Tuberculosis is a current major world-health problem, exacerbated by the causative pathogen, Mycobacterium tuberculosis (Mtb), becoming increasingly resistant to conventional antibiotic treatment. Mtb is able to counteract the bactericidal mechanisms of leukocytes to survive intracellularly and develop a niche permissive for proliferation and dissemination. Understanding of the pathogenesis of mycobacterial infections such as tuberculosis (TB) remains limited, especially for early infection and for reactivation of latent infection. Signaling via hypoxia inducible factor α (HIF-α) transcription factors has previously been implicated in leukocyte activation and host defence. We have previously shown that hypoxic signaling via stabilization of Hif-1α prolongs the functionality of leukocytes in the innate immune response to injury. We sought to manipulate Hif-α signaling in a well-established Mycobacterium marinum (Mm) zebrafish model of TB to investigate effects on the host's ability to combat mycobacterial infection. Stabilization of host Hif-1α, both pharmacologically and genetically, at early stages of Mm infection was able to reduce the bacterial burden of infected larvae. Increasing Hif-1α signaling enhanced levels of reactive nitrogen species (RNS) in neutrophils prior to infection and was able to reduce larval mycobacterial burden. Conversely, decreasing Hif-2α signaling enhanced RNS levels and reduced bacterial burden, demonstrating that Hif-1α and Hif-2α have opposing effects on host susceptibility to mycobacterial infection. The antimicrobial effect of Hif-1α stabilization, and Hif-2α reduction, were demonstrated to be dependent on inducible nitric oxide synthase (iNOS) signaling at early stages of infection. Our findings indicate that induction of leukocyte iNOS by stabilizing Hif-1α, or reducing Hif-2α, aids the host during early stages of Mm infection. Stabilization of Hif-1α therefore represents a potential target for therapeutic intervention against tuberculosis.

Introduction: Laboratory biosecurity is of continuously growing interest due to increasing concerns about deliberate misuse of biological materials and emerging biological risks. These risks continue to be magnified by globalization, the rapid pace of scientific development, and dual-use technologies. Worldwide laboratory capacities are expanding, which calls for concrete actions to improve laboratory biosafety and biosecurity practices to protect researchers and the community. Hence, laboratories require comprehensive biorisk management programs to minimize the risk of accidental and deliberate release of infectious biological materials. Objective: Malaysia has prioritized the concern of national biosecurity and aims to consolidate laboratory biosecurity performance to detect and prevent the deliberate release of biological agents. Methods: Two 3-day workshops were organized over the course of four months in which Malaysia collaborated with The Netherlands. This bilateral engagement aimed to integrate biosecurity practices in their national biorisk management programs, and resulted into a comprehensive biosecurity checklist for laboratory assessment and monitoring. Results: This biosecurity checklist is based on Malaysian and Dutch expert opinions and national and international guidelines and regulations. The biosecurity checklist is a survey-driven tool that consists of a set of concrete questions for each key biosecurity area, which are discussion points for assessment. Conclusion: We display a practical biosecurity checklist for laboratory assessment and monitoring. Although the presented checklist was the template for the specific Malaysia checklist, it could serve as a template for other countries.

One of the challenges of global biosecurity is to protect and control dangerous pathogens from unauthorized access and intentional release. A practical and feasible option to protect life science institutes against theft and sabotage, and secure their biological materials against misuse, is to establish a national electronic database with a comprehensive overview of the locations of all controlled dangerous pathogens in a country. This national database could be used as an instrument to secure and account for dangerous pathogens in a country, but it could also assist in establishing a biosecurity assessing and monitoring system for laboratories that work with these controlled biological agents. The Republic of Uganda is one of the first countries, prompted by the World Health Organization's (WHO's) Joint External Evaluation (JEE), to implement a national electronic database that assembles information collected from relevant Ugandan laboratories. This Ugandan Inventory of Dangerous Pathogens is different from an institute-specific pathogen inventory system, as it is intended to store the information collected from laboratories in the country working with dangerous pathogens in 1 centralized secure location. The Uganda National Council for Science and Technology (UNCST) has coordinated the implementation of the Ugandan national inventory. The inventory was recognized by the WHO JEE as contributing to Uganda's developed capacities regarding biosafety and biosecurity. This article describes the steps in implementing Uganda's National Inventory of Dangerous Pathogens. In addition, it presents a straightforward approach that can be adapted by other countries that aim to enhance their biosecurity capacities.