Health authorities worldwide continue to consider Salmonella as a major public health threat that causes 93.8 million foodborne infections with around 150,000 deaths annually each year. Such infections stand as major contributors to global expenses from foodborne diseases (EFSA., 2019; ECDC EFSA., 2022). Foodborne diseases persist considerably across Africa because of weak food safety structures that face regulatory limitations and outdated facilities. Grasping the factors that cause Salmonella throughout the food supply chain enables the creation of successful prevention measures (WHO, 2015). Salmonella contamination throughout Africa creates substantial healthcare risks for the population which result in recorded outbreaks that lead to hospital admissions and death alongside economic expenses (Ibrahim et al., 2018; Elafify et al., 2022). The lack of available resources and inadequate law enforcement continues to make complete control measures difficult which demonstrating the importance of establishing joint regional monitoring and support operations (Habib and Mohamed, 2022; Teklemariam et al., 2023).

Salmonella enterica is the main pathogenic member of the Enterobacteriaceae family and is one of the global leaders in causing bacterial gastroenteritis. Salmonellosis remains a serious public health concern across different European nations (Al-Gallas et al., 2022). The cellular invasion and survival of Salmonella bacteria inside macrophages represent an essential pathogenic process since it allows the bacteria to escape host immunity while remaining inside the host (Pinedo et al., 2022). The intracellular lifestyle of these bacteria creates diagnostic and therapeutic challenges because traditional treatment methods often fail to eliminate bacteria from intracellular reservoirs. Targeted intervention strategies aimed at intracellular survival mechanisms are essential to achieve effective outcomes for clinical capabilities and public health management of salmonellosis.

Bacterial virulence-related genes present in Salmonella efficiently initiate and accelerate the development of foodborne illnesses. The genetic elements give the pathogen the ability to adhere to host cells while breach tissues while escaping immune detection leading to increased infection potential (Vilela et al., 2020). The investigation of these genes represents a necessary step for the development of specific interventions to control Salmonella outbreaks and their prevention efforts. The need to grasp the molecular sequences that regulate bacterial aggression together with environmental stress paths is highlighted by such investigative work (Mohamed et al., 2022).

Experimental animal studies confirm Salmonella strains with specific virulence genes responsible for cellular attachment including intra-cellular survival present more hazardous infections, resulting in higher mortality than virulence-deficient strains (Khalefa et al., 2021; Hull et al., 2022; Mohamed et al., 2024). Salmonella Pathogenicity Islands (SPIs) genomic clusters increase experimental infection risks and lead to severe disease manifestations (Kombade and Kaur, 2021). Scientific studies of clinical microbial isolates have proven the existence of correlations between particular virulence marker occurrences and human cases of salmonellosis severity (Wang et al., 2020; Borah et al., 2022). The occurrence of the stn gene which produces enterotoxin is associated with higher hospitalization rates and more severe clinical expressions in patients (Nikiema et al., 2021).

Advances in whole-genome sequencing (WGS), a method that determines the complete DNA sequence of an organism's genome at a single time, have facilitated detailed analysis of the genetic features that underpin Salmonella virulence. By examining the complete genomes of various isolates, scientists have been able to map the distribution and frequency of virulence genes across different strains, shedding light on their role in disease severity and immune evasion (Mohamed et al., 2025). The genomic findings validate previous research demonstrating that particular genetic patterns relate to infections that spread deeply into the body and resist treatment (Nikiema et al., 2021). Additionally, functional genomics approaches including gene knockouts and expression analysis in both in vitro and ex vivo models have proven instrumental in clarifying the specific contributions of individual virulence genes to pathogenesis. These experimental frameworks not only validate the importance of these genes in promoting Salmonella infection but also help assess their role in determining clinical outcomes (Lozano-Villegas et al., 2023).

Some genetic virulence components missing in Salmonella isolates from food sources diminish their ability to produce clinical salmonellosis (Wang et al., 2020). The virulence genes produce proteins that help bacteria establish residence and invade host cells. These microbe strains become less pathogenic because of their absence or reduced expression levels of essential virulence genes (Vilela et al., 2020). Ingestion of bacteria with lower virulence often results in mild or no apparent symptoms in human bodies. Organisms that lack necessary virulence factors demonstrate a reduced ability to spread in human digestive tracts which decreases the chance of infections after contact with contaminated material (Wang et al., 2020). The health risk potential of foodborne Salmonella strains originates from the virulence genes that they contain or lack. Detecting genetic markers serves vital functions for both danger evaluation in public health and intervention development for foodborne infection control (Habib et al., 2023b; Oueslati et al., 2023).

The pathogenic capabilities of Salmonella species result from virulence genes that exist as Salmonella Pathogenicity Islands (SPIs) throughout the bacterial chromosome (Dougnon et al., 2017). The five classified SPIs provide essential knowledge to scientists and SPI-1 along with SPI-2 stand out because they encode the Type III secretion systems (T3SSs) (Cerny and Holden, 2019; Lerminiaux et al., 2020). The interaction between SPI-1 and SPI-2 demonstrates different functions because SPI-1 enables cell invasion and triggers inflammation whereas SPI-2 drives phagocytic cell survival across the body (Wemyss and Pearson, 2019). The genetic construct invA within SPI-1 exists across all Salmonella strains because it serves as the critical factor for host cell penetration. The spiC gene encoded by SPI-2 produces essential secretion system components required for virulence while operating independently from flagellar structures (Hasan, 2021; Wang et al., 2021). Both SPI-3 and SPI-4 exist throughout all Salmonella lineages however, the patterns of occurrence for SPI-4 and SPI-5 remain uncertain (Wang et al., 2020). SPI-4 contributes to early interactions with intestinal epithelial cells and supports long-term colonization, including the orfL gene linked to survival within macrophages (Albanwawy and Abdul-Lateef, 2021). SPI-5 is involved in multiple stages of the infection process, with pipD playing a notable role (Wang et al., 2020). Additionally, Salmonella harbors extra-chromosomal virulence determinants such as the Salmonella virulence plasmid (spvRABCD), which enhances systemic dissemination and enables replication at extraintestinal sites (Dougnon et al., 2017; Hsu et al., 2019). Polyamines, which are present in elevated concentrations in various fermented, aged, and plant-derived foods, serve critical functions in cellular homeostasis and microbial viability. In the context of foodborne pathogens such as Salmonella, elevated dietary polyamine levels may enhance bacterial resilience within the gastrointestinal tract, potentially contributing to heightened virulence and persistence during infection. This association suggests that polyamines may play a significant role in modulating pathogen-host interactions. Therefore, elucidating the link between polyamine concentrations in food and microbial pathogenicity is essential for informing targeted strategies aimed at mitigating foodborne illnesses and safeguarding public health (Mohamed et al., 2019a; Krysenko and Wohlleben, 2022).

This review noted that Salmonella enterica's infection mechanisms in Eastern and Southern Africa are driven primarily by the common invA gene, as well as by different secondary factors such as the plasmid-borne spv operon, typhoid toxin genes, adhesion proteins such as bapA, and stress-related loci such as pagC and mgtB, among others. High carriage rates of spv in Ethiopia's dairy chain, Tanzanian backyard poultry, and Zimbabwean outbreak strains underscore its pivotal role in systemic disease. Whole-genome data from South Africa reveal even broader repertoires that vary with production intensity and ecological niche. Fresh-produced isolates in Botswana and reptile reservoirs in Limpopo further illustrate how fully virulent strains move beyond traditional livestock pathways. Nonetheless, surveillance is not complete since using single-gene PCR panels fails to detect hybrids and certain plasmid fragments. This finding suggests these isolates have other, yet unidentified, ways to cause disease. By applying these results, researchers should regularly keep watch over the genetic makeup, monitor the sharing of plasmid resistance, and prepare different strategies to address it. For this reason, knowledge of the source is vital for planning steps like improving the cold chain and reptile management.