ProfessorJose Penades, FRS

José Penadés is a microbiologist specialising in the study of clinically significant bacteria and the mechanisms driving their evolution. His research has profoundly advanced our understanding of how bacteria acquire and disseminate genetic material, contributing to their adaptability and pathogenicity. Penadés’ work primarily focuses on the genetic and evolutionary dynamics of bacteria that pose significant threats to human health. Clinically relevant bacteria are those commonly associated with human infections, particularly those that exhibit antibiotic resistance or are involved in outbreaks. Understanding the evolution and acquisition of new traits in these bacteria is crucial for developing strategies to combat bacterial infections and curb antibiotic resistance.

Lateral transduction

A cornerstone of Penadés’ research is the role of bacteriophages (viruses that infect bacteria) and other mobile genetic elements (MGEs) in bacterial evolution. Bacteriophages play a key role in transferring genetic material between bacteria through processes like transduction. They can carry genes from one bacterium to another, spreading traits such as antibiotic resistance or virulence factors that enhance bacterial disease-causing capabilities. Penadés’ group is renowned for their deep insights into how bacteriophages mobilise bacterial chromosomal genes. One of Penadés' most significant discoveries is lateral transduction (1), a powerful mechanism of gene transfer facilitated by bacteriophages. This process allows bacteriophages to mobilise extensive segments of the bacterial chromosome, far beyond previously understood limits. This discovery challenges traditional views on bacterial DNA mobility, showing that entire regions of the chromosome can be transferred, greatly surpassing the mobility of classical mobile DNA elements like plasmids or transposons (2). Lateral transduction represents a major advancement in understanding how bacteria can rapidly acquire and disseminate new genes, particularly in the context of antibiotic resistance and the evolution of bacterial virulence.

Phage-inducible chromosomal islands (PICIs)

Penadés also identified and characterized Phage-Inducible Chromosomal Islands (PICIs), a widespread and clinically significant family of genetic elements found across diverse bacterial pathogens. PICIs are MGEs that can hijack bacteriophages to facilitate their own transfer between bacteria (3, 4). This discovery has profound implications for bacterial genetics and ecology (5), revealing a novel mechanism by which bacteria can acquire new genes and traits.

Lateral cotransduction

Building on the discovery of PICIs, Penadés’ lab uncovered a new gene transfer mechanism called lateral cotransduction (6). This process, related to but distinct from lateral transduction, involves the simultaneous transfer of multiple genetic elements, offering a more versatile means of gene mobility. Lateral cotransduction further elucidates the complex and dynamic ways bacteria exchange genetic material, adapt to new environments, evade immune responses, and develop antibiotic resistance.

Bacterial adaptation and virulence

In his research on the evolutionary pathways used by bacteria to infect different hosts, Penadés demonstrated that a single nucleotide mutation could profoundly alter host tropism (7). This finding revolutionised our understanding of the minimal genetic adaptations necessary for bacteria to cross species barriers and infect new hosts.

Arbitrium system

Recently, it has been discovered that bacteriophages exhibit social behaviors, including extracellular communication with their progeny through a peptide-based system known as arbitrium. The Penadés lab, in collaboration with the Marina group, is investigating the molecular basis of the arbitrium system across different MGEs (8, 9). Understanding these eco-evolutionary dynamics and the social interactions of MGEs could significantly impact our knowledge of virulence and resistance in clinically and agriculturally important bacterial species.

In summary, Penadés' pioneering work on bacteriophages (10), mobile genetic elements (11, 12), and novel gene transfer mechanisms (1, 6) has profoundly advanced our understanding of bacterial genetics and evolution. His discoveries may have crucial implications for public health and the treatment of infectious diseases.

References

1. Chen et al. 2018. Genome hypermobility by lateral transduction. Science 362:207–212.
2. Humphrey et al. 2021. Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements. Nature Communications 12:6509.
3. Tormo-Más et al. 2010. Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465:779–782.
4. Alqurainy et al. 2023. A widespread family of phage-inducible chromosomal islands only steals bacteriophage tails to spread in nature. Cell Host Microbe 31:69-82.e5.
5. Fillol-Salom et al. 2022. Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors. Cell 185:3248-3262.e20.
6. Chee et al. 2023. Dual pathogenicity island transfer by piggybacking lateral transduction. Cell 186:3414-3426.e16.
7. Viana et al. 2015. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nature Genetics 47:361–366.
8. Zamora-Caballero et al. 2024. Antagonistic interactions between phage and host factors control arbitrium lysis–lysogeny decision. Nature Microbiology 9:161–172.
9. Brady et al. 2023. Characterization of a unique repression system present in arbitrium phages of the SPbeta family. Cell Host Microbe 31:2023-2037.e8.
10. Rostøl et al. 2024. Bacteriophages avoid autoimmunity from cognate immune systems as an intrinsic part of their life cycles. Nature Microbiology 1–13.
11. Haag et al. 2021. A regulatory cascade controls Staphylococcus aureus pathogenicity island activation. Nature Microbiology 6:1300–1308.
12. Fillol-Salom et al. 2019. Hijacking the hijackers: Escherichia coli pathogenicity islands redirect helper phage packaging for their own benefit. Molecular cell 75:1020-1030.e4.