Antimicrobial Resistance in Aquaculture Environments: Unravelling the Complexity and Connectivity of the Underlying Societal Drivers.

Food production environments in low- and middle-income countries (LMICs) are recognized as posing significant and increasing risks to antimicrobial resistance (AMR), one of the greatest threats to global public health and food security systems. In order to maximize and expedite action in mitigating AMR, the World Bank and AMR Global Leaders Group have recommended that AMR is integrated into wider sustainable development strategies. Thus, there is an urgent need for tools to support decision makers in unravelling the complex social and environmental factors driving AMR in LMIC food-producing environments and in demonstrating meaningful connectivity with other sustainable development issues. Here, we applied the Driver-Pressure-State-Impact-Response (DPSIR) conceptual framework to an aquaculture case study site in rural Bangladesh, through the analysis of distinct social, microbiological, and metagenomic data sets. We show how the DPSIR framework supports the integration of these diverse data sets, first to systematically characterize the complex network of societal drivers of AMR in these environments and second to delineate the connectivity between AMR and wider sustainable development issues. Our study illustrates the complexity and challenges of addressing AMR in rural aquaculture environments and supports efforts to implement global policy aimed at mitigating AMR in aquaculture and other rural LMIC food-producing environments.

Hardwiring antimicrobial resistance mitigation into global policy.

In the wake of COVID-19, antimicrobial resistance (AMR) has become termed the 'silent pandemic', with a growing number of editorials warning that international momentum for AMR mitigation is being lost amidst the global turmoil of COVID-19, economic crises and the climate emergency. Yet, is it sufficient to now simply turn the volume of the pre-existing AMR policy discourse back up? Although existing AMR initiatives have previously achieved high levels of international attention, their impact remains limited. We believe it is time to critically reflect on the achievements of the past 7 years and adapt our AMR policies based on the substantial literature and evidence base that exists on the socioecological drivers of AMR. We argue that developing a more sustainable and impactful response requires a shift away from framing AMR as a unique threat in competition with other global challenges. Instead, we need to move towards an approach that emphasizes AMR as inherently interlinked and consciously hardwires upstream interventions into broader global developmental agendas.

Evaluating antimicrobial resistance in the global shrimp industry.

Antimicrobial resistance (AMR) is a growing threat to global public health, and the overuse of antibiotics in animals has been identified as a major risk factor. With high levels of international trade and direct connectivity to the aquatic environment, shrimp aquaculture may play a role in global AMR dissemination. The vast majority of shrimp production occurs in low- and middle-income countries, where antibiotic quality and usage is widely unregulated, and where the integration of aquaculture with family livelihoods offers many opportunities for human, animal and environmental bacteria to come into close contact. Furthermore, in shrimp growing areas, untreated waste is often directly eliminated into local water sources. These risks are very different to many other major internationally-traded aquaculture commodities, such as salmon, which is produced in higher income countries where there are greater levels of regulation and well-established management practices. Assessing the true scale of the risk of AMR dissemination in the shrimp industry is a considerable challenge, not least because obtaining reliable data on antibiotic usage is very difficult. Combating the risks associated with AMR dissemination is also challenging due to the increasing trend towards intensification and its associated disease burden, and because many farmers currently have no alternatives to antibiotics for preventing crop failure. In this review, we critically assess the potential risks the shrimp industry poses to AMR dissemination. We also discuss some of the possible risk mitigation strategies that could be considered by the shrimp industry as it strives for a more sustainable future in production.

Raising awareness of antimicrobial resistance in rural aquaculture practice in Bangladesh through digital communications: a pilot study.

One of the key strategic objectives of the World Health Organisation's global antimicrobial resistance (AMR) action plan is to improve public awareness and understanding of this issue. Very few AMR awareness campaigns have targeted the animal production sector, particularly in low- and middle-income countries (LMICs) where rural communities can be geographically difficult to access via traditional face-to-face community engagement methods. Aquaculture is a major food production industry in Bangladesh and across Asia, an area which poses a significant risk to global AMR dissemination. In this pilot study, we sought to investigate the potential for digital communication materials to rapidly and effectively communicate AMR messages to rural aquaculture farmers in Bangladesh. Working with stakeholders from the Bangladesh aquaculture industry, we developed a 4-minute digital animation designed specifically for this audience and assessed its capacity to engage and communicate AMR messages to farmers. We then conducted a small-scale social media campaign, to determine the potential for rapidly disseminating AMR awareness materials to a large audience across Bangladesh, where there is an extensive 4 G internet network and an ever-increasing proportion of the population (57% as of December 2019) have mobile internet access. Thirty-six farmers were surveyed: all of them liked this method of communication and 97% said it would change the way they use antibiotics in the future. Through the social media campaign, the animation received 9,100 views in the first 2 weeks alone. Although preliminary, these results demonstrate the huge potential for digital communication methods for the rapid and widespread communication of AMR awareness materials to rural aquaculture communities in Bangladesh and across Asia. Our results support the need for more research into the most appropriate and effective content of AMR awareness campaigns for aquaculture communities and question the need for explaining the science underlying AMR in such communication materials.

Differential roles of the PKC novel isoforms, PKCdelta and PKCepsilon, in mouse and human platelets.

BACKGROUND: Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we focus on the role of two novel PKC isoforms, PKCdelta and PKCepsilon, in both mouse and human platelets. PKCdelta is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCdelta undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCepsilon, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCepsilon in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRgamma-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. CONCLUSIONS: These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms delta and epsilon in human and mouse platelets and a selective role for PKCepsilon in signalling through GPVI.

Distinct but critical roles for integrin alphaIIbbeta3 in platelet lamellipodia formation on fibrinogen, collagen-related peptide and thrombin.

Integrins are the major receptor type known to facilitate cell adhesion and lamellipodia formation on extracellular matrix proteins. However, collagen-related peptide and thrombin have recently been shown to mediate platelet lamellipodia formation when presented as immobilized surfaces. The aims of this study were to establish if there exists a role for the platelet integrin alpha(IIb)beta(3) in this response; and if so, whether signalling from the integrin is required for lamellipodia formation on these surfaces. Real-time analysis was used to compare platelet morphological changes on surfaces of fibrinogen, collagen-related peptide or thrombin in the presence of various pharmacological inhibitors and platelets from 'knockout' mice. We demonstrate that collagen-related peptide and thrombin stimulate distinct patterns of platelet lamellipodia formation and elevation of intracellular Ca(2+) to that induced by the integrin alpha(IIb)beta(3) ligand, fibrinogen. Nevertheless, lamellipodia formation on collagen-related peptide and thrombin is dependent upon engagement of alpha(IIb)beta(3), consistent with release of alpha(IIb)beta(3) ligand(s) from platelet granules. However, the requirement for signalling by the integrin on fibrinogen can be bypassed by the addition of thrombin to the solution. These observations reveal a critical role for alpha(IIb)beta(3) in forming lamellipodia on collagen-related peptide and thrombin which is dependent on its ability to function as an adhesive receptor but not necessarily on its ability to signal. These results suggest that integrins may play an important role in lamellipodia formation triggered by nonintegrin ligands in platelets and possibly in other cell types.