Regulation of Gene Expression in Response to Environmental Changes in Bacterial Pathogens

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 21973

Special Issue Editors


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Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, Via Selmi 3 - room 98, 40126 Bologna, Italy
Interests: bacterial pathogens; virulence genes regulation; comparative transcriptomics; ChIP-sequencing; regulatory DNA-binding proteins; regulatory small-RNAs; transcriptional regulation; Helicobacter pylori; Neisseria meningitidis; heat–shock response; environmental regulation

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Co-Guest Editor
Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy
Interests: human pathogens; virulence factors; comparative transcriptomics; ChIP-sequencing
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Special Issue Information

Dear Colleagues,

The ability of bacteria to gauge surroundings and modulate gene expression accordingly represents a crucial feature for their survival. In this respect, bacteria have evolved several transcriptional and posttranscriptional strategies that can act all along the gene expression process. The regulation of gene transcription is a fundamental process in all living organisms, where DNA-binding transcriptional regulators play a crucial role. Bacteria typically enroll an arsenal of transcriptional regulators to orchestrate gene transcription in response to external stimuli. Once an environmental signal is perceived, it is transduced to invoke specific molecular mechanisms controlling transcription of genes coding for proteins capable of assisting the adaptation to the new condition. Transcriptional responses can be under either positive or negative control mediated by dedicated regulatory proteins. Positive regulation exploits specific alternative sigma factors to redirect the RNA polymerase enzyme to a subset of selected promoters, transcriptional activators, or their combination, while negative regulation is mediated by transcriptional repressors. Interestingly, in some microorganisms these two opposite strategies coexist, establishing complex regulatory networks. In addition to regulatory proteins, small RNAs (sRNAs) are widely adopted by bacteria in response to changes in the environment. Accumulating studies on bacterial regulatory processes clearly established that sRNAs modulate their target gene expression generally at the post-transcriptional level. Understanding the complexity of such networks requires a combination of interdisciplinary approaches such as molecular biology, biochemistry, and biophysics together with novel high-throughput genomics techniques, bioinformatics, and computational analyses.

This Special Issue of Microorganisms will be dedicated to pooling together aspects of the aforementioned topics, providing forefront studies and perspectives in the field of bacterial pathogens networks biology.

Prof. Dr. Vincenzo Scarlato
Prof. Dr. Davide Roncarati
Guest Editors

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Keywords

  • Bacterial pathogens
  • gene expression
  • two-component system
  • activator of transcription, repressors of transcription, sigma factor
  • genome-wide approaches
  • chip-sequencing
  • RNA-sequencing
  • regulatory sRNA
  • metal homeostasis
  • virulence factors regulation

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Published Papers (6 papers)

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Research

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16 pages, 2252 KiB  
Article
Multilayer Regulation of Neisseria meningitidis NHBA at Physiologically Relevant Temperatures
by Sara Borghi, Ana Antunes, Andreas F. Haag, Marco Spinsanti, Tarcisio Brignoli, Enea Ndoni, Vincenzo Scarlato and Isabel Delany
Microorganisms 2022, 10(4), 834; https://doi.org/10.3390/microorganisms10040834 - 18 Apr 2022
Cited by 2 | Viewed by 2556
Abstract
Neisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms. Diverse roles have been reported for NHBA in [...] Read more.
Neisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms. Diverse roles have been reported for NHBA in heparin-mediated serum resistance, biofilm formation, and adherence to host tissues. We determined that temperature controls the expression of NHBA in all strains tested, with increased levels at 30–32 °C compared to 37 °C. Higher NHBA expression at lower temperatures was measurable both at mRNA and protein levels, resulting in higher surface exposure. Detailed molecular analysis indicated that multiple molecular mechanisms are responsible for the thermoregulated NHBA expression. The comparison of mRNA steady-state levels and half-lives at 30 °C and 37 °C demonstrated an increased mRNA stability/translatability at lower temperatures. Protein stability was also impacted, resulting in higher NHBA stability at lower temperatures. Ultimately, increased NHBA expression resulted in higher susceptibility to complement-mediated killing. We propose that NHBA regulation in response to temperature downshift might be physiologically relevant during transmission and the initial step(s) of interaction within the host nasopharynx. Together these data describe the importance of NHBA both as a virulence factor and as a vaccine antigen during neisserial colonization and invasion. Full article
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15 pages, 2215 KiB  
Article
Effect of a Defective Clamp Loader Complex of DNA Polymerase III on Growth and SOS Response in Pseudomonas aeruginosa
by Maria Concetta Spinnato, Alessandra Lo Sciuto, Jessica Mercolino, Massimiliano Lucidi, Livia Leoni, Giordano Rampioni, Paolo Visca and Francesco Imperi
Microorganisms 2022, 10(2), 423; https://doi.org/10.3390/microorganisms10020423 - 12 Feb 2022
Cited by 3 | Viewed by 2911
Abstract
DNA polymerase III (Pol III) is the replicative enzyme in bacteria. It consists of three subcomplexes, the catalytic core, the β clamp, and the clamp loader. While this complex has been thoroughly characterized in the model organism Escherichia coli, much less is [...] Read more.
DNA polymerase III (Pol III) is the replicative enzyme in bacteria. It consists of three subcomplexes, the catalytic core, the β clamp, and the clamp loader. While this complex has been thoroughly characterized in the model organism Escherichia coli, much less is known about its functioning and/or its specific properties in other bacteria. Biochemical studies highlighted specific features in the clamp loader subunit ψ of Pseudomonas aeruginosa as compared to its E. coli counterpart, and transposon mutagenesis projects identified the ψ-encoding gene holD among the strictly essential core genes of P. aeruginosa. By generating a P. aeruginosa holD conditional mutant, here we demonstrate that, as previously observed for E. coli holD mutants, HolD-depleted P. aeruginosa cells show strongly decreased growth, induction of the SOS response, and emergence of suppressor mutants at high frequency. However, differently from what was observed in E. coli, the growth of P. aeruginosa cells lacking HolD cannot be rescued by the deletion of genes for specialized DNA polymerases. We also observed that the residual growth of HolD-depleted cells is strictly dependent on homologous recombination functions, suggesting that recombination-mediated rescue of stalled replication forks is crucial to support replication by a ψ-deficient Pol III enzyme in P. aeruginosa. Full article
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Review

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15 pages, 2394 KiB  
Review
EbfC/YbaB: A Widely Distributed Nucleoid-Associated Protein in Prokaryotes
by Tamires Fernanda Vilas Boas Cordeiro, Marco Túlio Pardini Gontijo, Genesy Perez Jorge and Marcelo Brocchi
Microorganisms 2022, 10(10), 1945; https://doi.org/10.3390/microorganisms10101945 - 30 Sep 2022
Cited by 3 | Viewed by 2301
Abstract
Genomic compaction is an essential characteristic of living organisms. Nucleoid-associated proteins (NAPs) are a group of small proteins that play crucial roles in chromosome architecture and affect DNA replication, transcription, and recombination by imposing topological alterations in genomic DNA, thereby modulating global gene [...] Read more.
Genomic compaction is an essential characteristic of living organisms. Nucleoid-associated proteins (NAPs) are a group of small proteins that play crucial roles in chromosome architecture and affect DNA replication, transcription, and recombination by imposing topological alterations in genomic DNA, thereby modulating global gene expression. EbfC/YbaB was first described as a DNA-binding protein of Borrelia burgdorferi that regulates the expression of surface lipoproteins with roles in virulence. Further studies indicated that this protein binds specifically and non-specifically to DNA and colocalises with nucleoids in this bacterium. The data showed that this protein binds to DNA as a homodimer, although it can form other organised structures. Crystallography analysis indicated that the protein possesses domains responsible for protein–protein interactions and forms a “tweezer” structure probably involved in DNA binding. Moreover, sequence analysis revealed conserved motifs that may be associated with dimerisation. Structural analysis also showed that the tridimensional structure of EbfC/YbaB is highly conserved within the bacterial domain. The DNA-binding activity was observed in different bacterial species, suggesting that this protein can protect DNA during stress conditions. These findings indicate that EbfC/YbaB is a broadly distributed NAP. Here, we present a review of the existing data on this NAP. Full article
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19 pages, 1845 KiB  
Review
Molecular Regulatory Mechanisms Drive Emergent Pathogenetic Properties of Neisseria gonorrhoeae
by Ashwini Sunkavalli, Ryan McClure and Caroline Genco
Microorganisms 2022, 10(5), 922; https://doi.org/10.3390/microorganisms10050922 - 28 Apr 2022
Cited by 1 | Viewed by 3363
Abstract
Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection (STI) gonorrhea, with an estimated 87 million annual cases worldwide. N. gonorrhoeae predominantly colonizes the male and female genital tract (FGT). In the FGT, N. gonorrhoeae confronts fluctuating levels of nutrients and [...] Read more.
Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection (STI) gonorrhea, with an estimated 87 million annual cases worldwide. N. gonorrhoeae predominantly colonizes the male and female genital tract (FGT). In the FGT, N. gonorrhoeae confronts fluctuating levels of nutrients and oxidative and non-oxidative antimicrobial defenses of the immune system, as well as the resident microbiome. One mechanism utilized by N. gonorrhoeae to adapt to this dynamic FGT niche is to modulate gene expression primarily through DNA-binding transcriptional regulators. Here, we describe the major N. gonorrhoeae transcriptional regulators, genes under their control, and how these regulatory processes lead to pathogenic properties of N. gonorrhoeae during natural infection. We also discuss the current knowledge of the structure, function, and diversity of the FGT microbiome and its influence on gonococcal survival and transcriptional responses orchestrated by its DNA-binding regulators. We conclude with recent multi-omics data and modeling tools and their application to FGT microbiome dynamics. Understanding the strategies utilized by N. gonorrhoeae to regulate gene expression and their impact on the emergent characteristics of this pathogen during infection has the potential to identify new effective strategies to both treat and prevent gonorrhea. Full article
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26 pages, 2155 KiB  
Review
What Flips the Switch? Signals and Stress Regulating Extraintestinal Pathogenic Escherichia coli Type 1 Fimbriae (Pili)
by Hicham Bessaiah, Carole Anamalé, Jacqueline Sung and Charles M. Dozois
Microorganisms 2022, 10(1), 5; https://doi.org/10.3390/microorganisms10010005 - 21 Dec 2021
Cited by 11 | Viewed by 5954
Abstract
Pathogens are exposed to a multitude of harmful conditions imposed by the environment of the host. Bacterial responses against these stresses are pivotal for successful host colonization and pathogenesis. In the case of many E. coli strains, type 1 fimbriae (pili) are an [...] Read more.
Pathogens are exposed to a multitude of harmful conditions imposed by the environment of the host. Bacterial responses against these stresses are pivotal for successful host colonization and pathogenesis. In the case of many E. coli strains, type 1 fimbriae (pili) are an important colonization factor that can contribute to diseases such as urinary tract infections and neonatal meningitis. Production of type 1 fimbriae in E. coli is dependent on an invertible promoter element, fimS, which serves as a phase variation switch determining whether or not a bacterial cell will produce type 1 fimbriae. In this review, we present aspects of signaling and stress involved in mediating regulation of type 1 fimbriae in extraintestinal E. coli; in particular, how certain regulatory mechanisms, some of which are linked to stress response, can influence production of fimbriae and influence bacterial colonization and infection. We suggest that regulation of type 1 fimbriae is potentially linked to environmental stress responses, providing a perspective for how environmental cues in the host and bacterial stress response during infection both play an important role in regulating extraintestinal pathogenic E. coli colonization and virulence. Full article
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Other

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16 pages, 915 KiB  
Perspective
Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents
by Davide Roncarati, Vincenzo Scarlato and Andrea Vannini
Microorganisms 2022, 10(1), 185; https://doi.org/10.3390/microorganisms10010185 - 15 Jan 2022
Cited by 15 | Viewed by 3136
Abstract
Since the discovery of penicillin in the first half of the last century, antibiotics have become the pillars of modern medicine for fighting bacterial infections. However, pathogens resistant to antibiotic treatment have increased in recent decades, and efforts to discover new antibiotics have [...] Read more.
Since the discovery of penicillin in the first half of the last century, antibiotics have become the pillars of modern medicine for fighting bacterial infections. However, pathogens resistant to antibiotic treatment have increased in recent decades, and efforts to discover new antibiotics have decreased. As a result, it is becoming increasingly difficult to treat bacterial infections successfully, and we look forward to more significant efforts from both governments and the scientific community to research new antibacterial drugs. This perspective article highlights the high potential of bacterial transcriptional and posttranscriptional regulators as targets for developing new drugs. We highlight some recent advances in the search for new compounds that inhibit their biological activity and, as such, appear very promising for treating bacterial infections. Full article
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