Doctoral student discovers new strategy used by listeria bacterium to infect humans and animals

Doctoral student Dongqi Liu, from Purdue University, has made a groundbreaking discovery regarding the foodborne bacterium Listeria monocytogenes. This finding sheds light on a previously unknown invasion strategy that the bacterium employs to infect humans and animals.

Arun Bhunia, a professor of food microbiology at Purdue, emphasized the significance of this discovery, stating that Listeria poses a significant problem in the food industry and for individuals who become infected. In the United States alone, L. monocytogenes infects approximately 1,600 people each year, resulting in around 260 deaths. Pregnant women, unborn fetuses, immunocompromised individuals, and the elderly are particularly susceptible.

Bhunia explained that Listeria contamination can occur in various types of ready-to-eat foods, including fresh produce, fruit, cheese, hot dogs, and sliced meat. Therefore, even commonly enjoyed foods could potentially pose a major health risk. Currently, the only preventive measure is to avoid consuming certain types of food.

When contaminated food is ingested, the bacterium causes listeriosis by traversing the stomach and intestines, subsequently spreading to organs such as the liver, spleen, and even the brain. Bhunia’s previous research demonstrated that the Listeria adhesion protein (LAP) plays a crucial role in facilitating L. monocytogenes’ passage through the intestinal barrier.

However, a lingering question remained regarding LAP: after being secreted by the pathogen, the protein remains on the bacterium’s surface. The mechanism by which it achieves this had remained a mystery, as LAP must remain attached to the bacterial surface for Listeria to cause an infection.

Now, Dongqi Liu, a Bilsland Dissertation Fellow working in Bhunia’s laboratory, has provided an answer to this question. Liu’s research reveals that the bacterium employs a sticky virulence protein known as internalin B to anchor LAP to the bacterial surface.

The details of Liu’s findings, which involved collaboration with 16 researchers from Purdue University and Germany’s Technical University of Braunschweig, were published in the journal Cell Reports.

This newfound understanding of Listeria could potentially lead to more effective preventive measures. Virulence proteins, such as internalin B, are characteristic molecules that are often located in a specific region of the Listeria chromosome known as “the pathogenic island.”

These virulence proteins in the pathogenic island exhibit a unique amino acid sequence tag, which can be used to predict their virulent behavior and mechanisms, including secretion and surface anchoring.

The discovery of LAP’s role in listeriosis might have been delayed due to its location outside the typical chromosomal region associated with virulence factors, and scientists’ limited knowledge of how LAP remains attached to the bacterial surface during infection.

Scientists now understand that internalin B acts as a key player, transforming LAP into a moonlighting pathogenic factor by anchoring it to the host cell’s surface in Listeria. The collaboration between these proteins is crucial for the pathogenesis of the bacterium.

To identify the ligand that binds LAP to cellular surfaces, Liu and his colleagues employed advanced biochemical techniques, including fiber-optic sensors, immunoprecipitation, and mass spectrometry. They described this process as a “ligand fishing” expedition.

LAP is just one component among numerous proteins that Listeria employs to facilitate infection of its host organisms. Unlike traditional virulence factors, LAP functions as a housekeeping enzyme, resulting in distinct virulence regulation and pathogenesis mechanisms.

This alternative strategy of pathogens demonstrates their adaptability in survival and infection, as they can switch to different approaches when necessary. Understanding this strategy offers the potential to prevent future listeriosis outbreaks. Further research may reveal ways to disrupt the bacterium’s ability to remain on the surface or prevent the anchoring of LAP.

Bhunia cautioned that this is a complex process, and finding a single, straightforward solution is unlikely.

The surface secretion and display of proteins, similar to LAP, are also observed in other pathogenic bacteria such as Streptococcus pyogenes and Mycobacterium tuberculosis. LAP is the first protein of its kind to have its surface anchoring mechanism characterized.

During infection, pathogens often secrete large quantities of these enzymes, directly influencing bacterial virulence. Consequently, these proteins or their corresponding antibodies in the host could serve as valuable diagnostic and prognostic markers for infectious diseases.

Bhunia’s interest in studying listeriosis stemmed from numerous serious outbreaks. His team initially identified LAP, and later discovered its role in allowing Listeria to pass through the gut barrier by binding to a receptor on epithelial cells. This alternative intestinal crossing strategy of Listeria was published in 2018 in the journal Cell Host & Microbe.

The newfound understanding of LAP’s anchoring mechanism could assist Bhunia and other researchers in developing antibody supplements or vaccines to prevent listeriosis, particularly in vulnerable populations like pregnant women. Bhunia has patented a bioengineered probiotic that shows promise in preventing infections. Occasionally, women who have experienced listeriosis-related pregnancy complications reach out to Bhunia for assistance.

Bhunia emphasized the personal connection and motivation behind his work, always keeping in mind the people he aims to help when studying Listeria.

Source: Purdue University

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