Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 25, Issue 3, 2025

SNP based association studies have revolutionized the field of biomedicines. Enteric fever is a systemic disease with etiologic agent Salmonella enterica serovar typhi and paratyphi. It is a serious health issue worldwide and presents wide variations in incidence, rates, and severity. Previous investigations revealed that genetic variations may lead to susceptibility to typhoid fever. The current study was performed to investigate the potential association of PARK2_e01(−697) polymorphism with the susceptibility to typhoid in the Punjabi population.

For this case-control study, blood samples obtained from typhoid patients with positive Typhidot or blood culture test (n=72) and healthy controls (n=73) were processed for DNA extraction. The polymorphism PARK2_e01(-697) analysis was carried out by using PCR and RFLP.

No allelic association was found between PARK2_e01(-697) and susceptibility to typhoid fever in the understudy population.

This case control study is the demonstration of the non-association of PARK2_e01(-697) with typhoid in the Pakistani population. Future research, using larger population size, will help to elucidate the role of PARK2_e01(-697) polymorphism in typhoid pathogenesis.

Clostridium difficile is an opportunistic infection that can lead to antibiotic-associated diarrhea and toxic megacolon.

This systematic review study aimed to investigate polyphenols' antibacterial and anti-toxin properties and their effects on reducing complications related to C. difficile Infections (CDI).

This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions.

Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Factor-α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) levels, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of C. difficile more difficult and prevent it from producing toxins. Furthermore, polyphenols can exhibit prebiotic properties, promoting the growth of beneficial Bifidobacterium and Lactobacillus species and consequently regulating gut microbiota, exerting antimicrobial activities against C. difficile. They also induce their beneficial effects by inhibiting the production of C. difficile TcdA and TcdB.

Polyphenols have been reported to inhibit C. difficile growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans.

The alarming increase in antibiotic resistance urges alternative and efficacious antimicrobial solutions. Historically, medicinal plants have been used for therapeutic purposes, such as relieving pain and healing wounds. The evaluation of the natural therapeutic effects of medicinal plants in a manner that resembles how humans typically consume them is lacking. In this study, many medicinal plants known to have some antimicrobial effects, including Frankincense, Garlic, Myrrh, and Ginger, were evaluated for their direct antibacterial activity in raw form.

The direct antimicrobial activity of medicinal plants was evaluated against a variety of Gram-positive and Gram-negative bacterial strains, such as Staphylococcus aureus (S. aureus.), Acinetobacter baumannii and Klebsiella pneumoniae using agar well diffusion method and turbidity measurements in suspension culture.

Out of all the tested medicinal plants, only raw garlic (Allium sativum) powder, when dissolved in water or vinegar, offered a straightforward antibacterial activity. A combination of garlic extract and vinegar increased antibacterial activity. Aqueous garlic extracts displayed robust antimicrobial activity against many resistant bacteria. Other medicinal plants used in this study had absent or minimal antibacterial effects.

Only garlic in its raw form was effective against antibiotic-resistant bacteria. The increase in the antibacterial activity of garlic when combined with vinegar suggests synergistic activity of garlic. The straightforward antibacterial action of raw garlic may be strategically harnessed to combat the continuous challenge of increasing antibiotic resistance. This work promotes additional testing of more natural products (in raw form) and assesses their therapeutic effects clinically.

Toxoplasmosis is a cosmopolitan infectious disease in warm-blooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines.

The purpose of this study was to design a multi-epitope vaccine using several bioinformatics approaches against the antigens of Toxoplasma gondii (T. gondii).

Three proteins of T. gondii, including ROP18, MIC4, and SAG1 were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical properties, secondary and tertiary structure, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers.

RMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein contained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, evaluation of antigenicity and allergenicity showed the protein to be an immunogen and non-allergen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions respectively. ΔG of the best-predicted mRNA secondary structure was −593.80 kcal/mol which indicates a stable loop is not formed at the 5′ end. .

Finally, the accuracy and precision of the in silico analysis must be confirmed by successful heterologous expression and experimental studies.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tuberculous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system.

In this work, ligands having improved BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules.

In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase β of Mycobacterium tuberculosis.

The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

The current study aimed to formulate and evaluate herbal gels containing essential oils for the treatment of infection caused by microbial species, i.e., S. aureus, E. coli, P. aeruginosa, and B. subtilis. These species are also responsible for acne directly and indirectly.

The gels were prepared using a gelling agent with 1% Carbopol-940, and they were further evaluated for physical appearance, drug content, in-vitro drug release, viscosity, extrudability, pH, and spreadability. Further, anti-microbial screening was done with various microbial species.

Studies revealed that the gel was highly effective against the selected species except for the fungal strain. ZOI was observed ranging from 3.1 ± 0.01 mm to 13.4 ± 0.14 mm. The maximum ZOI was observed at 13.4 ± 0.14 mm against S. aureus. The physical properties of the gel satisfied the standard parameters.

The prepared herbal gel was found to have highly promising activity against bacterial species associated with bacterial infection but in a dose-dependent manner. However, more research is required.