DrTiago Dias da Costa

The Costa Lab

The Costa Lab investigates how bacteria exchange genetic material, adapt to new environments, and evolve under selective pressures such as antibiotics. We are particularly interested in the molecular machines that drive horizontal gene transfer, phage-mediated gene flow, and antimicrobial resistance. By combining structural biology, cryo-electron microscopy, bacterial genetics, biochemistry, biophysics and AI-assisted discovery, we aim to understand these processes at atomic and mechanistic resolution.

A central question in our lab is how bacteria physically move DNA between cells. Our work has helped redefine how Type IV secretion systems, the molecular machines that mediate bacterial conjugation, assemble and function. We have shown that conjugative pili are not passive conduits, but dynamic structures that sense and respond to mechanical and environmental cues. These discoveries reveal how the physical properties of secretion systems influence DNA transfer, biofilm formation and the spread of antimicrobial resistance across bacterial communities.

We also study how phages and phage satellites shape bacterial evolution. Our recent work has shown that phage-inducible chromosomal islands can hijack structural components from unrelated phages to assemble chimeric, infectious particles capable of crossing species barriers. This revealed an unexpectedly efficient route for interspecies gene transfer, with important implications for the spread of virulence and antimicrobial resistance genes. These discoveries also provide the foundation for engineering phage satellites as programmable antibacterial and diagnostic platforms.

Another major focus of the lab is the integration of artificial intelligence into mechanistic microbiology. In collaboration with Google DeepMind, we demonstrated that AI systems can generate experimentally testable biological hypotheses that converge on mechanisms discovered through years of experimental work. This has helped establish the concept of an AI co-scientist and opened new possibilities for accelerating discovery in complex biological systems.

Together, our research asks a simple but fundamental question: how do bacteria and their mobile genetic elements build, control and exploit molecular machines to move DNA? By uncovering the atomic mechanisms that drive horizontal gene transfer, we aim to provide the molecular foundation for new strategies to combat antimicrobial resistance and engineer biological systems for therapeutic and diagnostic applications.

Selected Publications:

Paracuellos P, Bexter A, Patkowski JB, Kelly SD, Omelchenko O, Macé K, Ilangovan A, Subramoni S, Whitney JC, Filloux A, Costa TRD. Molecular basis of type VI secretion system effector loading. Nat Microbiol. 2026 May 27. doi: 10.1038/s41564-026-02363-x. Epub ahead of print. PMID: 42204345.

Gottweis J, Weng WH, Daryin A, Tu T, Sirkovic P, Myaskovsky A, Glowaty G, Weissenberger F, Orlandi A, Popovici D, Palepu A, Rong K, Tanno R, Saab K, Zhang F, Blum J, Carroll A, Kulkarni K, Tomašev N, Zverinski D, Rendulic I, Vedadi E, Hasler F, Rimanic L, Boia M, Budiselic I, Feinstein B, Bellaiche M, Sheffer T, Freyberg J, Ratcliff J, Bertolli O, Chou K, Hassidim A, Gokturk B, Vahdat A, Guan Y, Dhillon V, Vaishnav ED, Lee B, Costa TRD, Penadés JR, Peltz G, Matias Y, Manyika J, Hassabis D, Xu Y, Kohli P, Pawlosky A, Karthikesalingam A, Natarajan V. Accelerating scientific discovery with Co-Scientist. Nature. 2026 May 19. doi: 10.1038/s41586-026-10644-y. Epub ahead of print. PMID: 42156544.

Wong J, Refaat A, Villacampa-Teixeira P, Patkowski JB, Lapa N, Ortiz J, Dzierlega K, Roberts B, Tollenaar S, Croxen M, Thiesen A, Kao D, Willing B, Clemente-Casares X, Costa TRD, Elhenawy W. The assembly of a hybrid type IV secretion system by a Crohn's disease-associated Escherichia coli strain. Nat Commun. 2025 Oct 2;16(1):8797. doi: 10.1038/s41467-025-63859-4. PMID: 41038829.

He L, Patkowski JB, Wang J, Miguel-Romero L, Aylett CHS, Fillol-Salom A, Costa TRD, Penadés JR. Chimeric infective particles expand species boundaries in phage-inducible chromosomal island mobilization. Cell. 2025 Nov 13;188(23):6636-6653.e17. doi: 10.1016/j.cell.2025.08.019. Epub 2025 Sep 9. PMID: 40930093.

Penadés JR, Gottweis J, He L, Patkowski JB, Daryin A, Weng WH, Tu T, Palepu A, Myaskovsky A, Pawlosky A, Natarajan V, Karthikesalingam A, Costa TRD. AI mirrors experimental science to uncover a mechanism of gene transfer crucial to bacterial evolution. Cell. 2025 Nov 13;188(23):6654-6665.e2. doi: 10.1016/j.cell.2025.08.018. Epub 2025 Sep 9. PMID: 40930092.

Gahlot DK, Patkowski JB, Fernández de Santaella J, Allsopp LP, Pan Z, Filloux A, Larrouy-Maumus G, Francis MS, Costa TRD. Cpx-signalling in Yersinia pseudotuberculosis modulates Lipid-A remodelling and resistance to last-resort antimicrobials. NPJ Antimicrob Resist. 2024;2(1):39. doi: 10.1038/s44259-024-00059-y. Epub 2024 Nov 18. PMID: 39568730

Costa TRD, Patkowski JB, Macé K, Christie PJ, Waksman G. Structural and functional diversity of type IV secretion systems. Nat Rev Microbiol. 2024 Mar;22(3):170-185. doi: 10.1038/s41579-023-00974-3. Epub 2023 Oct 9. PMID: 37814112.

Patkowski JB, Dahlberg T, Amin H, Gahlot DK, Vijayrajratnam S, Vogel JP, Francis MS, Baker JL, Andersson M, Costa TRD. The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation. Nat Commun. 2023 Apr 5;14(1):1879. doi: 10.1038/s41467-023-37600-y. PMID: 37019921

Macé K, Vadakkepat AK, Redzej A, Lukoyanova N, Oomen C, Braun N, Ukleja M, Lu F, Costa TRD, Orlova EV, Baker D, Cong Q, Waksman G. Cryo-EM structure of a type IV secretion system. Nature. 2022 Jul;607(7917):191-196. doi: 10.1038/s41586-022-04859-y. Epub 2022 Jun 22. PMID: 35732732

Amin H, Ilangovan A, Costa TRD. Architecture of the outer-membrane core complex from a conjugative type IV secretion system. Nat Commun. 2021 Nov 25;12(1):6834. doi: 10.1038/s41467-021-27178-8.

Zheng W, Peña A, Ilangovan A, Baghshomali YN, Frankel G, Egelman EH, Costa TRD. Cryoelectron-microscopy structure of the enteropathogenic Escherichia coli type III secretion system EspA filament. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2022826118. doi: 10.1073/pnas.2022826118. PMID: 33397726

Sgro GG, Costa TRD, Cenens W, Souza DP, Cassago A, Coutinho de Oliveira L, Salinas RK, Portugal RV, Farah CS, Waksman G. Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri. Nat Microbiol. 2018 Dec;3(12):1429-1440. doi: 10.1038/s41564-018-0262-z. Epub 2018 Oct 22. PMID: 30349081

Costa TRD, Ilangovan A, Ukleja M, Redzej A, Santini JM, Smith TK, Egelman EH, Waksman G. Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein-Phospholipid Complex. Cell. 2016 Sep 8;166(6):1436-1444.e10. doi: 10.1016/j.cell.2016.08.025. PMID: 27610568

Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol. 2015 Jun;13(6):343-59. doi: 10.1038/nrmicro3456. PMID: 25978706.