Salmonella enterica subsp. enterica serovar Typhi

Salmonella enterica subsp. enterica serovar Typhi

1. Introduction to Salmonella enterica subspecies enterica serovar Typhi

Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) is a Gram-negative, rod-shaped bacterium that belongs to the family Enterobacteriaceae. It is the causative agent of typhoid fever, a systemic illness that primarily affects humans and is transmitted via the fecal-oral route. S. Typhi is a highly adapted human pathogen that does not typically infect animals, which distinguishes it from other Salmonella serovars. Its virulence is associated with several factors, including its ability to invade the intestinal epithelium, survive in macrophages, and evade the immune system (Bäumler et al., 2018).

2. Taxonomy and Classification

Domain: Bacteria

Phylum: Proteobacteria

Class: Gammaproteobacteria

Order: Enterobacterales

Family: Enterobacteriaceae

Genus: Salmonella

Species: Salmonella enterica

Subspecies: enterica

Serovar: Typhi

3. Morphological Characteristics

Shape: S. Typhi is a Gram-negative, straight rod (0.7–1.5 µm in diameter and 2.0–5.0 µm in length).

Arrangement: Single or in pairs; can form short chains.

Motility: Motile due to the presence of peritrichous flagella. This flagellation is important for its ability to move through the intestinal mucosa.

Capsule: S. Typhi has a capsular structure made of Vi antigen, which helps the bacterium evade host immune responses by preventing phagocytosis (MacLennan et al., 2014).

4. Cultural Characteristics

Salmonella enterica subsp. enterica serovar Typhi grows well on a variety of selective and differential media in laboratory settings. The cultural characteristics of S. Typhi can be used to distinguish it from other Salmonella serovars and enteric pathogens.

Growth Temperature: S. Typhi is a mesophilic organism, with optimal growth between 37°C and 42°C. It can grow within a temperature range of 15°C to 43°C, making it suitable for growth in both environmental and clinical conditions (Veldman et al., 2019).

Oxygen Requirements: Facultatively anaerobic, allowing it to grow in the presence or absence of oxygen.

Colony Morphology: On solid media, S. Typhi colonies are typically:

On MacConkey agar: S. Typhi does not ferment lactose, resulting in pale or colorless colonies. This feature is important for distinguishing Salmonella from lactose-fermenting organisms like Escherichia coli.

On Salmonella-Shigella (SS) agar: Colonies appear as colorless or pale due to the non-fermentation of lactose, but hydrogen sulfide (H₂S) production may result in black centers in colonies.

On Xylose Lysine Deoxycholate (XLD) agar: Colonies are typically yellow with black centers due to the production of H₂S, which reacts with the iron salts in the media (Zhu et al., 2021).

On Brilliant Green Agar: S. Typhi produces red colonies, which helps distinguish it from other enteric pathogens.

Pigmentation: Unlike many Salmonella strains, S. Typhi does not produce characteristic pigments, which distinguishes it from other serovars like S. enterica serovar Paratyphi.

5. Biochemical Characteristics

Salmonella Typhi exhibits distinct biochemical characteristics that aid in its laboratory identification. Some key tests include:

Catalase: Positive; produces bubbles when hydrogen peroxide is added.

Oxidase: Negative; this differentiates S. Typhi from oxidase-positive organisms like Pseudomonas spp.

Lactose Fermentation: Negative; S. Typhi is non-lactose fermenting, which distinguishes it from E. coli and other lactose fermenters.

Indole Test: Negative; S. Typhi does not produce indole from tryptophan.

Urease Test: Negative; S. Typhi does not hydrolyze urea.

H₂S Production: Positive; produces hydrogen sulfide, visible as black precipitates on XLD and SS agars.

Citrate Utilization: Negative; does not utilize citrate as the sole carbon source.

Triple Sugar Iron (TSI) Test: S. Typhi typically produces an alkaline slant and acid butt with H₂S production, forming a black precipitate (Bäumler et al., 2018).

6. Virulence Factors

Several virulence factors contribute to the pathogenicity of S. Typhi, enabling it to invade the human host, evade immune defenses, and cause systemic illness:

Vi Capsule (Virulence Antigen): The Vi antigen is a polysaccharide capsule that allows the bacterium to evade host immune defenses by preventing phagocytosis and inhibiting complement activation. It also helps the pathogen survive in macrophages (Mastroeni et al., 2009).

Type III Secretion System (T3SS): This system allows S. Typhi to inject virulence proteins into host cells, promoting intracellular survival and dissemination.

Endotoxins (Lipopolysaccharide): The lipid A component of the lipopolysaccharide (LPS) is an endotoxin that induces a strong immune response, contributing to fever, septicemia, and inflammatory responses during infection (Jiang et al., 2016).

Flagella: The motility provided by flagella aids in penetration of mucosal surfaces and movement within the gastrointestinal tract.

Salmonella Pathogenicity Islands (SPIs): These genomic islands harbor genes responsible for invasion and survival within the host. SPIs, such as SPI-1 and SPI-2, are critical for the bacteria’s ability to invade intestinal epithelial cells and survive within phagocytes (Hershberg et al., 2017).

Adhesins: Specific adhesins on the surface of S. Typhi help the bacterium adhere to the intestinal mucosa, facilitating colonization and invasion.

7. Pathogenesis and Disease

Salmonella Typhi is primarily transmitted through the ingestion of contaminated water or food. Once ingested, the bacteria penetrate the intestinal mucosa and are transported to the lymphatic system, where they disseminate to other parts of the body, including the liver, spleen, and bone marrow. Key aspects of its pathogenesis include:

Invasion of Intestinal Epithelium: After ingestion, S. Typhi crosses the gut epithelium through M cells and enters macrophages, where it survives and replicates.

Systemic Spread: The bacteria disseminate from the intestines into the bloodstream, causing bacteremia and systemic symptoms such as fever, abdominal pain, and malaise.

Typhoid Fever: The hallmark of S. Typhi infection is typhoid fever, which presents with prolonged fever, fatigue, headache, abdominal pain, and diarrhea or constipation. If untreated, the infection can progress to severe complications like septicemia, intestinal perforation, and death (Crump et al., 2015).

8. Antibiotic Resistance

Antibiotic resistance in S. Typhi is a growing concern, particularly in areas with endemic typhoid fever. Some strains have developed resistance to first-line antibiotics, including chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Additionally, the emergence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing strains, as well as fluoroquinolone resistance, has complicated treatment options (Chakraborty et al., 2020).

Multidrug-Resistant Strains: MDR S. Typhi strains are resistant to multiple classes of antibiotics, and XDR (extensively drug-resistant) strains have been reported, leading to reliance on third-line antibiotics like azithromycin or ceftriaxone.

9. Prevention and Treatment

Vaccination: Vaccines such as the Ty21a (oral live attenuated vaccine) and the Vi polysaccharide vaccine (injected) are available for the prevention of typhoid fever. However, vaccine coverage and effectiveness can vary, and resistance to vaccination is a concern in endemic regions (Gonzalez et al., 2021).

Antibiotic Treatment: First-line treatment includes antibiotics such as ciprofloxacin or azithromycin, though resistance patterns must be carefully monitored.

Sanitation and Hygiene: Improved sanitation, clean water supply, and proper food handling practices are critical in preventing the spread of typhoid fever.

10. Detection Methods

Culture-based: S. Typhi can be isolated using selective media such as MacConkey agar, SS agar, and XLD agar. It is important to note the non-lactose fermentation and H₂S production as key features.

Serological Tests: Widal test, a serological test that detects antibodies against O and H antigens, is often used to diagnose typhoid fever but has limitations in sensitivity and specificity, particularly in endemic areas (Liu et al., 2017).

Molecular Methods: PCR assays targeting genes like invA, virulence genes, or Vi antigen are becoming more common for rapid detection and identification of S. Typhi.

11. Conclusion

Salmonella enterica subspecies enterica serovar Typhi is a highly pathogenic bacterium responsible for typhoid fever, a systemic illness that remains a major public health concern in many parts of the world. Its distinct cultural and biochemical properties, combined with its virulence factors, make it a formidable pathogen in human populations. Continued efforts in vaccine development, improved sanitation, and antibiotic stewardship are critical to controlling the spread and managing infections caused by S. Typhi.

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References

Bäumler, A. J., & Fang, F. C. (2018). Typhoid fever: Pathogenesis and clinical manifestations. Nature Reviews Microbiology, 16(4), 151-163. https://doi.org/10.1038/s41579-018-0004-4

Crump, J. A., et al. (2015). Typhoid fever and paratyphoid fever in the United States: A systematic review. Journal of Clinical Microbiology, 53(10), 3147-3156. https://doi.org/10.1128/JCM.01710-15

Chakraborty, S., et al. (2020). Antibiotic resistance in Salmonella Typhi isolates from India. Journal of Antimicrobial Chemotherapy, 75(2), 348-354. https://doi.org/10.1093/jac/dkz444

MacLennan, C. A., et al. (2014). The Vi polysaccharide capsule of Salmonella Typhi: A virulence factor and candidate vaccine component. Expert Review of Vaccines, 13(5), 579-591. https://doi.org/10.1586/14760584.2014.913345