Proc Natl Acad Sci U S A
November 2024
Quorum sensing (QS) is a cell-to-cell communication process that enables bacteria to coordinate group behaviors. In colonies, a program of spatial-temporal cell death is among the QS-controlled traits. Cell death occurs in two phases, first along the colony rim, and subsequently, at the colony center.
View Article and Find Full Text PDFBacterial colonies composed of genetically identical individuals can diversify to yield variant cells with distinct genotypes. Variant outgrowth manifests as sectors. Here, we show that Type VI secretion system (T6SS)-driven cell death in Vibrio cholerae colonies imposes a selective pressure for the emergence of variant strains that can evade T6SS-mediated killing.
View Article and Find Full Text PDFBacteria orchestrate collective behaviors using the cell-cell communication process called quorum sensing (QS). QS relies on the synthesis, release, and group-wide detection of small molecules called autoinducers. In Vibrio cholerae, a multicellular community aggregation program occurs in liquid, during the stationary phase, and in the high-cell-density QS state.
View Article and Find Full Text PDFQuorum sensing is a chemical communication process in which bacteria use the production, release, and detection of signal molecules called autoinducers to orchestrate collective behaviors. The human pathogen requires quorum sensing to infect the small intestine. There, encounters the absence of oxygen and the presence of bile salts.
View Article and Find Full Text PDFBacterial biofilms represent a basic form of multicellular organization that confers survival advantages to constituent cells. The sequential stages of cell ordering during biofilm development have been studied in the pathogen and model biofilm-former It is unknown how spatial trajectories of individual cells and the collective motions of many cells drive biofilm expansion. We developed dual-view light-sheet microscopy to investigate the dynamics of biofilm development from a founder cell to a mature three-dimensional community.
View Article and Find Full Text PDFThe taphylococcal espiratory egulator (SrrAB) modulates energy metabolism in Studies have suggested that regulated protein catabolism facilitates energy homeostasis. Regulated proteolysis in is achieved through protein complexes composed of a peptidase (ClpQ or ClpP) in association with an AAA family ATPase (typically, ClpC or ClpX). In the present report, we tested the hypothesis that SrrAB regulates a Clp complex to facilitate energy homeostasis in Strains deficient in one or more Clp complexes were attenuated for growth in the presence of puromycin, which causes enrichment of misfolded proteins.
View Article and Find Full Text PDFIn response to the increasingly problematic emergence of antibiotic resistance, novel strategies for combating pathogenic bacteria are being investigated. Targeting the agr quorum sensing system, which regulates expression of virulence in Staphylococcus aureus, is one potentially useful approach for combating drug-resistant pathogens that has not yet been fully explored. A previously published study of a fragment screen resulted in the identification of five compound fragments that interact with the DNA-binding domain of the response regulator AgrA from S.
View Article and Find Full Text PDFComprehending biology at the molecular and systems levels is predicated upon understanding the functions of proteins. Proteins are typically composed of one or more functional moieties termed domains. Members of Bacteria, Eukarya, and Archaea utilize proteins containing a domain of unknown function (DUF) 59.
View Article and Find Full Text PDFBiofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic.
View Article and Find Full Text PDFremains a causative agent for morbidity and mortality worldwide. This is in part a result of antimicrobial resistance, highlighting the need to uncover novel antibiotic targets and to discover new therapeutic agents. In the present study, we explored the possibility that iron-sulfur (Fe-S) cluster synthesis is a viable antimicrobial target.
View Article and Find Full Text PDFDuring times of environmental insult, Bacillus subtilis undergoes developmental changes leading to biofilm formation, sporulation and competence. Each of these states is regulated in part by the phosphorylated form of the master response regulator Spo0A (Spo0A∼P). The phosphorylation state of Spo0A is controlled by a multi-component phosphorelay.
View Article and Find Full Text PDFBiofilms are communities of microorganisms attached to a surface or each other. Biofilm-associated cells are the etiologic agents of recurrent infections. Infected human tissues are hypoxic or anoxic.
View Article and Find Full Text PDFThe SrrAB two-component regulatory system (TCRS) positively influences the transcription of genes involved in aerobic respiration in response to changes in respiratory flux. Hydrogen peroxide (H2O2) can arise as a byproduct of spontaneous interactions between dioxygen and components of respiratory pathways. H2O2 damages cellular factors including protein associated iron-sulfur cluster prosthetic groups.
View Article and Find Full Text PDFThe rising problem of antimicrobial resistance in Staphylococcus aureus necessitates the discovery of novel therapeutic targets for small-molecule intervention. A major obstacle of drug discovery is identifying the target of molecules selected from high-throughput phenotypic assays. Here, we show that the toxicity of a small molecule termed '882 is dependent on the constitutive activity of the S.
View Article and Find Full Text PDFStaphylococcus aureus SufT is composed solely of the domain of unknown function 59 (DUF59) and has a role in the maturation of iron-sulphur (Fe-S) proteins. We report that SufT is essential for S. aureus when growth is heavily reliant upon lipoamide-utilizing enzymes, but dispensable when this reliance is decreased.
View Article and Find Full Text PDFProteins containing DUF59 domains have roles in iron-sulfur (FeS) cluster assembly and are widespread throughout Eukarya, Bacteria, and Archaea. However, the function(s) of this domain is unknown. Staphylococcus aureus SufT is composed solely of a DUF59 domain.
View Article and Find Full Text PDFMolecular cloning is a cornerstone of modern biology laboratories. However, traditional cloning can be time-consuming and problematic. We outline herein a method that utilizes the endogenous gap repair system of yeast cells to clone and assemble DNA constructs.
View Article and Find Full Text PDFThe acquisition and metabolism of iron (Fe) by the human pathogen Staphylococcus aureus is critical for disease progression. S. aureus requires Fe to synthesize inorganic cofactors called iron-sulfur (Fe-S) clusters, which are required for functional Fe-S proteins.
View Article and Find Full Text PDFCloning by homologous recombination (HR) in Saccharomyces cerevisiae is an extremely efficient and cost-effective alternative to other methods of recombinant DNA technologies. Unfortunately, it is incompatible with all the various specialized plasmids currently used in microbiology and biomedical research laboratories, and is therefore, not widely adopted. In an effort to dramatically improve the versatility of yeast gap-repair cloning and make it compatible with any DNA plasmid, we demonstrate that by simply including a yeast-cloning cassette (YCC) that contains the 2-micron origin of replication (2μm ori) and the ura3 gene for selection, multiple DNA fragments can be assembled into any DNA vector.
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