J. Alzheimer’s disease and Porphyromonas gingivalis: exploring the links. Life (Basel). 2025;15(1):96. doi:10.3390/life15010096 · PMID: 39860036
5. Liu X, Yuan Z, Wan Z, Yuan X, Wang Y, Gao Y, et al. P. gingivalis-host interactions direct antibiotic adjuvants for periodontitis antimicrobial therapy. Int J Oral Sci. 2026;18(1):50. doi:10.1038/s41368-026-00448-1 · PMID: 42425934 — preclinical: keratinocytes, periodontal ligament stem cells and a rat periodontitis model.
6. Wielento A, Drapała DM, Terekhova M, Jacuła A, Artyomov MN, Kochan J, et al. Macrophage activation and invasion by P. gingivalis is modulated by PPAD and accessory fimbriae subunits. J Oral Microbiol. 2026;18(1):2638646. doi:10.1080/20002297.2026.2638646 · PMID: 41788297 — citrullination of the accessory fimbrial subunits protects the bacterium from macrophage killing.
7. Ahmadi H, Burks J, Innamorati KA, Ehrlich GD, Progulske-Fox A. Virulence diversity among Porphyromonas gingivalis strains: a review of genetic factors. J Oral Microbiol. 2026;18(1):2701564. doi:10.1080/20002297.2026.2701564 · PMID: 42487771 — narrative review; virulence rests on several loci, not on a single determinant.