In Memoriam: Professor James W. Vaupel

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Effective elimination of Staphylococcal contamination from hospital surfaces by a bacteriophage-probiotic sanitation strategy: a monocentric study.

Persistent contamination of hospital surfaces and antimicrobial resistance (AMR) are recognized major causes of healthcare-associated infections (HAI). We recently showed that a probiotic-based sanitation (PCHS) can stably decrease surface pathogens and reduce AMR and HAIs. However, PCHS action is slow and non-specific. By contrast, bacteriophages have been proposed as a decontamination method as they can rapidly attack specific targets, but their routine application has never been tested. Here we analyzed the feasibility and effectiveness of phage addition to PCHS sanitation, aiming to obtain a rapid and stable abatement of specific pathogens in the hospital environment. Staphylococcal contamination in the bathrooms of General Medicine wards was analyzed, being such areas the most contaminated and Staphylococci the most prevalent bacteria in such settings. Results showed that a daily phage application by nebulization induced a rapid and significant decrease of Staphylococcus spp. load on treated surfaces, up to 97% more than PCHS alone (p<0.001), suggesting that such system might be considered as a part of prevention and control strategies, to counteract outbreaks of specific pathogens and prevent associated infections

Modeling of Immunosenescence and Risk of Death from Respiratory Infections: Evaluation of the Role of Antigenic Load and Population Heterogeneity

It is well known that efficacy of immune functions declines with age. It results in an increase of severity and duration of respiratory infections and also in dramatic growth of risk of death due to these diseases after age 65. The goal of this work is to describe and investigate the mechanism underlying the age pattern of the mortality rate caused by infectious diseases and to determine the cause-specific hazard rate as a function of immune system characteristics. For these purposes we develop a three-compartment model explaining observed risk-of-death. The model incorporates up-to-date knowledge about cellular mechanisms of aging, disease dynamics, population heterogeneity in resistance to infections, and intrinsic aging rate. The results of modeling show that the age-trajectory of mortality caused by respiratory infections may be explained by the value of antigenic load, frequency of infections and the rate of aging of the stem cell population (i.e. the population of T-lymphocyte progenitor cells). The deceleration of infection-induced mortality at advanced age can be explained by selection of individuals with a slower rate of stem cell aging. Parameter estimates derived from fitting mortality data indicate that infection burden was monotonically decreasing during the twentieth century, and changes in total antigenic load were gender-specific: it experienced periodic fluctuations in males and increased approximately two-fold in females

HHV-6A infection induces amyloid-beta expression and activation of microglial cells.

BACKGROUND: The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression. METHODS: We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay. RESULTS: We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form. CONCLUSIONS: In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection

First evidence of yawn contagion in a wild monkey species

Yawn contagion occurs when individuals yawn in response to the yawn of others (triggers). This is the first account of yawn contagion in wild geladas (Theropithecus gelada), a monkey species that shows yawn contagion in captivity and is organized in core units (one-male/bachelor groups) forming multilevel associations. In a population of geladas from the Kundi plateau (Ethiopia) we found that the yawning response was highest when geladas could perceive a triggering yawn, which confirms that yawn contagion is present in the wild. Yawn duration, mouth-opening degree and presence/absence of vocalisation (possibly modulating yawn detectability) did not affect the likelihood of contagion. Males and females, known to be both implicated in movement initiation within groups, were similarly powerful as yawn triggers. Instead, group membership and responder sex had a significant role in shaping the phenomenon. Yawn contagion was highest between individuals belonging to different core units and males were most likely to respond to others’ yawns. Because males have a non-negligible role in inter-group coordination, our results suggest that yawn contagion may have a communicative function that goes beyond the basic unit leve

Next-generation sequencing and PCR technologies in monitoring the hospital microbiome and its drug resistance

The hospital environment significantly contributes to the onset of healthcare-associated infections (HAIs), which represent one of the most frequent complications occurring in healthcare facilities worldwide. Moreover, the increased antimicrobial resistance (AMR) characterizing HAI-associated microbes is one of the human health’s main concerns, requiring the characterization of the contaminating microbial population in the hospital environment. The monitoring of surface microbiota in hospitals is generally addressed by microbial cultural isolation. However, this has some important limitations mainly relating to the inability to define the whole drug-resistance profile of the contaminating microbiota and to the long time period required to obtain the results. Hence, there is an urgent need to implement environmental surveillance systems using more effective methods. Molecular approaches, including next-generation sequencing and PCR assays, may be useful and effective tools to monitor microbial contamination, especially the growing AMR of HAI-associated pathogens. Herein, we summarize the results of our recent studies using culture-based and molecular analyses in 12 hospitals for adults and children over a 5-year period, highlighting the advantages and disadvantages of the techniques used

Pathogen Control in the Built Environment: A Probiotic-Based System as a Remedy for the Spread of Antibiotic Resistance

The high and sometimes inappropriate use of disinfectants and antibiotics has led to alarming levels of Antimicrobial Resistance (AMR) and to high water and hearth pollution, which today represent major threats for public health. Furthermore, the current SARS-CoV-2 pandemic has deeply influenced our sanitization habits, imposing the massive use of chemical disinfectants potentially exacerbating both concerns. Moreover, super-sanitation can profoundly influence the environmental microbiome, potentially resulting counterproductive when trying to stably eliminate pathogens. Instead, environmentally friendly procedures based on microbiome balance principles, similar to what applied to living organisms, may be more effective, and probiotic-based eco-friendly sanitation has been consistently reported to provide stable reduction of both pathogens and AMR in treated-environments, compared to chemical disinfectants. Here, we summarize the results of the studies performed in healthcare settings, suggesting that such an approach may be applied successfully also to non-healthcare environments, including the domestic ones, based on its effectiveness, safety, and negligible environmental impact

Next-generation sequencing and PCR technologies in monitoring the hospital microbiome and its drug resistance

The hospital environment significantly contributes to the onset of healthcare-associated infections (HAIs), which represent one of the most frequent complications occurring in healthcare facilities worldwide. Moreover, the increased antimicrobial resistance (AMR) characterizing HAI-associated microbes is one of the human health’s main concerns, requiring the characterization of the contaminating microbial population in the hospital environment. The monitoring of surface microbiota in hospitals is generally addressed by microbial cultural isolation. However, this has some important limitations mainly relating to the inability to define the whole drug-resistance profile of the contaminating microbiota and to the long time period required to obtain the results. Hence, there is an urgent need to implement environmental surveillance systems using more effective methods. Molecular approaches, including next-generation sequencing and PCR assays, may be useful and effective tools to monitor microbial contamination, especially the growing AMR of HAI-associated pathogens. Herein, we summarize the results of our recent studies using culture-based and molecular analyses in 12 hospitals for adults and children over a 5-year period, highlighting the advantages and disadvantages of the techniques used

Impact of a probiotic-based cleaning product on the microbiological profile of broiler litters and chicken caeca microbiota

ABSTRACT This study investigated for the first time the decontamination efficacy of a probiotic-based cleaning product containing Bacillus subtilis, Bacillus pumilus, and Bacillus megaterium spores on fresh and reused broiler litters during 3 rearing cycles of 6 wk each. Moreover, the impact of reused litters treated with the cleaning product on the chicken caeca microbiota was assessed at the end of the rearing cycles in comparison to untreated litter. The Bacillus spores provided with the cleaning treatment were able to successfully colonize the reused poultry litters, decreasing the mean counts of total aerobic bacteria, Enterobacteriaceae, and coagulase positive Staphylococci. The decrease of Enterobacteriaceae, mainly represented by the genus Escherichia, was also observed in the caeca of broilers reared on reused litters treated with the cleaning product. Moreover, the treatment retained the caeca content of Ruminococcaceae and Faecalibacterium as well as the level of biodiversity among the bacteria genera colonizing the caeca of animals reared on reused litter. Overall, the results of this study highlight a positive effect of the probiotic-based cleaning strategy on the microbial decontamination of reused litters and on broiler caeca stability, thereby enhancing animal health and prevention of poultry diseases