Staphylococcus aureus in animals

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 community-acquired infections. Despite the prevalence of literature characterising staphylococcal pathogenesis in humans, S. aureus is a major cause of infection and disease in a plethora of animal hosts leading to a significant impact on public health and agriculture. Infections in animals are deleterious to animal health, and animals can act as a reservoir for staphylococcal transmission to humans. Host-switching events between humans and animals and amongst animals are frequent and have been accentuated with the domestication and/or commercialisation of specific animal species. Host-switching is typically followed by subsequent adaptation through acquisition and/or loss of mobile genetic elements such as phages, pathogenicity islands and plasmids as well as further host-specific mutations allowing it to expand into new host populations. In this chapter, we will be giving an overview of S. aureus in animals, how this bacterial species was, and is, being transferred to new host species and the key elements thought to be involved in its adaptation to new ecological host niches. We will also highlight animal hosts as a reservoir for the development and transfer of antimicrobial resistance determinants

Virus satellites drive viral evolution and ecology

Virus satellites are widespread subcellular entities, present both in eukaryotic and in prokaryotic cells. Their modus vivendi involves parasitism of the life cycle of their inducing helper viruses, which assures their transmission to a new host. However, the evolutionary and ecological implications of satellites on helper viruses remain unclear. Here, using staphylococcal pathogenicity islands (SaPIs) as a model of virus satellites, we experimentally show that helper viruses rapidly evolve resistance to their virus satellites, preventing SaPI proliferation, and SaPIs in turn can readily evolve to overcome phage resistance. Genomic analyses of both these experimentally evolved strains as well as naturally occurring bacteriophages suggest that the SaPIs drive the coexistence of multiple alleles of the phage-coded SaPI inducing genes, as well as sometimes selecting for the absence of the SaPI depressing genes. We report similar (accidental) evolution of resistance to SaPIs in laboratory phages used for Staphylococcus aureus typing and also obtain the same qualitative results in both experimental evolution and phylogenetic studies of Enterococcus faecalis phages and their satellites viruses. In summary, our results suggest that helper and satellite viruses undergo rapid coevolution, which is likely to play a key role in the evolution and ecology of the viruses as well as their prokaryotic hosts

A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species

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 populations are influenced by powerful forces such as genetic drift that reduce the fixation rate of beneficial mutations, limiting the capacity for host adaptation. Here, we implement a novel experimental model of bacterial host switching to investigate the ability of the multihost pathogen Staphylococcus aureus to adapt to new species under continuous population bottlenecks. We demonstrate that beneficial mutations accumulated during infection can overcome genetic drift and sweep through the population, leading to host adaptation. Our findings highlight the remarkable capacity of some bacteria to adapt to distinct host niches in the face of powerful antagonistic population forces.status: publishe

Phage-inducible chromosomal islands as a diagnostic platform to capture and detect bacterial pathogens

Phage-inducible chromosomal islands (PICIs) are a family of phage satellites that hijack phage components to facilitate their mobility and spread. Recently, these genetic constructs are repurposed as antibacterial drones, enabling a new toolbox for unorthodox applications in biotechnology. To illustrate a new suite of functions, the authors have developed a user-friendly diagnostic system, based upon PICI transduction to selectively enrich bacteria, allowing the detection and sequential recovery of Escherichia coli and Staphylococcus aureus. The system enables high transfer rates and sensitivities in comparison with phages, with detection down to ≈50 CFU mL−1. In contrast to conventional detection strategies, which often rely on nucleic acid molecular assays, and cannot differentiate between dead and live organisms, this approach enables visual sensing of viable pathogens only, through the expression of a reporter gene encoded in the PICI. The approach extends diagnostic sensing mechanisms beyond cell-free synthetic biology strategies, enabling new synthetic biology/biosensing toolkits

Phage-inducible chromosomal islands as a diagnostic platform to capture and detect bacterial pathogens

Phage-inducible chromosomal islands (PICIs) are a family of phage satellites that hijack phage components to facilitate their mobility and spread. Recently, these genetic constructs are repurposed as antibacterial drones, enabling a new toolbox for unorthodox applications in biotechnology. To illustrate a new suite of functions, the authors have developed a user-friendly diagnostic system, based upon PICI transduction to selectively enrich bacteria, allowing the detection and sequential recovery of Escherichia coli and Staphylococcus aureus. The system enables high transfer rates and sensitivities in comparison with phages, with detection down to ≈50 CFU mL−1. In contrast to conventional detection strategies, which often rely on nucleic acid molecular assays, and cannot differentiate between dead and live organisms, this approach enables visual sensing of viable pathogens only, through the expression of a reporter gene encoded in the PICI. The approach extends diagnostic sensing mechanisms beyond cell-free synthetic biology strategies, enabling new synthetic biology/biosensing toolkits

Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2-5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept

Background: Patients with polyarticular-course juvenile idiopathic arthritis (pJIA), receiving disease-modifying anti-rheumatic drugs with immunosuppressive effects, may be at increased risk of vaccine-preventable infections. This substudy assessed protective antibody responses to diphtheria and tetanus vaccination given prior to study enrolment in patients with pJIA. Findings: This was a substudy of a 24-month, single-arm, open-label, multicenter, Phase III trial (NCT01844518) of subcutaneous abatacept in children with active pJIA (N = 219). Patients aged 2-5 years, with 652 continuous months of weekly weight-tiered (10-< 25 kg [50 mg], 25-< 50 kg [87.5 mg]) subcutaneous abatacept treatment (with/without methotrexate and/or low-dose corticosteroids), who received diphtheria/tetanus vaccine prior to enrolment, were eligible. Protective antibody levels to diphtheria/tetanus (> 0.1 IU/mL), and safety, were assessed. Overall, 29 patients were analyzed: 19 (65.5%), 1 (3.4%) and 9 (31.0%) patients had > 12, 6-12 and 2-< 6 months of abatacept exposure, respectively. All patients had protective antibody levels to tetanus and 26 (89.7%) patients had protective antibody levels to diphtheria. Of the 3 patients without protective antibody levels to diphtheria, each had an antibody level of 0.1 IU/mL, bordering the lower threshold of protection. Concomitant use of methotrexate and/or low-dose corticosteroids had no evident effect on antibody levels. No unexpected adverse events, including cases of diphtheria or tetanus, were reported during the 24-month period. Conclusions: Patients aged 2-5 years with pJIA who received 2-24 months of weekly subcutaneous abatacept, with or without concomitant methotrexate and/or low-dose corticosteroids, maintained effective diphtheria and tetanus vaccination protection without new safety signals

Suspended silicon mid-infrared waveguide devices with subwavelength grating metamaterial cladding

We present several fundamental photonic building blocks based on suspended silicon waveguides supported by a lateral cladding comprising subwavelength grating metamaterial. We discuss the design, fabrication, and characterization of waveguide bends, multimode interference devices and Mach-Zehnder interferometers for the 3715 - 3800 nm wavelength range, demonstrated for the first time in this platform. The waveguide propagation loss of 0.82 dB/cm is reported, some of the lowest loss yet achieved in silicon waveguides for this wavelength range. These results establish a direct path to ultimately extending the operational wavelength range of silicon wire waveguides to the entire transparency window of silicon

Biofilms bacterianos e infección

En los países desarrollados tendemos a pensar que las principales causas de mortalidad son las enfermedades cardiovasculares y el cáncer en sus múltiples modalidades. Sin embargo, los datos en Europa resultan elocuentes; las enfermedades infecciosas representan la segunda causa de mortalidad (14,9 millones de muertes), después de las enfermedades cardiovasculares (16,9 millones de muertes) y causan el doble de muertes que el cáncer (7,1 millones de muertes) (datos del World Health Organization, WHO, 2002). Los agentes infecciosos responsables de mortalidad en el hombre han ido evolucionando a medida que las medidas higiénicas y las técnicas médicas han ido evolucionando. Actualmente, las enfermedades infecciosas agudas causadas por bacterias patógenas especializadas como la difteria, tétanos, peste, cólera o la tosferina, que representaban la principal causa de muerte a principios del siglo XX, han sido controladas gracias a la acción de los antibióticos y de las vacunas. En su lugar, más de la mitad de las infecciones que afectan a pacientes ligeramente inmunocomprometidos son producidas por bacterias ubicuas, capaces de producir infecciones de tipo crónico, que responden pobremente a los tratamientos antibióticos y no pueden prevenirse mediante inmunización. Ejemplos de estas infecciones son la otitis media, endocarditis de válvulas nativas, infecciones urinarias crónicas, infecciones de próstata, osteomielitis y todas las infecciones relacionadas con implantes. El análisis directo de los implantes y tejidos de estas infecciones muestra claramente que en la mayoría de los casos la bacteria responsable de la infección crece adherida sobre el tejido o el implante formando comunidades de bacterias a las que se les ha denominado “biofilms”. Dentro del biofilm, las bacterias están protegidas de la acción de los anticuerpos, del ataque de las células fagocíticas y de los tratamientos antimicrobianos. En este artículo se describe el papel que juegan los biofilms en infecciones humanas persistentes

Silicon-based photonic integrated circuits for the mid-infrared

AbstractSilicon-based photonic integrated circuits (PICs) operating in the mid-infrared wavelength range are presented. Firstly, it is shown that the operation of the SOI-based waveguide circuits can be pushed beyond the telecom window till a wavelength of 4μm. Ge-on-Si based PICs are demonstrated for operation beyond 4μm wavelength. Low-loss waveguides and integrated spectrometers are reported for both the waveguide platforms. We also present our results on efficient thermo-optic phase shifters for germanium waveguide circuits

Hijacking the hijackers: Escherichia coli pathogenicity islands redirect helper phage packaging for their own benefit

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 genetic and structural analyses, we solve the mystery here by showing that the Gram-negative PICIs encode a protein that simultaneously performs these processes. This protein, which we have named Rpp (for redirecting phage packaging), interacts with the phage terminase small subunit, forming a heterocomplex. This complex is unable to recognize the phage DNA, blocking phage packaging, but specifically binds to the PICI genome, promoting PICI packaging. Our studies reveal the mechanism of action that allows PICI dissemination in nature, introducing a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial pathogen evolution