José R Penadés

José R Penadés
Imperial College London | Imperial · Department of Infectious Disease Epidemiology

DVM, PhD

About

218
Publications
41,794
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
9,753
Citations
Additional affiliations
March 2009 - December 2013
Instituto de Biomedicina
Position
  • Senior Researcher
March 2004 - February 2009
Valencian Institute for Agricultural Research
Position
  • Senior Researcher

Publications

Publications (218)
Article
Full-text available
The arbitrium system is employed by phages of the SPbeta family to communicate with their progeny during infection to decide either to follow the lytic or the lysogenic cycle. The system is controlled by a peptide, AimP, that binds to the regulator AimR, inhibiting its DNA-binding activity and expression of aimX. Although the structure of AimR has...
Article
Full-text available
In bacteria, adaptation to changes in the environment is mainly controlled through two-component signal transduction systems (TCSs). Most bacteria contain dozens of TCSs, each of them responsible for sensing a different range of signals and controlling the expression of a repertoire of target genes (regulon). Frequently, TCS control key physiologic...
Article
Full-text available
Staphylococcal pathogenicity islands (SaPIs) are mobile genetic elements encoding superantigens and other toxinsand are induced for excision, replication, packaging and intercell transfer by phage-encoded anti-repressors that counter the SaPI master repressor. Though SaPI induction has heretofore been assumed to be the exclusive province of helper...
Article
Full-text available
Phage-inducible chromosomal islands (PICIs) are a widespread family of highly mobile genetic elements that disseminate virulence and toxin genes among bacterial populations. Since their life cycle involves induction by helper phages, they are important players in phage evolution and ecology. PICIs can interfere with the lifecycle of their helper ph...
Article
Full-text available
Lysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with early prophage e xcision followed by DNA r eplication and p ackaging (ERP). This temporal program is considered universal for P22-like temperate phages, though there is no direct evidence to support the timing and...
Article
Full-text available
It is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus , where temperate phages can drive the transfer of la...
Article
Full-text available
Staphylococcus aureus pathogenicity islands (SaPIs) are molecular parasites that hijack helper phages for their transfer. SaPIbov5, the prototypical member of a family of cos type SaPIs, redirects the assembly of ϕ12 helper capsids from prolate to isometric. This size and shape shift is dependent on the SaPIbov5-encoded protein Ccm, a homolog of th...
Article
Full-text available
Conjugation has classically been considered the main mechanism driving plasmid transfer in nature. Yet bacteria frequently carry so-called non-transmissible plasmids, raising questions about how these plasmids spread. Interestingly, the size of many mobilisable and non-transmissible plasmids coincides with the average size of phages (~40 kb) or tha...
Article
Full-text available
Staphylococcal pathogenicity islands (SaPIs) are a family of closely related mobile chromosomal islands that encode and disseminate the superantigen toxins, toxic shock syndrome toxin 1 and superantigen enterotoxin B (SEB). They are regulated by master repressors, which are counteracted by helper phage–encoded proteins, thereby inducing their excis...
Article
Full-text available
Temperate bacteriophages (phages) are viruses of bacteria. Upon infection of a susceptible host, a temperate phage can establish either a lytic cycle that kills the host or a lysogenic cycle as a stable prophage. The life cycle pursued by an infecting temperate phage can have a significant impact not only on the individual host bacterium at the cel...
Preprint
Mobile genetic elements (MGEs) control their life cycles by the expression of a master repressor, whose function must be disabled to allow the spread of these elements in nature. Here we describe an unprecedented repression-derepression mechanism involved in the transfer of the Staphylococcus aureus pathogenicity islands (SaPIs). Contrary to the cl...
Article
Full-text available
Some Bacillus-infecting bacteriophages use a peptide-based communication system, termed arbitrium, to coordinate the lysis-lysogeny decision. In this system, the phage produces AimP peptide during the lytic cycle. Once internalized by the host cell, AimP binds to the transcription factor AimR, reducing aimX expression and promoting lysogeny. Althou...
Preprint
Full-text available
Lysogenic induction ends the stable association between a bacteriophage and its host, and the transition to the lytic cycle begins with prophage e xcision followed by DNA r eplication and p ackaging (ERP) – a temporal program that is considered universal for most temperate phages. Here we report that the long-standing ERP program is an artefact of...
Article
Full-text available
The emergence of new pathogens is a major threat to public and veterinary health. Changes in bacterial habitat such as a switch in host or disease tropism are typically accompanied by genetic diversification. Staphylococcus aureus is a multi-host bacterial species associated with human and livestock infections. A microaerophilic subspecies, Staphyl...
Article
Full-text available
Infections caused by Staphylococcus aureus pose a serious and sometimes fatal health issue. With the aim of exploring a novel therapeutic approach, we chose GraXRS, a Two-Component System (TCS) that determines bacterial resilience against host innate immune barriers, as an alternative target to disarm S. aureus. Following a drug repurposing methodo...
Preprint
Full-text available
Background The emergence of new bacterial pathogens represents a major threat to public and veterinary health. Staphylococcus aureus is a multi-host bacterial species comprising pathogenic clones with distinct tropisms for human and livestock species. A S. aureus microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius , is responsible f...
Article
Full-text available
Bacteria are able to sense environmental conditions and respond accordingly. Their sensorial system relies on pairs of sensory and regulatory proteins, known as two-component systems (TCSs). The majority of bacteria contain dozens of TCSs, each of them responsible for sensing and responding to a different range of signals. Traditionally, the functi...
Article
Phage satellites are genetic elements that depend on helper phages for induction, packaging and transfer. To promote their lifestyles, they have evolved elegant and sophisticated strategies to inhibit phage reproduction, which will be reviewed here. We will principally focus on the convergent interference mechanisms used by phage-inducible chromoso...
Article
Full-text available
The emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. Here we report the development of a series of CRISPR-Cas13a-based antibacterial nucleocapsids, termed Cap-sidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escheri...
Article
Full-text available
Commons Attribution License (CC BY 4.0). Phage-inducible chromosomal islands (PICIs) are a widespread family of mobile genetic elements, which have an important role in bacterial pathogenesis. These elements mobilize among bacterial species at extremely high frequencies, representing an attractive tool for the delivery of synthetic genes. However,...
Article
Full-text available
While many bacterial pathogens are restricted to single host species, some have the capacity to undergo host switches, leading to the emergence of new clones that are a threat to human and animal health. However, the bacterial traits that underpin a multihost ecology are not well understood. Following transmission to a new host, bacterial populatio...
Preprint
Full-text available
Emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. We established a series of CRISPR-Cas13a-based antimicrobials, termed PhagoCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant St...
Article
Full-text available
Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure t...
Article
Full-text available
Temperate phages are bacterial viruses that as part of their life cycle reside in the bacterial genome as prophages. They are found in many species including most clinical strains of the human pathogens, Staphylococcus aureus and Salmonella enterica serovar Typhimurium. Previously, temperate phages were considered as only bacterial predators, but m...
Article
Full-text available
Staphylococcus aureus is a mammalian commensal and opportunistic pathogen that colonizes niches such as skin, nares and diverse mucosal membranes of about 20-30% of the human population. S. aureus can cause a wide spectrum of diseases in humans and both methicillin-sensitive and methicillin-resistant strains are common causes of nosocomial- and com...
Presentation
Staphylococcus aureus subsp. anaerobius is a microaerophilic, catalase-negative bacterium responsible for abscess pathology (Morel’s disease) in small ruminants. We performed whole-genome sequencing to a collection of isolates taken in Europe and Africa over the last 30 years, and carried out an evolutionary genomic analysis to understand the molec...
Article
Full-text available
Bacillus phages use a communication system, termed “arbitrium,” to coordinate lysis-lysogeny decisions. Arbitrium communication is mediated by the production and secretion of a hexapeptide (AimP) during lytic cycle. Once internalized, AimP reduces the expression of the negative regulator of lysogeny, AimX, by binding to the transcription factor, Ai...
Article
Phage-inducible chromosomal islands (PICIs) represent a novel and universal class of mobile genetic elements, which have broad impact on bacterial virulence. In spite of their relevance, how the Gram-negative PICIs hijack the phage machinery for their own specific packaging and how they block phage reproduction remains to be determined. Using genet...
Article
Many staphylococcal bacteriophages encode a minor capsid protein between the genes for the portal and scaffolding proteins. In Staphylococcus aureus bacteriophage 80α, this protein, called gp44, is essential for the production of viable phage, but dispensable for the phage-mediated mobilization of S. aureus pathogenicity islands. We show here that...
Article
Genetic transduction is a major evolutionary force that underlies bacterial adaptation. Here we report that the temperate bacteriophages of Staphylococcus aureus engage in a distinct form of transduction we term lateral transduction. Staphylococcal prophages do not follow the previously described excision-replication-packaging pathway but instead e...
Article
Full-text available
Staphylococcus aureus is a major opportunistic pathogen that commonly forms biofilms on various biotic and abiotic surfaces. Also, most isolates are known to carry prophages in their genomes. With this in mind, it seems that acquiring a better knowledge of the impact of prophages on the physiology of S. aureus biofilm cells would be useful for deve...
Article
Full-text available
Phage-inducible chromosomal islands (PICIs) are a recently discovered family of pathogenicity islands that contribute substantively to horizontal gene transfer, host adaptation and virulence in Gram-positive cocci. Here we report that similar elements also occur widely in Gram-negative bacteria. As with the PICIs from Gram-positive cocci, their uni...
Article
Full-text available
Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. The core genome of the major human pathogen Staphylococcus aureus encodes 16 TCSs, one of which (WalRK) is essential. Here we show that S. aureus can be deprived of its complete sensorial TCS network and still survive under growth arrest conditions similarly to...
Conference Paper
Staphylocccus aureus is a major human and animal pathogen. Most strains infect a single host species, but transmission between humans and livestock are increasingly being reported, representing a threat to public health. These episodes may lead to pathogen host-adaptive changes that result in successful host-switches, but the underlying molecular m...
Article
Full-text available
The trimeric staphylococcal phage-encoded dUTPases (Duts) are signalling molecules that induce the cycle of some Staphylococcal pathogenicity islands (SaPIs) by binding to the SaPI-encoded Stl repressor. To perform this regulatory role, these Duts require an extra motif VI, as well as the Dut conserved motifs IV and V. While the apo form of Dut is...
Article
Full-text available
Author summary Understanding bacterial horizontal gene transfer is vital for establishing how toxins and antibiotic resistance genes are disseminated. Bacteriophage and pathogenicity islands make up key components of the wider horizontal transfer map. SaPIs are clinically relevant pathogenicity islands, residing passively in the host chromosome und...
Data
IC50 calculation of ϕDI-Stl complex formation inhibition by dUPNPP. (PDF)
Data
Oligonucleotide designs used in this study. (PDF)
Data
Plasmids used in this study. (PDF)
Data
ϕDI Dut represents a reduced version of dimeric Duts. (PDF)
Data
Dimeric Dut mutants do not induce the SaPI cycle. (PDF)
Data
Staphylococcal phage dimeric Duts identified by protein BLAST. (PDF)
Data
Evaluation of the molar ration in dimeric Dut-Stl interaction. (PDF)
Data
ϕDI Dut in complex with dUPNPP shows a closed conformation. (PDF)
Data
Overlay of ϕDI and T. cruzi dimer interfaces. (PDF)
Data
Differences in catalytic motifs between trimeric and dimeric Duts. (PDF)
Data
Bacterial strains used in this study. (PDF)
Data
The A73L mutation in ϕDI Dut prevents dUTP binding. (PDF)
Article
Full-text available
Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaP...
Data
β-lactamase assay data and statistical analysis for the dimeric ΦO11 Dut.
Data
β-lactamase assay data and statistical analysis for the recombinases.
Data
(A) Phage-inducible chromosomal islands analysed in this study. (B) Description and relationships between the PICI-encoded Stl repressorsa.