species, including opportunistic pathogens in the complex (Bcc), have genes to produce contact-dependent growth inhibition (CDI) system proteins. CDI is a phenomenon in which Gram-negative bacteria use the toxic C terminus of a polymorphic surface-exposed exoprotein, BcpA, to inhibit the growth of susceptible bacteria upon direct cell-cell contact. Production of a small immunity protein, BcpI, prevents autoinhibition. Although CDI systems appear widespread in Gram-negative bacteria, their function has been primarily examined in several model species. Here we demonstrate that genes encoding predicted CDI systems in Bcc species exhibit considerable diversity. We also show that , which causes pulmonary infections in patients with cystic fibrosis, expresses genes that encode two CDI systems, both of which appear distinct from the typical -type CDI system. Each system can mediate intrastrain interbacterial competition and contributes to bacterial adherence. Surprisingly, the immunity-protein-encoding gene of CDI system 1 could be mutated without obvious deleterious effects. We also show that nonpathogenic uses CDI to control growth during coculture, providing one of the first examples of interspecies CDI and suggesting that CDI systems could be manipulated to develop therapeutic strategies targeting Bcc pathogens. Competition among bacteria affects microbial colonization of environmental niches and host organisms, particularly during polymicrobial infections. The Bcc is a group of environmental bacteria that can cause life-threatening opportunistic infections in patients who have cystic fibrosis or are immunocompromised. Understanding the mechanisms used by these bacterial pathogens to compete with one another may lead to the development of more effective therapies. Findings presented here demonstrate that a Bcc species, , produces functional CDI system proteins and that growth of this pathogen can be controlled by CDI system proteins produced by neighboring cells.
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http://dx.doi.org/10.1128/JB.00012-19 | DOI Listing |
Cell Host Microbe
December 2024
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St Louis, St. Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
Gastrointestinal colonization by Clostridioides difficile is common in healthcare settings and ranges in presentation from asymptomatic carriage to lethal C. difficile infection (CDI). We used a systems biology approach to investigate why patients colonized with C.
View Article and Find Full Text PDFGut Microbes
December 2025
Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France.
Clinical symptoms of infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of with higher relapse rates.
View Article and Find Full Text PDFCell Syst
December 2024
Imprint Labs, LLC, New York, NY, USA; Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address:
The adaptive immune system holds invaluable information on past and present immune responses in the form of B and T cell receptor sequences, but we are limited in our ability to decode this information. Machine learning approaches are under active investigation for a range of tasks relevant to understanding and manipulating the adaptive immune receptor repertoire, including matching receptors to the antigens they bind, generating antibodies or T cell receptors for use as therapeutics, and diagnosing disease based on patient repertoires. Progress on these tasks has the potential to substantially improve the development of vaccines, therapeutics, and diagnostics, as well as advance our understanding of fundamental immunological principles.
View Article and Find Full Text PDFCommun Dis Intell (2018)
December 2024
World Health Organisation Collaborating Centre for STI and AMR, Sydney and Neisseria Reference Laboratory, Department of Microbiology, NSW Health Pathology, The Prince of Wales Hospital, Randwick, 2031, NSW Australia.
In Australia, both probable and laboratory-confirmed cases of invasive meningococcal disease (IMD) are reported to the National Notifiable Diseases Surveillance System (NNDSS). When compared to 2022, the number of IMD notifications in 2023 increased by 14% to 143. Laboratory confirmation of IMD occurred in 140/143 (98%) of these cases, with 64% (90/140) diagnosed by bacterial culture and 36% (50/140) by nucleic acid amplification testing.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Pharmacology and Therapeutics, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GL, UK.
() is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood from patients with infection.
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