S. typhimurium LPS

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a significant Gram-negative pathogen, widely found in animals and capable of being transmitted to humans through contaminated food and water, causing foodborne diseases. As one of the common pathogens responsible for human intestinal infections, S. Typhimurium primarily causes gastroenteritis and diarrhea, and in some cases, can lead to systemic diseases. Its transmission is mainly through the food chain, especially contaminated meat, dairy products, eggs, making it one of the most critical global foodborne pathogens. Each year, approximately 200 million people worldwide are infected with Salmonella, resulting in over 60,000 deaths, with S. Typhimurium being one of the most common serotypes. These infections are often closely related to animal-derived foods such as poultry, pork, beef, and dairy products. In China, foodborne illnesses caused by S. Typhimurium contamination in dairy products such as milk are particularly concerning. With the increase in international trade, the cross-border circulation of contaminated food has further heightened the risk of S. Typhimurium transmission. Therefore, effectively monitoring and controlling the spread of S. Typhimurium has become a critical global public health issue. Although traditional plate culture methods are widely used for the detection of S. Typhimurium, their cumbersome operation and lengthy processing time limit large-scale application. To address this challenge, modern detection technologies have been continuously innovated. Methods such as polymerase chain reaction (PCR) and surface plasmon resonance have significantly improved detection efficiency. However, these technologies often require expensive equipment and professional personnel, making them difficult to promote in resource-limited regions. Therefore, emerging technologies such as electrochemical immunosensors, which are simple to operate, highly sensitive, and specific, are gradually becoming a research focus. These technologies work by fixing antibodies on the electrode surface that bind to the S. Typhimurium antigen, generating measurable electrochemical signals, greatly improving the efficiency of pathogen detection.

Over the past century, the invention and application of antibiotics have drastically reduced the mortality rate from bacterial infections. However, with the emergence of antibiotic-resistant S. Typhimurium strains, the effectiveness of antibiotics is facing severe challenges. Antibiotic resistance (AMR) refers to the ability of bacteria to resist the effects of antibiotics through mutations or acquisition of external genes, rendering previously effective drugs ineffective. S. Typhimurium resistance to common antibiotics such as fluoroquinolones, chloramphenicol, and ampicillin has been observed in many countries, especially in developing nations. The antibiotic resistance of S. Typhimurium is achieved through multiple mechanisms, including the increase in efflux pumps, changes in cell membrane permeability, modification of antibiotic targets, and the formation of biofilms. Biofilms, as protective outer shells of bacteria, can effectively resist external pressures, including attacks from antibiotics. Studies have shown that S. Typhimurium biofilms contain components such as cellulose, O-antigen, and extracellular DNA, which not only enhance bacterial resistance but also complicate treatment. Therefore, targeting biofilm disruption has become an important goal in antibiotic resistance research. Of particular concern is the rapid rise of a monophasic variant of S. Typhimurium (1,4,[5],12:i:-) over the past two decades. This variant not only spreads widely among animals, especially in pig populations, but can also infect humans through the food chain. The multi-drug resistance (MDR) characteristic of the monophasic variant has raised significant concern in public health. Whole-genome sequencing (WGS) technology has revealed the widespread transmission pathways of this strain and its close association with antimicrobial resistance genes. The rapid spread of this emerging serotype not only exacerbates the problem of antibiotic resistance but also renders traditional antibiotic treatment strategies increasingly ineffective. As resistance to quinolones and cephalosporins increases, treatment options for S. Typhimurium infections are becoming more limited. In countries like Pakistan, large-scale outbreaks caused by the monophasic variant have rendered multiple antibiotics ineffective, forcing clinicians to resort to more expensive third-line drugs such as tigecycline and carbapenems.

Figure 1. Innate immune response of the stomach to Salmonella (Source: Broz P, et al., 2012)

The ability of S. Typhimurium to survive and proliferate in the host is largely due to its strategies to counteract host immune responses. The host's innate immune system attempts to inhibit pathogen invasion through multiple defense mechanisms, such as intestinal mucus and antimicrobial peptides. However, S. Typhimurium has evolved a series of mechanisms to evade these defenses. For example, it can penetrate the intestinal mucus layer to directly contact epithelial cells, thereby initiating infection. Additionally, S. Typhimurium utilizes structures such as flagella and secretion systems to inhibit the host's immune response, allowing long-term survival within the body. Research has found that S. Typhimurium not only causes acute gastroenteritis but can also persist in the host through persistent infection (PI), even surviving asymptomatically during the host's adaptive immune response. This mechanism of persistent infection is closely related to the formation of persistent antibiotic-resistant populations that survive antibiotic treatment and resume proliferation once environmental pressure is relieved, further complicating the infection. Globally, antibiotic resistance has had a severe negative impact on public health systems, particularly in developing countries where limited medical resources and antibiotic misuse exacerbate the resistance problem. The rapid spread of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhimurium strains has posed unprecedented challenges to traditional antibiotic treatment. The failure of combination therapy and the continuous emergence of new resistant strains have prompted scientists to accelerate the development of new antimicrobial drugs.

Figure 2. Determinants of antimicrobial responses to Salmonella Typhi (Source: Chowdhury AR, et al., 2024)

Salmonella typhimurium lipopolysaccharide
LPS from Salmonella typhimurium
S. typhimurium LPS