Pathogenic Salmonella bacteria.
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The authors, a research team led by Cari Vanderpool and Sabrina Abdulla of the Carl R. Woese Institute for Genomic Biology (IGB) and the Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA, have shown how the virulence of the pathogenic bacteria, Salmonella, is controlled.
The bad news for Creationists is that:
- It shows that if this system was designed by an intelligent entity, that entity intended to make people sick, because that's what it does.
- It involved control of a system known as the type III secretory system, which is related to and very similar to the Type II secretory system that biologists believe was the evolutionary ancestor of the bacterial flagella that Creationist dogma insists was intelligently designed because it couldn't have evolved.
Infections with Salmonella species represent a significant public health problem due to their large and varied animal reservoir, presence of human and animal carrier states, and the lack of coordinated programs for control. Although cases of human salmonellosis have been steadily declining since 1995, it remains one of the most important human food-borne diseases. Salmonella has evolved to live in the gastrointestinal tracts of animals. Thus the primary sources of contamination are animals and their feces. In recent years, the significance of foods of vegetable origin as likely vehicles of gastrointestinal infection has been highlighted.Regrettably, the published paper in the Journal of Bacteriology is behind a paywall. However, the IGB news release explains the work and its significance:
Salmonella are food-borne pathogens that infect millions of people a year. To do so, these bacteria depend on a complex network of genes and gene products that allow them to sense environmental conditions. In a new paper, researchers have investigated the role of small RNAs that help Salmonella express their virulence genes.Technical details are given in the teams published paper:
The bacteria infect humans by first invading the cells of the intestine using a needle-like structure, called a type 3 secretion system. This structure injects proteins directly into the cells, setting off a cascade of changes that cause inflammation, and ultimately cause diarrhea. The genes that encode this system, and other genes that are needed for invasion, are found on a region of DNA known as the Salmonella pathogenicity island 1 [SPI-1].
SPI-1 is controlled by an extensive regulatory network. First, three transcription factors: HilD, HilC, and RtsA, all control their own and each other’s DNA expression. They also activate another transcription factor, HilA, which activates the rest of the SPI-1 genes. If this isn’t complicated enough, SPI-1 also needs to sense a variety of environmental cues and tune the expression of its genes in order to infect its host.SPI-1 needs to be well controlled. If the type 3 secretion system needle apparatus is not made, Salmonella cannot cause an infection, and if too much of the needle apparatus is made, it makes Salmonella sick.
We have known for a long time that there are a lot of environmental factors that feed into the gene regulation in Salmonella. However, we didn’t know how. That’s when researchers started looking at small RNAs
The starting point for my work was the observation that when we deleted the 3’ UTR, the expression of the hilD gene went up 60-fold,” Abdulla said. “We then decided to look for sRNAs that might be interacting with this region.
This result suggests that the entire 3’ UTR is important for regulation. We showed that the sRNAs stabilize the hilD mRNA and protect it from being degraded.
Such long 3’ UTRs have not been well studied. With more genomic research, people are realizing more and more that these longer regions exist and that they are important for regulation.
We found that when the sRNAs are deleted, the bacteria cannot survive in the host. We also showed that the sRNAs play a role in helping SPI-1 invade the host cells.
Sabrina Abdulla, first author
Department of Microbiology
University of Illinois at Urbana-Champaign
Urbana, Illinois, USA
Small RNAs play a crucial role in determining how genes function in bacterial cells. Typically, these molecules either interact with proteins, or the mRNA, which carries the instructions for making proteins. As a result, sRNAs affect a variety of bacterial functions, including virulence and responses to the environment.
In this paper, the researchers looked at the sRNAs that regulate the hilD mRNA, specifically a sequence on the mRNA called the 3’ untranslated region, a part of the mRNA not involved in making the HilD protein. In bacteria, the 3’ UTRs are usually 50-100 nucleotides long. However, the 3’ UTR of the hilD mRNA was 300 nucleotides long.Now that we know that sRNAs play an important role in controlling SPI-1 through their regulatory effects on the hilD 3’ UTR, we want to extend our studies in two directions. We’d like to understand more about how, at a molecular level, the sRNAs influence hilD mRNA levels. We’d also like to better understand how sRNAs participate in regulating expression of other important SPI-1 genes.
Professor Cari Vanderpool (MME/IGOH), Senior author
Professor of microbiology.
Department of Microbiology
University of Illinois at Urbana-Champaign
Urbana, Illinois, USA
The researchers determined that although the sRNAs Spot 42 and SdsR can both target the 3’ UTR, they do so in different regions.
Using mice, the researchers also looked at whether Spot 42 and SdsR can affect how Salmonella causes infections. They performed mouse competition assays, where they introduced mutant bacteria that lacked the sRNAs and bacteria that contained the sRNAs, to see which strains survive and cause infection.
ABSTRACTClearly, a Creationist is obliged to believe that their putative intelligent [sic] designer went to great lengths to come up with this complex system to control the mechanism it designed to make us sick - the type III secretory system. It then appears to have reinvented most of the components of this system to create the bacterial flagellum, if you believe Creationist claims. And of course, to a Creationist, that's a much more sensible explanation than that this system evolved by a natural, mindless, utilitarian process with no plan and no motive, and that the components of that system were then repurposed by evolution to give bacteria a propulsion system.
Salmonella enterica serovar Typhimurium is an enteric pathogen associated with foodborne disease. Salmonella invades the intestinal epithelium using a type three secretion system encoded on Salmonella pathogenicity island 1 (SPI-1). SPI-1 genes are tightly regulated by a complex feed-forward loop to ensure proper spatial and temporal expression. Most regulatory input is integrated at HilD, through control of hilD mRNA translation or HilD protein activity. The hilD mRNA possesses a 310-nucleotide 3′ untranslated region (UTR) that influences HilD and SPI-1 expression, and this regulation is dependent on Hfq and RNase E, cofactors known to mediate small RNA (sRNA) activities. Thus, we hypothesized that the hilD mRNA 3′ UTR is a target for sRNAs. Here, we show that two sRNAs, SdsR and Spot 42, regulate SPI-1 by targeting different regions of the hilD mRNA 3′ UTR. Regulatory activities of these sRNAs depended on Hfq and RNase E, in agreement with previous roles found for both at the hilD 3′ UTR. Salmonella mutants lacking SdsR and Spot 42 had decreased virulence in a mouse model of infection. Collectively, this work suggests that these sRNAs targeting the hilD mRNA 3′ UTR increase hilD mRNA levels by interfering with RNase E-dependent mRNA degradation and that this regulatory effect is required for Salmonella invasiveness. Our work provides novel insights into mechanisms of sRNA regulation at bacterial mRNA 3′ UTRs and adds to our knowledge of post-transcriptional regulation of the SPI-1 complex feed-forward loop.
IMPORTANCE Salmonella enterica serovar Typhimurium is a prominent foodborne pathogen, infecting millions of people a year. To express virulence genes at the correct time and place in the host, Salmonella uses a complex regulatory network that senses environmental conditions. Known for their role in allowing quick responses to stress and virulence conditions, we investigated the role of small RNAs in facilitating precise expression of virulence genes. We found that the 3′ untranslated region of the hilD mRNA, encoding a key virulence regulator, is a target for small RNAs and RNase E. The small RNAs stabilize hilD mRNA to allow proper expression of Salmonella virulence genes in the host.
Abdulla, Sabrina Z.; Kim, Kyungsub; Azam, Muhammad S.; Golubeva, Yekaterina A.; Cakar, Fatih; Slauch, James M.; Vanderpool, Carin K.
Small RNAs Activate Salmonella Pathogenicity Island 1 by Modulating mRNA Stability through the hilD mRNA 3′ Untranslated Region
Journal of Bacteriology; e00333-22. DOI: 10.1128/jb.00333-22
© 2022 American Society for Microbiology.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.
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