Emergence of new variants of antibiotic resistance genomic islands among multidrug-resistant Salmonella enterica in poultry.

Non-typhoidal Salmonella enterica (NTS) are diverse and important bacterial pathogens consisting of more than 2600 different serovars, with varying host-specificity. Here, we characterized the poultry-associated serovars in Israel, analysed their resistome and illuminated the molecular mechanisms underlying common multidrug resistance (MDR) patterns. We show that at least four serovars including Infantis, Muenchen, Newport and Virchow present a strong epidemiological association between their temporal trends in poultry and humans. Worrisomely, 60% from all of the poultry isolates tested (n = 188) were multidrug resistant, mediated by chromosomal SNPs and different mobile genetics elements. A novel streptomycin-azithromycin resistance island and previously uncharacterized versions of the mobilized Salmonella genomic island 1 (SGI1) were identified and characterized in S. Blockley and S. Kentucky isolates respectively. Moreover, we demonstrate that the acquisition of SGI1 does not impose fitness cost during growth under nutrient-limited conditions or in the context of Salmonella infection in the mouse model. Overall, our data emphasize the role of the poultry production as a pool of specific epidemic MDR strains and autonomous genetic elements, which confer resistance to heavy metals and medically relevant antibiotics. These are likely to disseminate to humans via the food chain and fuel the increasing global antibiotic resistance crisis.

Differences in the expression of SPI-1 genes pathogenicity and epidemiology between the emerging Salmonella enterica serovar Infantis and the model Salmonella enterica serovar Typhimurium.

BACKGROUND: Salmonella enterica serovar Infantis (S. Infantis) is one of the ubiquitous serovars of the bacterial pathogen S. enterica and recently has been emerging in many countries worldwide. Nonetheless, not much is known about its epidemiology, host adaptation, and virulence. METHODS: Epidemiological and molecular approaches were used together with tissue-culture and mouse models to conduct phenotypic comparison with the model S. enterica serovar Typhimurium. RESULTS: We show that S. Infantis is more frequently associated with infections in infants <2 years old and prone to cause significantly less invasive infections than serovar Typhimurium. Moreover, although S. Infantis adheres better to host cells and highly colonizes mouse intestines soon after infection, it is significantly less invasive and induces much lower inflammation and disease in vivo than S. Typhimurium. These differences were associated with lower expression of Salmonella pathogenicity island (SPI) 1 genes in S. Infantis than in S. Typhimurium. CONCLUSIONS: Our results demonstrate previously unknown differences in the epidemiology, virulence pathway expression, and pathogenicity between two highly abundant Salmonella serovars and suggest that native variation in the expression of the SPI-1 regulon is likely to contribute to epidemiological and virulence variation between genetically similar nontyphoidal Salmonella serovars.

The emergence of a multidrug resistant Salmonella Muenchen in Israel is associated with horizontal acquisition of the epidemic pESI plasmid.

OBJECTIVES: Horizontal acquisition of mobile genetic elements is a powerful evolutionary driving force that can profoundly affect pathogens epidemiology and their interactions with the environment and host. In the last decade, the role of the epidemic megaplasmid, pESI was demonstrated in the global emergence of multi-drug resistant (MDR) Salmonella enterica serovar Infantis strains, but it was unknown if this was a one-time phenomenon, or that pESI can drive the emergence of other pathogens. METHODS: Epidemiological, molecular, whole genome sequencing, de-novo assembly, bioinformatics and genetic approaches were used to analyze the emergence of a pESI-positive Salmonella enterica serovar Muenchen strain in Israel. RESULTS: Since 2018, we report the emergence and high prevalence of S. Muenchen in Israel, which consisted at 2020, 40% (1055/2671) of all clinical Salmonella isolates. We show that the emergence of S. Muenchen is dominated by a clonal MDR strain, report its complete assembled genome sequence, and demonstrate that in contrast to preemergent strains, it harbors the epidemic megaplasmid, pESI, which can be self-mobilized into E. coli and other Salmonella serovars. Additionally, we identified bioinformatically highly similar genomes of clinical isolates that were recently collected in South Africa, UK and USA. CONCLUSIONS: This is a second documented case of a pathogen emergence associated with pESI acquisition. Considering the genetic cargo of pESI that enhances resistance, stress tolerance and virulence, and its ability to conjugate into prevalent Salmonella serovars, we provide further support that pESI facilities the emergence and spreading of new Salmonella strains.

Nuclear lamins: key regulators of nuclear structure and activities.

The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM), where it associates with the peripheral chromatin. It contains lamins and lamin-associated proteins, including many integral proteins of the INM, chromatin modifying proteins, transcriptional repressors and structural proteins. A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins. The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm. Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'. This review concentrates mainly on lamins, their structure and their roles in DNA replication, chromatin organization, adult stem cell differentiation, aging, tumorogenesis and the lamin mutations leading to laminopathic diseases.

Structure of algal-born phenolic polymeric adhesives.

Adhesive materials extracted from the brown alga Fucus serratus are composed of phenolic polymer, alginate, and CaCl2. The phenolic polymer undergoes an oxidation reaction in the presence of bromoperoxidase, KI, and H2O2. The nanostructure of the adhesive was investigated using small angle X-ray scattering, light scattering, and cryo- transmission electron microscopy experiments. These have shown that the phenolic polymer undergoes self-assembly and forms flexible chain-like objects. Oxidation or adding alginate does not alter this structure. However, once calcium ions are added, a rigid network is formed. Presumably, this network is responsible for the cohesive strength of the glue.

BAF-1 mobility is regulated by environmental stresses.

Barrier to autointegration factor (BAF) is an essential component of the nuclear lamina that binds lamins, LEM-domain proteins, histones, and DNA. Under normal conditions, BAF protein is highly mobile when assayed by fluorescence recovery after photobleaching and fluorescence loss in photobleaching. We report that Caenorhabditis elegans BAF-1 mobility is regulated by caloric restriction, food deprivation, and heat shock. This was not a general response of chromatin-associated proteins, as food deprivation did not affect the mobility of heterochromatin protein HPL-1 or HPL-2. Heat shock also increased the level of BAF-1 Ser-4 phosphorylation. By using missense mutations that affect BAF-1 binding to different partners we find that, overall, the ability of BAF-1 mutants to be immobilized by heat shock in intestinal cells correlated with normal or increased affinity for emerin in vitro. These results show BAF-1 localization and mobility at the nuclear lamina are regulated by stress and unexpectedly reveal BAF-1 immobilization as a specific response to caloric restriction in C. elegans intestinal cells.

Persistence of cyprinid herpesvirus 3 in infected cultured carp cells.

Cyprinid herpesvirus 3 (CyHV-3), previously designated carp interstitial nephritis and gill necrosis virus or koi herpesvirus, is the cause of a worldwide mortal disease of koi and carp. Morphologically, the virus resembles herpesviruses, yet it bears a genome of 277 to 295 kbp, which is divergent from most of the genomic sequences available in GenBank. The disease afflicts fish in the transient seasons, when the water temperature is 18 to 28 degrees C, conditions which permit virus propagation in cultured cells. Here we report that infectious virus is preserved in cultured cells maintained for 30 days at 30 degrees C. CyHV-3-infected vacuolated cells with deformed morphology converted to normal, and plaques disappeared following shifting up of the temperature and reappeared after transfer to the permissive temperature. Viral propagation and viral gene transcription were turned off by shifting cells to the nonpermissive temperature. Upon return of the cells to the permissive temperature, transcription of viral genes was reactivated in a sequence distinguished from that occurring in naïve cells following infection. Our results show that CyHV-3 persists in cultured cells maintained at the nonpermissive temperature and suggest that viruses could persist for long periods in the fish body, enabling a new burst of infection upon a shift to a permissive temperature.

Detection of carp interstitial nephritis and gill necrosis virus in fish droppings.

Carp interstitial nephritis and gill necrosis virus (CNGV) is an unclassified large DNA virus that morphologically resembles members of the Herpesviridae but contains a large (ca. approximately 280-kbp) linear double-stranded DNA. This virus has also been named koi herpesvirus, koi herpes-like virus, and cyprinid herpesvirus 3. CNGV is the cause of a lethal disease that afflicts common carp and koi. By using immunohistochemistry, molecular analysis, and electron microscopy we previously demonstrated that this virus is present mainly in the intestine and kidney of infected fish. Based on these observations, we postulated that viruses and/or viral components may appear in droppings of infected carp. Here we report that (i) by using PCR we demonstrated that fish droppings contain viral DNA, (ii) fish droppings contain viral antigens which are useful for CNGV diagnosis, and (iii) fish droppings contain active virus which can infect cultured common carp brain cells and induce the disease in naïve fish following inoculation. Thus, our findings show that CNGV can be identified by using droppings without taking biopsies or killing fish and that infectious CNGV is present in the stools of sick fish. The possibility that fish droppings preserve viable CNGV during the nonpermissive seasons is discussed.