Antimicrobial resistance (AMR) is presented as a defining global health crisis in this review, with a projected burden reaching 1.91 million deaths per year by 2050. The authors call for a comprehensive approach that examines both the molecular strategies bacteria use to evade antibiotics and the social, economic and structural drivers that facilitate the emergence and spread of resistance. They emphasize that technical solutions alone are unlikely to achieve durable control of AMR without integrating social context.
The review categorizes bacterial resistance mechanisms into broad biological classes operating at genotypic and phenotypic levels. Understanding these mechanisms is framed as essential for identifying new therapeutic targets and informing design of next-generation antibiotics or adjunctive strategies.
Genotypic mechanisms produce inheritable changes in bacterial populations. These include acquisition or mutation of genetic elements that encode resistance determinants, enabling stable transmission of resistance traits across generations and between strains. The authors underscore that genotypic adaptations are central to the long-term dissemination of resistance and therefore are primary targets when seeking to block spread through surveillance, stewardship and novel drug development.
Phenotypic mechanisms encompass non-inheritable, often reversible adaptations—such as changes in cell physiology or structure—that transiently reduce antibiotic susceptibility. These adaptations can include biofilm formation, altered metabolic states, or inducible stress responses that confer temporary protection. Because phenotypic resistance can allow survival under antibiotic exposure and promote subsequent genetic evolution, characterizing these states expands opportunities for therapeutic intervention beyond classical genetic targets.
A deeper mechanistic understanding of both genotypic and phenotypic resistance can reveal novel molecular targets and inform the development of new antibiotic classes or adjuvants that circumvent or suppress resistance pathways. The review advocates prioritizing such mechanistic research but stresses that discovery and deployment of new agents must be integrated with strategies addressing the social contexts that drive misuse and transmission.
Alongside biological mechanisms, the review highlights several socio-structural factors that play critical roles in the development and dissemination of AMR. The authors argue that occupational exposures, economic inequities and gendered social roles contribute to patterns of antibiotic access, informal use, and differential exposure to resistant pathogens. Addressing these determinants is essential to reduce selective pressures that favor resistant organisms and to limit opportunities for spread.
Workplace and livelihood contexts can increase contact with resistant organisms or environments where antibiotics are used extensively (for example, in agriculture or informal healthcare settings). The review points to occupationally driven exposures and practices as drivers of informal antibiotic use and transmission, suggesting targeted interventions in high-risk occupations are needed.
Economic disparities affect access to formal healthcare, diagnostic services, and regulated antibiotic supplies. Where formal access is limited, informal channels and self-medication may prevail, increasing inappropriate antibiotic consumption and selective pressure for resistance. The review highlights the need to consider economic structures when designing stewardship and access interventions.
Gendered social roles can shape who is exposed to resistant pathogens and who manages antibiotic use within households or communities. The authors note that these roles influence informal antibiotic practices and exposure pathways, and therefore should be considered in socially sensitive AMR strategies.
The review argues for integrating biological insights with social and structural analyses to create a comprehensive, socially grounded roadmap for AMR interventions. It situates this integrated perspective within a One Health framework that recognizes interconnected human, animal and environmental drivers. The authors propose that combining mechanistic understanding of bacterial resistance with interventions addressing occupational, economic and gendered determinants will be more effective than technical solutions alone.
The central conclusion is that combating AMR requires a dual-lens strategy: continue discovery of new antimicrobial agents and targets informed by genotypic and phenotypic mechanisms, while simultaneously implementing socially informed policies and interventions to reduce misuse, exposure and transmission. The review emphasizes that ignoring social determinants will limit the impact of technical innovations and that a coordinated One Health approach is necessary to produce sustainable results.
The authors declare no known competing financial interests or personal relationships that could have influenced the work reported in this paper.