Special Issue "Gene Regulation in Biofilms"

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: 30 September 2020.

Special Issue Editor

Prof. Dr. Jan-Ulrik Dahl
Guest Editor
Illinois State University School of Biological Sciences PO Box 4120 Normal, IL 61790
Interests: Biofilm formation; Redox Biology; Oxidative Stress; Thiols; Sulfur; Iron-sulfur cluster; Polyphosphate; Pseudomonas aeruginosa; uropathogenic E. coli; Gram-negative Bacteria; Reactive Oxygen Species; Virulence factors; Antibiotic Resistance; Bacterial Pathogenicity; Bacterial Stress Response

Special Issue Information

Dear Colleagues,

For a long time, bacteria have only been considered to live a planktonic lifestyle as floating or actively swimming single organisms. Over the past five decades, however, it has become increasingly clear that many bacteria can live in multicellular communities, e.g., through the formation of stress-resistant biofilms. Biofilm formation is a tightly regulated process found both in Gram-negative and Gram-positive bacteria that involves several steps: (i) attachment of planktonic bacteria to biotic or abiotic surfaces; (ii) microcolony formation through replication and cell-to-cell adhesion; (iii) development into highly organized mature biofilms embedded in an extracellular polymeric matrix; and (iv) dispersal of biofilm cells by switching to the planktonic state. In comparison with their planktonic counterparts, biofilm cells have been shown to have significantly better protection from the host immune response and up to 1000-fold less susceptibility to various antimicrobial agents due to their reduced metabolic rates, differential expression of efflux pumps, the presence of a self-produced extracellular polymeric matrix, and reduced uptake/increased sequestration of antimicrobial compounds. Hence, the ability of bacteria to form stress-resistant biofilms represents an exceptional adaption strategy for their survival in hostile environments, including human hosts. The biofilm lifestyle of many pathogens is currently recognized as the underlying cause for many difficult-to-treat persistent infections and represents a major challenge in hospital settings. To accomplish the exceptionally complex differentiation of planktonic bacteria into biofilm communities in a highly concerted fashion, bacteria employ numerous sophisticated regulatory mechanisms involving finely altered gene expression. A near-ubiquitous second messenger that coordinates diverse aspects of bacterial growth and behavior, including motility, virulence, and the transition of planktonic to biofilm lifestyle, is c-di-GMP. Elevated levels of c-di-GMP result in increased production of extracellular matrix components, adhesive pili, non-fimbrial adhesins, extracellular DNA, and other biofilm-associated characteristics such as impaired motility. Quorum sensing regulates cell density and induces changes in gene expression depending on the availability of signaling molecules and small non-coding RNAs. RNA-binding proteins, toxin-antitoxin systems, and riboswitches represent additional regulatory mechanisms that are known to be involved in biofilm regulation.

This Special Issue in Pathogens on “Gene Regulation in Biofilms” will focus on the latest state-of-art developments and current knowledge in the field of gene regulation in bacterial biofilms, both in vitro and in vivo. We invite authors to submit research or review manuscripts covering these important molecular aspects of biofilm regulation.

Prof. Dr. Jan-Ulrik Dahl
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • bacterial biofilms
  • antimicrobial resistance
  • quorum sensing
  • c-di-GMP
  • sigma factor
  • two-component regulatory systems
  • bacterial stress response
  • pathogen

Published Papers (1 paper)

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Open AccessArticle
CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems
Pathogens 2020, 9(1), 53; https://doi.org/10.3390/pathogens9010053 - 10 Jan 2020
Salmonella is recognized as one of the most common microbial pathogens worldwide. The bacterium contains the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, providing adaptive immunity against invading foreign nucleic acids. Previous studies suggested that certain bacteria employ the Cas proteins [...] Read more.
Salmonella is recognized as one of the most common microbial pathogens worldwide. The bacterium contains the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems, providing adaptive immunity against invading foreign nucleic acids. Previous studies suggested that certain bacteria employ the Cas proteins of CRISPR-Cas systems to target their own genes, which also alters the virulence during invasion of mammals. However, whether CRISPR-Cas systems in Salmonella have similar functions during bacterial invasion of host cells remains unknown. Here, we systematically analyzed the genes that are regulated by Cas3 in a type I-E CRISPR-Cas system and the virulence changes due to the deletion of cas3 in Salmonella enterica serovar Enteritidis. Compared to the cas3 gene wild-type (cas3 WT) Salmonella strain, cas3 deletion upregulated the lsrFGBE genes in lsr (luxS regulated) operon related to quorum sensing (QS) and downregulated biofilm-forming-related genes and Salmonella pathogenicity island 1 (SPI-1) genes related to the type three secretion system (T3SS). Consistently, the biofilm formation ability was downregulated in the cas3 deletion mutant (Δcas3). The bacterial invasive and intracellular capacity of Δcas3 to host cells was also reduced, thereby increasing the survival of infected host cells and live chickens. By the transcriptome-wide screen (RNA-Seq), we found that the cas3 gene impacts a series of genes related to QS, the flagellum, and SPI-1-T3SS system, thereby altering the virulence phenotypes. As QS SPI-1-T3SS and CRISPR-Cas systems are widely distributed in the bacteria kingdom, our findings extend our understanding of virulence regulation and pathogenicity in mammalian hosts for Salmonella and potentially other bacteria. Full article
(This article belongs to the Special Issue Gene Regulation in Biofilms)
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