Tag Archives: Cytoplasm

Study highlights two strategies used by Salmonella to escape the human body’s defenses

Like thieves that constantly look for ways to evade capture, Salmonella enterica, a disease-causing bacterium, uses various tactics to escape the human body’s defense mechanisms. In a new study, researchers from the Department of Microbiology and Cell Biology (MCB), IISc, highlight two such strategies that the bacterium uses to protect itself, both driven by the same protein.

When Salmonella enters the human body, each bacterial cell resides within a bubble-like structure known as Salmonella-containing vacuole (SCV). In response to the bacterial infection, the immune cells in our body produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with pathways triggered to break down these SCVs and fuse them with cellular bodies called lysosomes or autophagosomes, which destroy the bacteria. However, these bacteria have developed robust mechanisms to maintain vacuolar integrity, which is crucial for their survival. For example, when a bacterial cell divides, the vacuole surrounding it also divides, enabling every new bacterial cell to be ensconced in a vacuole. This also ensures that more vacuoles are present than the number of lysosomes which can digest them.

In the study published in Microbes and Infection, the IISc team deduced that a critical protein produced by Salmonella, known as SopB, prevents both the fusion of SCV with lysosomes as well as the production of lysosomes, in a two-pronged approach to protect the bacterium. “[This] gives the upper hand to bacteria to survive inside macrophages or other host cells,” explains Ritika Chatterjee, former PhD student in MCB and first author of the study. The experiments were carried out on immune cell lines and immune cells extracted from mice models.

SopB acts as a phosphatase – it aids in removing phosphate groups from phosphoinositide, a type of membrane lipid. SopB helps Salmonella change the dynamics of the vacuole – specifically it alters the type of inositol phosphates in the vacuole membrane – which prevents the vacuole’s fusion with lysosomes.

A previous study from the same team had reported that the number of lysosomes produced by the host cells decreases upon infection with Salmonella. The researchers also found that mutant bacteria that were unable to produce SopB were also unable to reduce host lysosome numbers. Therefore, they decided to look more closely at the role that SopB was playing in the production of lysosomes, using advanced imaging techniques.

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What they found was that SopB prevents the translocation of a critical molecule called Transcription Factor EB (TFEB) from the cytoplasm of the host cell into the nucleus. This translocation is vital because TFEB acts as a master regulator of lysosome production.

This is the first time we deciphered that SopB can work in a dual manner – it changes the phosphoinositide dynamics of SCV and affects TFEB’s translocation into the nucleus. While other groups have already reported the function of SopB in mediating invasion in epithelial cells, the novelty of our study lies in identification of the function of SopB in inhibiting the vacuolar fusion with existing autophagosomes/lysosomes, and the second mechanism, which provides Salmonella with a survival advantage by increasing the ratio of SCV to lysosomes.”

Dipshikha Chakravortty, Professor at MCB and corresponding author of the study

The researchers suggest that using small molecule inhibitors against SopB or activators of TFEB can help counter Salmonella infection.

In subsequent studies, the team plans to explore the role of another host protein called Syntaxin-17 whose levels also reduce during Salmonella infection. “How do the SCVs reduce the levels of Syntaxin-17? Do they exchange it with some other molecules, or do the bacteria degrade it? We [plan to] look into it next,” says Chakravortty.

Journal reference:

Chatterjee, R., et al. (2023) Deceiving The Big Eaters: Salmonella Typhimurium SopB subverts host cell Xenophagy in macrophages via dual mechanisms. Microbes and Infection. doi.org/10.1016/j.micinf.2023.105128.

Enveloped viruses show greater cross-species transmission, according to new research

A study published in PNAS Microbiology found that enveloped viruses harbor greater cross-species transmissibility and are more likely to cause zoonotic infections than nonenveloped viruses. The research suggested that viral envelopes aid these pathogens in evading host immunity.

Study: Enveloped viruses show increased propensity to cross-species transmission and zoonosis. Image Credit: Kateryna Kon/Shutterstock
Study: Enveloped viruses show increased propensity to cross-species transmission and zoonosis. Image Credit: Kateryna Kon/Shutterstock


Zoonosis refers to the spread of infectious diseases between animals and humans (or between humans and animals). In the past few decades, the cross-species transmission of viruses from wild or domestic animals to humans (zoonoses) has led to major epidemics. Still, our understanding of this complex process remains limited.

Several well-known zoonoses include human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), Zika, Ebola, influenza, COVID, and mpox. Therefore, understanding and predicting virus emergence has become a scientific priority. Several zoonotic risk factors exist, including biodiversity elimination and species invasions, viral host variability, interaction frequency, life cycle characteristics of reservoir hosts, wildlife trade, and host closeness to humans.

Nevertheless, prior studies have revealed that three factors have been identified as contributing to the risk of zoonotic disease spread – viral genetic material – ribonucleic acid (RNA) viruses may be more susceptible than DNA viruses; replication site – viruses that replicate in the host cytoplasm rather than the nucleus may have an advantage; and genome size – smaller genomes may be more zoonotic.

The enveloped nature of viruses is a characteristic feature that distinguishes them from other organisms. Most zoonotic viruses that have caused human disease in the past were enveloped, such as – smallpox, mpox, coronaviruses, rabies, measles, and influenza.

A virus’s genome can provide information regarding host tropism and zoonotic propensity by evaluating characteristics like codon or dinucleotide usage biases and the degree to which these biases reflect those observed in the host-gene transcripts. The fundamental features of viruses remain unknown despite these advancements in understanding cross-species transmission and zoonosis.

The study

Using a database of over 12,000 mammalian virus–host interactions, the current work explored key virological properties that influence cross-species transmissibility and zoonotic propensity to understand better which viral characteristics predominantly determine zoonosis.

Here, the researchers examined a large VIRION database containing 5,149 viruses identified through metagenomic studies. This exploratory analysis utilized the Global Virome in One Network (VIRION) database. Overall, 5,149 viruses belonging to 36 families and 1,599 host species were analyzed from 20 orders, revealing 12,888 virus-host associations. 

Following this, the fundamental characteristics of the viruses were defined based on –their genetic material; single or double-stranded; segmented or non-segmented, replicating in the cytoplasm or nucleus, enveloped or nonenveloped, and the genome size. 

For each virus, the number of natural host species was identified and recorded, excluding humans, to reduce the possibility of bias. The mammalian viruses were then examined for their potential pathogenicity, i.e., their ability for zoonosis.

The findings

The results showed that the number of host species increased more rapidly for enveloped viruses than for non-enveloped viruses, being approximately twice as high for the former type. This difference was also discernible when the envelope factor was combined with the other viral characteristics. 

All other viral characteristics examined were either not significant or marginally significant. Enveloped viruses were more likely to undergo cross-species transmission than nonenveloped viruses. 

It was noted that enveloped viruses tend to have a higher proportion of zoonotic spread than non-enveloped viruses. Using binary logistic regression with N ≥5 sequence records, zoonotic propensity was estimated to increase 2.5-fold for enveloped viruses compared to non-enveloped viruses. Thus, enveloped viruses showed a higher propensity for zoonotic spillover than non-enveloped viruses.

Meanwhile, viruses replicating in the cytoplasm were found to be more likely (1.9 times) to be zoonotic than those replicating in the nucleus. Segmented viruses heightened the chances for zoonosis slightly more than non-segmented viruses. Further, viruses with smaller genomes had a greater probability of precipitating zoonotic infection. 

The lack of significant effects of these two features on cross-species transmission meant that their impact on zoonotic propensity could either be due to human-specific factors or, more likely, to biases within the human-infectious virus datasets.

This study also provided insights into how enveloped viruses might infect hosts. It was likely that envelope proteins were structurally less constraining than capsid proteins, allowing enveloped viruses to bind cellular receptors from different host species with greater flexibility, bind to a larger number of alternative receptors, or accommodate host-switch mutations without compromising other functions. 

Another possible mechanism is an apoptotic mimicry, in which viral particles are engulfed by host cells disguised as apoptotic bodies with defined membrane lipid conformations and get introduced into the host cells. 


The results revealed that enveloped viruses infect more host species and are more likely to be zoonotic than non-enveloped viruses. In contrast, other viral characteristics, such as genome composition, structure, size, and the viral replication compartment, are less significant. 

According to this study, viral envelopes did not significantly impact or even reduce the zoonotic risk contrary to the prior belief, and this may help in prioritizing outbreak prevention efforts. A viral envelope may facilitate cross-species transmission by facilitating structural flexibility of the receptor-binding proteins and allowing for overcoming the viral entry barriers.

Journal reference: