Random Selection Of Micro-organisms ; 4) Leptospira interrogans - a spirochetes

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So we are here by taking our tour furhter on our 4th Oraganism in Series of Random Selection of Micro-organism by Concept Of Microbiology 
We all heard about spirochete but today we are finally going to a detailed one exploration tour with Concept Of Microbiology 
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Leptospira interrogans :

Leptospira interrogans is a Gram negative, obligate aerobe spirochete, with periplasmic flagella. When viewed through a dark-field microscope, it often resembles a question mark, and this gives the species its name. It is a member of the genus Leptospira. Some important pathogenic serovars from this species are Canicola, Icterohaemorrhagiae and Australis. L. interrogans is difficult to culture, requiring special media and extended incubation periods.


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 interrogans

Introduction :

Leptospira interrogans is a Gram negative, obligate aerobe spirochete, with periplasmic flagella. When viewed through a dark-field microscope, it often resembles a question mark, and this gives the species its name. 
It is a member of the genus Leptospira. Some important pathogenic serovars from this species are Canicola, Icterohaemorrhagiae and Australis. 
L. interrogans is difficult to culture, requiring special media and extended incubation periods.

L. interrogans infects wild and domestic animals, including pet dogs. Humans are accidental hosts. It can survive in neutral or slightly alkaline water for 3 months or longer.

L. interrogans is usually transmitted to humans through contact with infected animal urine, either directly or in water. 

It invades directly through broken skin and can replicate in the liver and kidneys. Risk factors for infection include working in sewers, farming, and recreational water activities. 

Infection is known as leptospirosis, which can be asymptomatic, a mild non-specific illness, or result in death from liver damage and kidney failure (Weil's syndrome)

Ecology : 

Leptospira interrogans is a bacterial zoonosis with a worldwide distribution for which rats (Rattus spp.) are the primary reservoir in urban settings. 
In order to assess, monitor, and mitigate the risk to humans, it is important to understand the ecology of this pathogen in rats.
 The objective of this study was to characterize the ecology of L. interrogans in Norway rats (Rattus norvegicus) in an impoverished inner-city neighborhood of Vancouver, Canada.

Cell Structure : 

Leptospira interrogans is a type of gram negative bacteria.
The cell is thin and spiral shaped with a hook on each end.
It is motile and possesses two periplasmic flagella
✓Serovars
The L. interrogans species can be broken down into roughly 290 serovars.

Leptospiral serovar diversity results from structural differences in carbohydrate component of lipopolysaccharides 
Many serovars are adapted for specific mammalian reservoir hosts.

Many serovars have structural differences, but their genomes and mechanisms of infection remain extremely similar

Metabolisms :

Metabolism Leptospira interrogans is an aerobic bacteria and possesses both catalase and oxidase enzymes and does not ferment carbohydrates.Leptospira species have only one glucose uptake system. 

This system is a glucose-sodium symporter that is dependent on a sodium gradient across the bacterial membrane 
This limited system results in an inability to utilize glucose as an energy source in many environments.

Consequently, Leptospira species utilize beta-oxidation of long-chain fatty acids as the major energy and carbon source instead of the more common sugar oxidative pathways.

Pathogenesis : 

Infection by pathogenic strains of Leptospira commonly occurs through direct contact with infected animal urine or indirectly through contaminated water. Almost every mammal can serve as a carrier of leptospires, harboring the spirochete in the proximal renal tubules of the kidneys, leading to urinary shedding


Infection
L. interrogans can be spread through the bodily fluids, excluding the saliva, of infected animals. The bacteria can enter the body through skin or mucous membranes and via consumption of contaminated water.


 Infected wild and domestic animals may continue to excrete the bacteria into the environment for up to several years and the bacteria can remain in soil and water for months at a time.

 The ability of the pathogen to remain viable in soil and water supplies makes it extremely dangerous and prevalent in developing nations where food and water sources are not always sanitized prior to consumption. 

Once the bacteria has been ingested, virulence mechanisms such as motility and chemotaxis responses that are extensively coded for the in the genome enable bacteria to penetrate the host tissues rapidly.

 Motility contributes greatly to the decimating effect of the disease from the site of entry to sites of end-organ damage in the lungs, liver, kidney, eyes, and brain.


 The flagella and shape of the cells allow them to move through the body and the hooks on the ends of their cells allow them to attach and latch on to host tissues.


 After reaching the blood stream, targeted sites of colonization are the liver and kidneys. These organs have a large supply of lipids that are essential for the growth and survival of L. interrogans. 


L. interrogans tends to bind  a variety of cell lines including fibroblasts, endothelial cells, and kidney epithelial cells.

 Once the bacteria attach to the host cell, L. interrogans cells secrete enzymes that degrade host cell matrices, allowing for faster invasion and infection. 

The bacteria reproduce within the cell and are released slowly into the surrounding environmnt while waiting for the immune system to mount a response.

 Virulent leptospiras can protect themselves against phagocytic cells and the complement system. Pathogenic leptospiras escape from phagocytosis, are resistant to intracellular killing mechanisms and evade the complement system by binding to complement system inhibitor FH.


 FH is a regulatory complement protein that prevents complement activation and binding to it can restrict the deposition of the late complement components on bacteria surfaces.


 Once the host immune system does kill the bacteria, the bacteria release endotoxins. The innate immune system recognizes endotoxins through specific receptors and mediates a response by Toll-like receptors and Na+/K+-ATPase . 

These sense antigen molecules and trigger intracellular signaling pathways driving the translocation of transcription factors which lead to increased inflammatory mediator production, creating an inflammatory microenvironment that can lead to organ dysfunction.


 After infection, acquired immunity does sometimes occur, but it seems to be dependent on the specific serovar of infection.

 Patients who have recovered from leptospirosis do not seem to generate memory T cells that can be activated by in vitro stimulation with Leptospiral protein antigens.

Antibiotic Resistance : 

Leptospira interrogans is a bacterial zoonosis with a worldwide distribution for which rats (Rattus spp.) are the primary reservoir in urban settings. 
In order to assess, monitor, and mitigate the risk to humans, it is important to understand the ecology of this pathogen in rats.
contrast to the findings discussed above, the Leptospira strains tested were found to be highly resistant to amphotericin B, 
5-fluorouracil, 
fosfomycin, 
sulfamethoxazole, and trimethoprim 

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