Maura Manganelli

Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation

Abstract Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

Impact of climate change on waterborne diseases

Change in climate and water cycle will challenge water availability but it will also increase the exposure to unsafe water. Floods, droughts, heavy storms, changes in rain pattern, increase of temperature and sea level, they all show an increasing trend worldwide and will affect biological, physical and chemical components of water through different paths thus enhancing the risk of waterborne diseases. This paper is intended, through reviewing the available literature, to highlight environmental changes and critical situations caused by floods, drought and warmer temperature that will lead to an increase of exposure to water related pathogens, chemical hazards and cyanotoxins. The final aim is provide knowledge-based elements for more focused adaptation measures.

Health risk evaluation associated to Planktothrix rubescens: An integrated approach to design tailored monitoring programs for human exposure to cyanotoxins

Increasing concern for human health related to cyanotoxin exposure imposes the identification of pattern and level of exposure; however, current monitoring programs, based on cyanobacteria cell counts, could be inadequate. An integrated approach has been applied to a small lake in Italy, affected by Planktothrix rubescens blooms, to provide a scientific basis for appropriate monitoring program design. The cyanobacterium dynamic, the lake physicochemical and trophic status, expressed as nutrients concentration and recycling rates due to bacterial activity, the identification/quantification of toxic genotype and cyanotoxin concentration have been studied. Our results indicate that low levels of nutrients are not a marker for low risk of P. rubescens proliferation and confirm that cyanobacterial density solely is not a reliable parameter to assess human exposure. The ratio between toxic/non-toxic cells, and toxin concentrations, which can be better explained by toxic population dynamic, are much more diagnostic, although varying with time and environmental conditions. The toxic fraction within P. rubescens population is generally high (30-100%) and increases with water depth. The ratio toxic/non-toxic cells is lowest during the bloom, suggesting a competitive advantage for non-toxic cells. Therefore, when P. rubescens is the dominant species, it is important to analyze samples below the thermocline, and quantitatively estimate toxic genotype abundance. In addition, the identification of cyanotoxin content and congeners profile, with different toxic potential, are crucial for risk assessment.

Emerging health issues of cyanobacterial blooms

This paper describes emerging issue related to cyanobacterial dynamics and toxicity and human health risks. Data show an increasing cyanobacteria expansion and dominance in many environments. However there are still few information on the toxic species fitness, or on the effects of specific drivers on toxin production. Open research fields are related to new exposure scenario (cyanotoxins in water used for haemodialysis and in food supplements); to new patterns of co-exposure between cyanotoxins and algal toxins and/or anthropogenic chemicals; to dynamics affecting toxicity and production of different cyanotoxin variants under environmental stress; to the accumulation of cyanotoxins in the food web. In addition, many data gaps exist in the characterization of the toxicological profiles, especially about long term effects.

Microbial mechanisms coupling carbon and phosphorus cycles in phosphorus-limited northern Adriatic Sea

The coastal northern Adriatic Sea receives pulsed inputs of riverine nutrients, causing phytoplankton blooms and seasonally sustained dissolved organic carbon (DOC) accumulation-hypothesized to cause episodes of massive mucilage. The underlying mechanisms regulating P and C cycles and their coupling are unclear. Extensive biogeochemical parameters, processes and community composition were measured in a 64-day mesocosms deployed off Piran, Slovenia. We followed the temporal trends of C and P fluxes in P-enriched (P+) and unenriched (P-) mesocosms. An intense diatom bloom developed then crashed; however, substantial primary production was maintained throughout, supported by tightly coupled P regeneration by bacteria and phytoplankton. Results provide novel insights on post-bloom C and P dynamics and mechanisms. 1) Post-bloom DOC accumulation to 186 μM remained elevated despite high bacterial carbon demand. Presumably, a large part of DOC accumulated due to the bacterial ectohydrolytic processing of primary productivity that adventitiously generated slow-to-degrade DOC; 2) bacteria heavily colonized post-bloom diatom aggregates, rendering them microscale hotspots of P regeneration due to locally intense bacterial ectohydrolase activities; 3) Pi turnover was rapid thus suggesting high P flux through the DOP pool (dissolved organic phosphorus) turnover; 4) Alpha- and Gamma-proteobacteria dominated the bacterial communities despite great differences of C and P pools and fluxes in both mesocosms. However, minor taxa showed dramatic changes in community compositions. Major OTUs were presumably generalists adapted to diverse productivity regimes.We suggest that variation in bacterial ectohydrolase activities on aggregates, regulating the rates of POM→DOM transition as well as dissolved polymer hydrolysis, could become a bottleneck in P regeneration. This could be another regulatory step, in addition to APase, in the microbial regulation of P cycle and the coupling between C and P cycles.

Cyanobacteria blooms in water: Italian guidelines to assess and manage the risk associated to bathing and recreational activities

Cyanobacteria thrive in many aquatic environments, where they can produce cyanotoxins with different toxicological profile. Anthropic pressure and climate changes are causing the expansion in terms of time and space of their blooms, increasing the concerns for human health in several exposure scenarios. Here the update of the Italian guidelines for the management of cyanobacterial blooms in bathing water is presented. A risk-based approach has been developed according to the current scientific knowledge on cyanobacteria distribution in the Italian Lakes and on chemical, toxicological and epidemiological aspects of different cyanotoxins, summarized in the first part of the paper. Oral, dermal and inhalation exposure to cyanotoxins, during recreational activities, are individually examined, to develop a framework of thresholds and actions aimed at preventing harmful effects for bathers. Guidelines, also by comparing international guidance values and/or guidelines, provide criteria to plan environmental monitoring activities, health surveillance and public communication systems. Finally the still important scientific gaps and research needs are highlighted.

Cyanobacteria biomagnification and amyotrophic lateral sclerosis.

We found that malignant cells and tumors contain very little low molecular weight (MW) peptides and amino acids compared to normal cells and tissues. However, the low molecular weight (MW) peptides that inhibit mitosis, cell growth and cause differentiation were recovered from cell growth medium or ascites. We therefore hypothesize that out transport and, or diffusion of the low MW compounds is possibly central to carcinogenesis, since the controlling low MW signals are lost from the cell. Without inhibitors mitosis should not or would not stop. Hypothesis: Loss of low MW peptides and amino acids may be a common trait in carcinogenesis. It would entail that normal cell regulation such as growth, mitosis inhibition and differentiation would probably be lost, especially as we recover the missing compounds (chalones) from the incubation fluid or ascites. The chalones and deprimerones seem to induce differentiation of cells when inhibiting mitosis, and when lost from the cells may explain the de-differentiation typical of malignant cells. Such a mechanism would make room for membrane damaging mechanical, inflammatory and chemical as well as viral aetiologies in carcinogenesis. Faster than normal growth also increases the probability of geneic malfunction. 2013 Published by Elsevier Ltd.