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Antimicrobial resistance (AMR) in livestock production systems has emerged as a major global health concern, threatening not only animal welfare and agricultural productivity but also food safety and public health. The widespread, and often poorly regulated, use of antimicrobials for growth promotion, prophylaxis, and metaphylaxis has accelerated the emergence and dissemination of resistant bacteria and resistance genes. These elements circulate across interconnected animal, environmental, and human ecosystems, driven by mobile genetic elements and amplified through the food production chain. It is estimated that more than two-thirds of medically important antimicrobials are used in animals, and AMR could cause millions of human deaths annually by mid-century if unchecked. In some livestock systems, multidrug-resistant E. coli prevalence already exceeds half of isolates, particularly in poultry and swine in low- and middle-income countries (LMICs). This narrative review provides a comprehensive overview of the molecular epidemiology, ecological drivers, and One Health implications of AMR in food-producing animals. We highlight key zoonotic and foodborne bacterial pathogens—including Escherichia coli, Salmonella enterica, and Staphylococcus aureus—as well as underappreciated reservoirs in commensal microbiota and livestock environments. Diagnostic platforms spanning phenotypic assays, PCR, MALDI-TOF MS, whole-genome sequencing, and CRISPR-based tools are examined for their roles in AMR detection, surveillance, and resistance gene characterization. We also evaluate current antimicrobial stewardship practices, global and regional surveillance initiatives, and policy frameworks, identifying critical implementation gaps, especially in low- and middle-income countries. Emerging sectors such as aquaculture and insect farming are considered for their potential role as future AMR hotspots. Finally, we outline future directions including real-time genomic surveillance, AI-assisted resistance prediction, and integrated One Health data platforms as essential innovations to combat AMR. Mitigating the threat of AMR in animal agriculture will require coordinated scientific, regulatory, and cross-sectoral responses to ensure the long-term efficacy of antimicrobial agents for both human and veterinary medicine.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become one of the most serious problems confronting modern healthcare, particularly in intensive care units where patients are highly susceptible, procedures are frequent, and antibiotic exposure is often prolonged. In this review, carbapenem resistance in K. pneumoniae is presented not as a fixed feature of individual bacteria, but as a process that is constantly changing and closely interconnected. We bring together evidence showing how the spread of successful bacterial lineages, the exchange of resistance genes, and gradual genetic adjustment combine to drive both the rapid spread and the long-lasting presence of resistance. A major focus is placed on mobile genetic elements, including commonly encountered plasmid backbones, transposons, and insertion sequences that carry carbapenemase genes such as blaKPC, blaNDM, and blaOXA-48-like. These elements allow resistance genes to move easily between bacteria and across different biological environments. The human gut plays a particularly important role in this process. Its microbial community serves as a largely unseen reservoir where resistance genes can circulate and accumulate well before infection becomes clinically apparent, making prevention and control more difficult. This review also discusses the key biological factors that shape resistance levels, including carbapenemase production, changes in the bacterial cell membrane, and systems that expel antibiotics from the cell, and explains how these features work together. Advances in molecular testing have made it possible to identify resistance more quickly, supporting earlier clinical decisions and infection control measures. Even so, current tests remain limited by narrow targets and may miss low-level carriage, hidden genetic reservoirs, or newly emerging resistance patterns. Finally, we look ahead to approaches that move beyond detection alone, emphasizing the need for integrated surveillance, thoughtful antibiotic use, and coordinated system-wide strategies to lessen the impact of CRKP.

Livestock-associated Staphylococcus species—particularly Staphylococcus aureus (S. aureus), Staphylococcus pseudintermedius (S. pseudintermedius), and coagulase-negative staphylococci (CoNS)—pose escalating threats to animal health, food safety, and public health due to their evolving antimicrobial resistance (AMR) profiles. This review synthesizes recent insights into the molecular epidemiology, resistance determinants, and host adaptation strategies of these pathogens across food-producing animals. We highlight the role of mobile genetic elements (MGEs), clonal dissemination, and biofilm formation in shaping multidrug resistance (MDR) patterns. Diagnostic advancements, including MALDI-TOF MS, whole-genome sequencing (WGS), and PCR-based assays, are discussed alongside treatment challenges arising from therapeutic failures and limited vaccine efficacy. The review critically examines current AMR surveillance gaps and the need for integrative One Health frameworks that encompass animals, humans, and the environment. Novel tools such as metagenomics, real-time genomic surveillance, and artificial intelligence (AI)-driven analytics are proposed to enhance predictive monitoring and resistance management. Together, these insights underscore the urgency of coordinated, evidence-based interventions to curb the spread of MDR staphylococci and safeguard One Health.

Antimicrobial resistance (AMR) remains a major clinical challenge, with Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) accounting for a substantial share of multidrug-resistant (MDR) infections worldwide. These organisms undermine antibiotic efficacy through reduced permeability, surface shielding, biofilm formation, and rapid genetic adaptation, mechanisms that primarily restrict effective exposure at infection sites. Bacteriophages, phage-derived enzymes, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based antimicrobials provide selective and mechanistically distinct alternatives to conventional antibiotics, but their performance in vivo is often limited by instability in physiological environments, immune neutralization, uneven tissue distribution, and insufficient access to bacteria protected by biofilms or surface-associated barriers. This narrative review examines how nanotechnology-based delivery systems can address these constraints. We first outline the delivery-relevant biological barrier characteristic of ESKAPE pathogens, then summarize the therapeutic potential and inherent limitations of whole phages, phage-derived enzymes, and CRISPR-based antimicrobials when used without formulation. Major nanotechnology platforms for antibacterial delivery are reviewed, followed by analysis of how nano-enabled systems can improve stability, localization, and persistence of these biological agents. A pathogen-aware integration framework is presented that links dominant barriers in each ESKAPE pathogen to the biological modality and nano-enabled delivery strategy most likely to enhance exposure at infection sites. Translational challenges, regulatory considerations, and emerging directions, including responsive delivery systems and personalized approaches, are also discussed. Overall, nano-enabled phage-based therapeutics represent a realistic and adaptable strategy for managing MDR ESKAPE infections. Therapeutic success depends on both continued discovery and engineering of antibacterial agents and effective delivery design.

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact.

Acinetobacter baumannii is widely recognized as a problematic pathogen in healthcare settings due to its ability to acquire resistance to multiple antimicrobial agents. However, less attention has been given to its presence outside hospitals. In this cross-sectional, laboratory-based surveillance study, we investigated the occurrence of A. baumannii in ready-to-eat (RTE) foods sold at retail outlets in four cities of the Al-Qassim region, Saudi Arabia, during a single season. A total of 240 RTE food samples were analyzed using culture-based and molecular approaches for species confirmation, and antimicrobial susceptibility profiles were determined. A. baumannii was identified in 19 samples (7.9%), spanning several food categories. Most isolates showed resistance to multiple antimicrobial classes, and 16 met the criteria for multidrug resistance (MDR). Among the confirmed isolates, blaOXA-23-like was detected in 16 (84.2%), blaOXA-24/40-like in 2 (10.5%), and blaOXA-58-like in 1 (5.3%). Resistance to fluoroquinolones, tetracyclines, and aminoglycosides was common, and OXA-type carbapenemase genes were detected in 16 isolates. These findings indicate that RTE foods can represent non-clinical environments in which MDR A. baumannii may be detected. Including food sources in antimicrobial resistance surveillance may therefore strengthen our understanding of the ecology of this pathogen within a One Health framework.

Food systems expose bacteria to repeated nonlethal stresses during primary production, processing, storage, and sanitation. Depending on the type, intensity, and sequence of exposure, these stresses may weaken cells, act synergistically to promote inactivation, or fail to eliminate contamination. Instead, they can alter bacterial physiology in ways that affect survival, recovery, detection, and responses to control measures. This review examines how stress history contributes to persistent food safety challenges. Listeria monocytogenes is used as a central biological model, with relevant comparisons to other foodborne pathogens. Evidence from food-processing and environmental studies shows that repeated sublethal stress can shift bacterial populations toward stress-hardened states. Here, “stress-hardened” refers to reversible physiological changes and the survival of more tolerant cells, not permanent genetic adaptation. These states include sublethal injury, delayed growth, viable but nonculturable cells, biofilm formation, and increased tolerance to later stresses. These outcomes contribute to, but do not fully explain, the persistence of L. monocytogenes in food environments; intrinsic traits such as psychrotrophic growth and interactions with endogenous microflora also play important roles. These factors help explain repeated recovery of L. monocytogenes after sanitation and the underestimation of viable cells by routine culture-based methods, which do not reliably indicate whether pre-stressed cells retain the potential to cause foodborne illness. Many monitoring and validation approaches rely on unstressed laboratory cultures and fixed enrichment protocols. These conditions do not reflect the physiological states encountered in real food systems. As a result, negative test results may reflect limited recovery rather than true absence, and control performance may be overestimated when stress-conditioned populations are not considered. Across the farm-to-fork continuum, stress responses, persistence mechanisms, and detection limitations are closely linked, indicating that stress history should be considered a core element of hazard characterization, monitoring, and control validation. Incorporating stress biology into food safety assessment can improve the realism of verification strategies when combined with risk characterization that considers infectious dose and host susceptibility, and support control strategies under real-world processing and environmental conditions.

Background: Fluoroquinolone (FQ) resistance in Escherichia coli (E. coli) undermines empiric therapy and often coincides with multidrug resistance (MDR). Because sequencing is not routinely available in many laboratories, we evaluated a phenotype-first, sequencing-independent diagnostic framework deployable on standard platforms. Methods: We profiled 45 archived E. coli isolates for susceptibility (Clinical and Laboratory Standards Institute [CLSI]-guided), extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase (AmpC) phenotypes, MDR, and multiple-antibiotic resistance (MAR) indices. Ten founders (five FQ-susceptible [FQ-S], five low-level resistant [LLR]) seeded 20 parallel lineages exposed to stepwise ciprofloxacin. We tracked minimum inhibitory concentrations (MICs), collateral resistance, growth kinetics, and biofilm biomass using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification, automated and reference antimicrobial susceptibility testing (AST), growth-curve analysis, and crystal violet microtiter assays. The intended use is a sequencing-independent workflow for routine laboratories—especially where whole-genome sequencing is not readily available—working with archived or prospective clinical E. coli. This workflow is best applied when local FQ nonsusceptibility threatens empiric reliability; inputs include standard ID/AST with simple growth and biofilm assays. Primary outputs include: (i) MIC trajectories with time to high-level resistance (HLR), (ii) ΔMAR-summarized collateral resistance with class-level susceptible-to-resistant conversions, and (iii) concise fitness/biofilm summaries to guide empiric-policy refresh and early de-escalation. Results: At baseline, ciprofloxacin nonsusceptibility was 40.0%; ESBL and AmpC phenotypes were confirmed in 28.9% and 15.6%, respectively; 46.7% met the MDR definition; and the median MAR index was 0.29. During evolution, 70% of lineages reached HLR (MIC ≥ 4 μg/mL), with earlier conversion from LLR versus FQ-S founders (median 7 vs. 11 passages). Collateral resistance emerged most often to third-generation cephalosporins (3GCs), trimethoprim–sulfamethoxazole, and tetracyclines, while carbapenem activity was preserved. MAR increased in parallel with rising MICs. Resistance acquisition imposed modest fitness costs (slightly reduced growth rates and longer lag phases) that were partly offset under subinhibitory ciprofloxacin, whereas biofilm biomass changed little. Conclusions: this phenotype-first, routine-laboratory workflow rapidly maps FQ resistance and clinically relevant co-selection in E. coli. In high-resistance settings, empiric FQ use is difficult to justify, and MAR trends provide practical co-selection signals for stewardship. This reproducible framework complements genomic surveillance and is directly applicable where sequencing is unavailable.

Preventive immunology is emerging as a cornerstone of animal infectious disease control within One Health, shifting emphasis from treatment to prevention. This review integrates mechanistic insights in host immunity with a comparative evaluation of next-generation interventions—mRNA/DNA and viral-vector vaccines, nanovaccines, monoclonal antibodies, cytokine modulators, probiotics/postbiotics, bacteriophages, and CRISPR-based approaches—highlighting their immunogenicity, thermostability, delivery, and field readiness. Distinct from prior reviews, we appraise diagnostics as preventive tools (point-of-care assays, biosensors, MALDI-TOF MS, AI-enabled analytics) that enable early detection, risk prediction, and targeted interventions, and we map quantifiable links between successful prevention and reduced antimicrobial use. We embed translation factors—regulatory alignment, scalable manufacturing, workforce capacity, equitable access in LMICs, and public trust—alongside environmental and zoonotic interfaces that shape antimicrobial resistance dynamics. We also provide a critical analysis of limitations and failure cases: gene editing may require stacked edits and concurrent vaccination; phage programs must manage host range, resistance, stability, and regulation; and probiotic benefits remain context-specific. Finally, we present a risk–benefit–readiness framework and a time-bound research agenda to guide deployment and evaluation across animal–human–environmental systems. Coordinating scientific innovation with governance and ethics can measurably reduce disease burden, curb antimicrobial consumption, and improve health outcomes across species.

Ready-to-eat (RTE) foods can carry antimicrobial-resistant pathogens; however, few studies link real-world surveillance to practical interventions. This study addressed this gap by estimating the prevalence of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) in ready-to-eat foods from Al-Qassim and evaluating a rapid, orthogonal confirmation workflow (culture → MALDI-TOF MS → Vitek 2 → mecA/mecC PCR). The in vitro activity of citrate-stabilized silver nanoparticles (AgNPs) against food-derived MRSA was quantified, and synergy with oxacillin (primary) and ciprofloxacin (secondary) was examined. Silver-susceptibility stability was assessed over 20 days of sub-MIC serial passage, with attention to whether β-lactam co-exposure constrained drift. We surveyed 149 RTE products and paired the confirmation workflow with mechanistic tests of AgNPs as antibiotic adjuvants. S. aureus was recovered from 24.2% of products and MRSA from 6.7%, with higher recovery from animal-source matrices and street-vendor outlets. MALDI-TOF MS provided rapid species confirmation and revealed two reproducible low-mass peaks (m/z 3990 and 4125) associated with MRSA, supporting spectral triage pending molecular confirmation. Antimicrobial susceptibility testing showed the expected β-lactam split (MRSA oxacillin/cefoxitin non-susceptible; MSSA oxacillin-susceptible but largely penicillin-resistant), with last-line agents retained. Citrate-stabilized AgNPs displayed consistent potency against food-derived MRSA (MIC 8–32 µg/mL; MIC50 16; MIC90 32) and were predominantly bactericidal (MBC/MIC ≤ 4 in 90%). Checkerboards demonstrated frequent AgNP–oxacillin synergy (median fractional inhibitory concentration index [FICI] 0.37; 4–16-fold oxacillin MIC reductions) and additive-to-synergistic effects with ciprofloxacin (median FICI 0.63), translating time–kill assays into rapid, sustained bactericidal activity without antagonism. During sub-MIC evolution, silver MICs rose modestly (median two-fold) and often regressed off drug; oxacillin co-exposure limited drift. RTE foods therefore represent credible MRSA exposure routes. Integrating MALDI-assisted triage with automated AST enables scalable surveillance, and standardized AgNP formulations emerge as promising β-lactam adjuvants—pending in situ efficacy, safety, and residue evaluation.