The sRNA DicF integrates oxygen sensing to enhance enterohemorrhagic<i>Escherichia coli</i>virulence via distinctive RNA control mechanisms

Melson, Elizabeth M.; Kendall, Melissa M.

doi:10.1073/pnas.1902725116

Cited by 42 publications

(50 citation statements)

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“…The authors of this study suggest that stability of DicF is differentially regulated such that it is more stable under anaerobic growth conditions and degraded faster under aerobic conditions. A very recent study found that four DicF orthologs encoded by different prophages in E. coli O157:H7 are produced under microaerobic growth conditions (31). These DicF sRNAs promote low oxygen-responsive virulence gene expression via base pairing-mediated regulation of a key virulence transcription factor.…”

Section: Discussionmentioning

confidence: 99%

“…DicA represses the dicBF operon promoter (which is similar to the λ phage P L promoter) and the natural condition(s) leading to induction of the operon are unknown (29). DicB and DicF are conserved in many strains of E. coli , and interestingly, many strains of pathogenic E. coli possess multiple cryptic prophages encoding dicBF operons (25, 30, 31).…”

Section: Introductionmentioning

confidence: 99%

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Cryptic prophage-encoded small protein DicB protectsEscherichia colifrom phage infection by inhibiting inner membrane receptor proteins

Ragunathan

Vanderpool

2019

Preprint

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14Bacterial genomes harbor cryptic prophages that have lost genes required for induction, 15 excision from host chromosomes, or production of phage progeny. Escherichia coli K12 strains 16 contain a cryptic prophage Qin that encodes a small RNA, DicF, and small protein, DicB, that 17 have been implicated in control of bacterial metabolism and cell division. Since DicB and DicF 18 are encoded in the Qin immunity region, we tested whether these gene products could protect 19 the E. coli host from bacteriophage infection. Transient expression of the dicBF operon yielded 20 cells that were ~100-fold more resistant to infection by λ phage than control cells, and the 21 phenotype was DicB-dependent. DicB specifically inhibited infection by λ and other phages that 22 use ManYZ membrane proteins for cytoplasmic entry of phage DNA. In addition to blocking 23ManYZ-dependent phage infection, DicB also inhibited the canonical sugar transport activity of 24ManYZ. Previous studies demonstrated that DicB interacts with MinC, an FtsZ polymerization 25 inhibitor, causing MinC localization to mid-cell and preventing Z ring formation and cell division. 26In strains producing mutant MinC proteins that do not interact with DicB, both DicB-dependent 27 phenotypes involving ManYZ were lost. These results suggest that DicB is a pleiotropic 28 regulator of bacterial physiology and cell division, and that these effects are mediated by a key 29 molecular interaction with the cell division protein MinC. 30 31 32 33 Importance 34Temperate bacteriophages can integrate their genomes into the bacterial host chromosome and 35 exist as prophages whose gene products play key roles in bacterial fitness and interactions with 36 eukaryotic host organisms. Most bacterial chromosomes contain "cryptic" prophages that have 37 lost genes required for production of phage progeny but retain genes of unknown function that 38 may be important for regulating bacterial host physiology. This study provides such an example 39 -where a cryptic prophage-encoded product can perform multiple roles in the bacterial host and 40 influence processes including metabolism, cell division, and susceptibility to phage infection. 41 Further functional characterization of cryptic prophage-encoded functions will shed new light on 42 host-phage interactions and their cellular physiological implications. 43 44 (prophage) is called a lysogen. Changes in host metabolic conditions or external environmental 55 triggers can induce the prophage, which then excises out of the host chromosome and resumes 56 a lytic lifecycle (4, 5). 57 Nearly half of all sequenced bacterial genomes have been found to contain at least one 58 prophage, with many genomes containing multiple prophages (6). Lysogeny comes at a cost to 59 the bacterial host due to the extra burden of replication of prophage DNA and the threat of 60 lysogen induction which is lethal to the host cell. On the other hand, there are many well-61 documented examples of lysogenic conversion, where prophage-encoded products confer ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cryptic prophage-encoded small protein DicB protectsEscherichia colifrom phage infection by inhibiting inner membrane receptor proteins

Ragunathan

Vanderpool

2019

Preprint

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“…When enterohemorrhagic Escherichia coli O157:H7 (EHEC), a food-borne pathogen, enters the digestive tract, it must adapt from oxygen rich environments to an increasingly oxygenlimiting environment toward the colon, where pathogens sense the differential gas concentrations and start to express their virulence factors (Melson and Kendall, 2019). As mentioned above, this is a key behavior of bacterial strains in order to set the basis of the infection onset, which seems to have evolved to start from a very low number of input cells (Van Elsas et al, 2011).…”

Section: Gastrointestinal Pathogenic Diseasesmentioning

confidence: 99%

“…As mentioned above, this is a key behavior of bacterial strains in order to set the basis of the infection onset, which seems to have evolved to start from a very low number of input cells (Van Elsas et al, 2011). DicF is a sRNA dependent on Hfq directly targeting the SD sequence of the transcriptional activator pchA, to promote its expression under low oxygen conditions (Melson and Kendall, 2019; Table 2). Ultimately, DicF has an effect over virulence by indirect increase of the expression of the locus of enterocyte effacement (LEE) pathogenicity island, but only when Hfq is present and oxygen concentration is very low (Figure 8).…”

Section: Gastrointestinal Pathogenic Diseasesmentioning

confidence: 99%

Small RNAs as Fundamental Players in the Transference of Information During Bacterial Infectious Diseases

Plaza

2020

Front. Mol. Biosci.

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Communication shapes life on Earth. Transference of information has played a paramount role on the evolution of all living or extinct organisms since the appearance of life. Success or failure in this process will determine the prevalence or disappearance of a certain set of genes, the basis of Darwinian paradigm. Among different molecules used for transmission or reception of information, RNA plays a key role. For instance, the early precursors of life were information molecules based in primitive RNA forms. A growing field of research has focused on the contribution of small non-coding RNA forms due to its role on infectious diseases. These are short RNA species that carry out regulatory tasks in cis or trans. Small RNAs have shown their relevance in fine tuning the expression and activity of important regulators of essential genes for bacteria. Regulation of targets occurs through a plethora of mechanisms, including mRNA stabilization/destabilization, driving target mRNAs to degradation, or direct binding to regulatory proteins. Different studies have been conducted during the interplay of pathogenic bacteria with several hosts, including humans, animals, or plants. The sRNAs help the invader to quickly adapt to the change in environmental conditions when it enters in the host, or passes to a free state. The adaptation is achieved by direct targeting of the pathogen genes, or subversion of the host immune system. Pathogens trigger also an immune response in the host, which has been shown as well to be regulated by a wide range of sRNAs. This review focuses on the most recent host-pathogen interaction studies during bacterial infectious diseases, providing the perspective of the pathogen.

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“…RNA purity was determined by measuring the A 260 /A 280 ratio and by performing PCR (35 cycles). qPCR was performed in a one-step reaction using an ABI 7500-FAST sequence detection system and software (Applied Biosystems) essentially as described previously (45). For each 10-l reaction mixture, 5 l of 2ϫ SYBR master mix (Ambion), 0.05 l of Multi-Scribe reverse transcriptase (Invitrogen), and 0.05 l of RNase inhibitor (Invitrogen) were added.…”

Section: Figmentioning

confidence: 99%

Effect of Lipidation on the Localization and Activity of a Lysozyme Inhibitor in Neisseria gonorrhoeae

et al. 2020

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The Gram-negative pathogen Neisseria gonorrhoeae (gonococcus [Gc]) colonizes lysozyme-rich mucosal surfaces. Lysozyme hydrolyzes peptidoglycan, leading to bacterial lysis. Gc expresses two proteins, SliC and NgACP, that bind and inhibit the enzymatic activity of lysozyme. SliC is a surface-exposed lipoprotein, while NgACP is found in the periplasm and also released extracellularly. Purified SliC and NgACP similarly inhibit lysozyme. However, whereas mutation of ngACP increases Gc susceptibility to lysozyme, the sliC mutant is only susceptible to lysozyme when ngACP is inactivated. In this work, we examined how lipidation contributes to SliC expression, cellular localization, and resistance of Gc to killing by lysozyme. To do so, we mutated the conserved cysteine residue (C18) in the N-terminal lipobox motif of SliC, the site for lipid anchor attachment, to alanine. SliC(C18A) localized to soluble rather than membrane fractions in Gc and was not displayed on the bacterial surface. Less SliC(C18A) was detected in Gc lysates compared to the wild-type protein. This was due in part to some release of the C18A mutant, but not wild-type, protein into the extracellular space. Surprisingly, Gc expressing SliC(C18A) survived better than SliC (wild type)-expressing Gc after exposure to lysozyme. We conclude that lipidation is not required for the ability of SliC to inhibit lysozyme, even though the lipidated cysteine is 100% conserved in Gc SliC alleles. These findings shed light on how members of the growing family of lysozyme inhibitors with distinct subcellular localizations contribute to bacterial defense against lysozyme. IMPORTANCE Neisseria gonorrhoeae is one of many bacterial species that express multiple lysozyme inhibitors. It is unclear how inhibitors that differ in their subcellular localization contribute to defense from lysozyme. We investigated how lipidation of SliC, an MliC (membrane-bound lysozyme inhibitor of c-type lysozyme)-type inhibitor, contributes to its localization and lysozyme inhibitory activity. We found that lipidation was required for surface exposure of SliC and yet was dispensable for protecting the gonococcus from killing by lysozyme. To our knowledge, this is the first time the role of lipid anchoring of a lysozyme inhibitor has been investigated. These results help us understand how different lysozyme inhibitors are localized in bacteria and how this impacts resistance to lysozyme.

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The sRNA DicF integrates oxygen sensing to enhance enterohemorrhagicEscherichia colivirulence via distinctive RNA control mechanisms

Cited by 42 publications

References 59 publications

Cryptic prophage-encoded small protein DicB protectsEscherichia colifrom phage infection by inhibiting inner membrane receptor proteins

Cryptic prophage-encoded small protein DicB protectsEscherichia colifrom phage infection by inhibiting inner membrane receptor proteins

Small RNAs as Fundamental Players in the Transference of Information During Bacterial Infectious Diseases

Effect of Lipidation on the Localization and Activity of a Lysozyme Inhibitor in Neisseria gonorrhoeae

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