Transfer of antibiotic resistance in Staphylococcus aureus

Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic elements and occurs primarily by conjugation or bacteriophage transduction, with the latter traditionally being perceived as the primary route. Recent work on conjugation and transduction suggests that transfer by these mechanisms may be more extensive than previously thought, in terms of the range of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen

Deciphering the molecular mechanism underpinning phage arbitrium communication systems

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, AimR, promoting lysogeny. We have elucidated the crystal structures of AimR from the Bacillus subtilis SPbeta phage in its apo form, bound to its DNA operator and in complex with AimP. AimR presents intrinsic plasticity, sharing structural features with the RRNPP quorum-sensing family. Remarkably, AimR binds to an unusual operator with a long spacer that interacts nonspecifically with the receptor TPR domain, while the HTH domain canonically recognizes two inverted repeats. AimP stabilizes a compact conformation of AimR that approximates the DNA-recognition helices, preventing AimR binding to the aimX promoter region. Our results establish the molecular basis of the arbitrium communication system

Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells

Prophages are quiescent viruses located in the chromosomes of bacteria. In the human pathogen, Staphylococcus aureus, prophages are omnipresent and are believed to be responsible for the spread of some antibiotic resistance genes. Here we demonstrate that release of phages from a subpopulation of S. aureus cells enables the intact, prophage-containing population to acquire beneficial genes from competing, phage-susceptible strains present in the same environment. Phage infection kills competitor cells and bits of their DNA are occasionally captured in viral transducing particles. Return of such particles to the prophagecontaining population can drive the transfer of genes encoding potentially useful traits such as antibiotic resistance. This process, which can be viewed as ‘auto-transduction’, allows S. aureus to efficiently acquire antibiotic resistance both in vitro and in an in vivo virulence model (wax moth larvae) and enables it to proliferate under strong antibiotic selection pressure. Our results may help to explain the rapid exchange of antibiotic resistance genes observed in S. aureus

Phage-inducible chromosomal islands promote genetic variability by blocking phage reproduction and protecting transductants from phage lysis

Funding: This work was supported by the following grants awarded to JPR: MR/M003876/1, MR/S00940X/1 and MR/V000772/1 from the Medical Research Council (MRC, UK; https://mrc.ukri.org); BB/N002873/1, BB/S003835/1 and BB/V002376/1 from the Biotechnology and Biological Sciences Research Council (BBSRC, UK; https://bbsrc.ukri.org); 201531/Z/16/Z from the Wellcome Trust (https://wellcome.org).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 phages at different stages resulting frequently in reduced phage production after infection of a PICI-containing strain. Since phage defense systems have been recently shown to be beneficial for the acquisition of exogenous DNA via horizontal gene transfer, we hypothesized that PICIs could provide a similar benefit to their hosts and tested the impact of PICIs in recipient strains on host cell viability, phage propagation and transfer of genetic material. Here we report an important role for PICIs in bacterial evolution by promoting the survival of phage-mediated transductants of chromosomal or plasmid DNA. The presence of PICIs generates favorable conditions for population diversification and the inheritance of genetic material being transferred, such as antibiotic resistance and virulence genes. Our results show that by interfering with phage reproduction, PICIs can protect the bacterial population from phage attack, increasing the overall survival of the bacterial population as well as the transduced cells. Moreover, our results also demonstrate that PICIs reduce the frequency of lysogenization after temperate phage infection, creating a more genetically diverse bacterial population with increased bet-hedging opportunities to adapt to new niches. In summary, our results identify a new role for the PICIs and highlight them as important drivers of bacterial evolution.Publisher PDFPeer reviewe

Screening of virulence genes in Staphylococcus aureus isolates from rabbits

Staphylococcus aureus is a versatile pathogen that can survive in diverse host environments and produce a wide range of diseases both in humans and animals. This versatility depends on its ability to modulate gene expression and the synthesis of virulence determinants. Therefore, this study aimed to investigate the distribution of bacterial virulence determinants in the most prevalent S. aureus strain types causing lesions in rabbits. Sixty-nine S. aureus strains were isolated from rabbit does with different chronic purulent lesions from 30 Spanish industrial rabbitries. Genotyping characterization of the strains was performed based on the analysis of the polymorphic regions of the coa, spa and clfB genes, as well as Multylocus Sequence Typing (MLST) on one strain of each of the most frequent genotypes. The isolates were also analyzed for the presence of forty virulence genes by PCRs and Southern blot, in order to determine their relationship with the genotype and the type of infection respectively. The great majority of isolates belonging to the same genotype were related to the same virulence factors, even though certain virulence factors were variable inside a genotype. However, the type of infection could not be related to any combination of virulence factors

Turning Emergency Plans into Executable Artifacts

ISBN: 978-0-692-21194-6 Available under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0) LicenseInternational audienceOn the way to the improvement of Emergency Plans, we show how a structured specification of the response procedures allows transforming static plans into dynamic, executable entities that can drive the way different actors participate in crisis responses. Additionally, the execution of plans requires the definition of information access mechanisms allowing execution engines to provide an actor with all the information resources he or she needs to accomplish a response task. We describe work in progress to improve the SAGA's Plan definition Module and Plan Execution Engine to support information-rich plan execution

Towards Digital Transformation of a City Resilience Framework

Improving city resilience is among the most challenging strategic goals for city administrators worldwide. To support their work, frameworks providing technical support and methodological guidance have been developed. Such frameworks define resilience improvement processes based on multidimensional resilience models to assess one city’s resilience level, plus a collection of policies to increase such level in different dimensions. Although some frameworks include software tools to support the process, their scope is limited to a particular step of the process, and global management is still done manually, hindering agility in the process. In this paper, we present our work towards the digital transformation of a city resilience framework. The use of process technology to specify and enact the process is combined with the application of model-based development techniques to provide interoperability of the different framework tools. We describe the architecture of the solution proposed, and the major features of our approach

Dual pathogenicity island transfer by piggybacking lateral transduction

Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during prophage induction. Here, we report that superantigen-carrying staphylococcal pathogenicity islands (SaPIs) employ a related but more versatile and complex mechanism of gene transfer to drive chromosomal hypermobility while self-transferring with additional virulence genes from the host. We found that after phage infection or prophage induction, activated SaPIs form concatamers in the bacterial chromosome by switching between parallel genomic tracks in replication bubbles. This dynamic life cycle enables SaPIbov1 to piggyback its LT of staphylococcal pathogenicity island vSaα, which encodes an array of genes involved in host-pathogen interactions, allowing both islands to be mobilized intact and transferred in a single infective particle. Our findings highlight previously unknown roles of pathogenicity islands in bacterial virulence and show that their evolutionary impact extends beyond the genes they carry