Despite highly specialized international interventions and policies in place today, the rapid emergence and dissemination of resistant bacterial species continue to occur globally, threatening the longevity of antibiotics in the medical sector. In particular, problematic nosocomial infections caused by multidrug resistant Gram-negative pathogens present as a major burden to both patients and healthcare systems, with annual mortality rates incrementally rising. Bacteriocins, peptidic toxins produced by bacteria, offer promising potential as substitutes or conjugates to current therapeutic compounds. These non-toxic peptides exhibit significant potency against certain bacteria (including multidrug-resistant species), while producer strains remain insusceptible to the bactericidal peptides. The selectivity and safety profile of bacteriocins have been highlighted as superior advantages over traditional antibiotics; however, many aspects regarding their efficacy are still unknown. Although active at low concentrations, bacteriocins typically have low in vivo stability, being susceptible to degradation by proteolytic enzymes. Another major drawback lies in the feasibility of large-scale production, with these key features collectively limiting their current clinical application. Though such limitations require extensive research, the concept of expanding bacteriocins from food preservation to human health opens many fascinating doors, including novel drug delivery systems and anticancer treatment applications.

Antimicrobial resistance is one of the greatest dangers to public health of the 21st century, threatening the treatment and prevention of infectious diseases globally. Disinfection, the elimination of microbial species via the application of biocidal chemicals, is essential to control infectious diseases and safeguard animal and human health. In an era of antimicrobial resistance and emerging disease, the effective application of biocidal control measures is vital to protect public health. The COVID-19 pandemic is an example of the increasing demand for effective biocidal solutions to reduce and eliminate disease transmission. However, there is increasing recognition into the relationship between biocide use and the proliferation of Antimicrobial Resistance species, particularly multidrug-resistant pathogens. The One Health approach and WHO action plan to combat AMR require active surveillance and monitoring of AMR species; however, biocidal resistance is often overlooked. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens and numerous fungal species have demonstrated drug and biocidal resistance where increased patient mortality is a risk. Currently, there is a lack of information on the impact of biocide application on environmental habitats and ecosystems. Undoubtedly, the excessive application of disinfectants and AMR will merge to result in secondary disasters relating to soil infertility, loss of biodiversity and destruction of ecosystems.

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems.

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Mushrooms have been used as traditional medicine for millennia, fungi are the main natural source of psychedelic compounds. There is now increasing interest in using fungal active compounds such as psychedelics for alleviating symptoms of mental health disorders including major depressive disorder, anxiety, and addiction. The anxiolytic, antidepressant and anti-addictive effect of these compounds has raised awareness stimulating neuropharmacological investigations. Micro-dosing or acute dosing with psychedelics including Lysergic acid diethylamide (LSD )and psilocybin may offer patients treatment options which are unmet by current therapeutic options. Studies suggest that either dosing regimen produces a rapid and long-lasting effect on the patient post administration with a good safety profile. Psychedelics can also modulate immune systems including pro-inflammatory cytokines suggesting a potential in the treatment of auto-immune and other chronic pain conditions. This literature review aims to explore recent evidence relating to the application of fungal bioactives in treating chronic mental health and chronic pain morbidities.

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Antimicrobial resistance (AMR) remains one of the greatest public health-perturbing crises of the 21st century, where species have evolved a myriad of defence strategies to resist conventional therapy. The production of extended-spectrum β-lactamase (ESBL), AmpC and carbapenemases in Gram-negative bacteria (GNB) is one such mechanism that currently poses a significant threat to the continuity of first-line and last-line β-lactam agents, where multi-drug-resistant GNB currently warrant a pandemic on their own merit. The World Health Organisation (WHO) has long recognised the need for an improved and coordinated global effort to contain these pathogens, where two factors in particular, international travel and exposure to antimicrobials, play an important role in the emergence and dissemination of antibiotic-resistant genes. Studies described herein assess the resistance patterns of isolated nosocomial pathogens, where levels of resistance were detected using recognised in vitro methods. Additionally, studies conducted extensively investigated alternative biocide (namely peracetic acid, triameen and benzalkonium chloride) and therapeutic options (specifically 1,10-phenanthroline-5,6-dione), where the levels of induced endotoxin from E. coli were also studied for the latter. Antibiotic susceptibility testing revealed there was a significant association between multi-drug resistance and ESBL production, where the WHO critical-priority pathogens, namely E. coli, K. pneumoniae, A. baumannii and P. aeruginosa, exhibited among the greatest levels of multi-drug resistance. Novel compound 1,10-phenanthroline-5,6-dione (phendione) shows promising antimicrobial activity, with MICs determined for all bacterial species, where levels of induced endotoxin varied depending on the concentration used. Tested biocide agents show potential to act as intermediate-level disinfectants in hospital settings, where all tested clinical isolates were susceptible to treatment.

Fungal skin infections and iatrogenic disease of companion animals continue to be an ongoing issue for veterinarians, where misdiagnosis or inapt medical treatment result in secondary conditions within animals. The widespread use of antifungals in both modern medicine and agriculture has resulted in concomitant resistance in species, where zoonotic transfer poses a risk to public health. Studies described herein assess the resistance of pathogenic species isolated from companion animals to a battery of conventional antimicrobial agents. Levels of resistance were detected using recognised in vitro methods, where additional novel therapeutic and biocide options were also extensively investigated. Results show high levels of resistance to the three main families of antifungal agents, namely caspofungin, Amp B and fluconazole. Resistance in Candida, Cryptococcal, Aspergillus and Trichophyton species is described herein, highlighting the need for defined species-specific antifungal breakpoints, and for Malassezia and Wickerhamomyces anomalus species which also have zoonotic potential. Novel compound phendione showed promising antimicrobial activity, with MICs determined for both fungal and bacterial species. The biocidal options investigated also showed potential to act as intermediate-level disinfectants, where peracetic acid proved most effective against fungal spore formers.