Regulated Proteolysis in Vibrio cholerae Allowing Rapid Adaptation to Stress Conditions

Pennetzdorfer, Nina; Lembke, Mareike; Preßler, Katharina; Matson, Jyl S.; Reidl, Joachim; Schild, Stefan

doi:10.3389/fcimb.2019.00214

Cited by 24 publications

(20 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By targeting transcription factors for proteolysis, bacteria can modulate their gene expression profiles in response to new environmental stimuli. Several studies have demonstrated that the avirulent phenotypes associated with protease-deficient mutants are due in large part to such aberrant gene regulation [ 41 , 42 , 43 ]. Interestingly, we found that the clpA and clpS mutant strains exhibit formidable phenotypic changes including alterations to cell size, shape and especially in clpA , a possible defect in bacterial separation during replication.…”

Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

et al. 2021

View full text Add to dashboard Cite

Acinetobacter baumannii has emerged as a significant opportunistic Gram-negative pathogen and causative agent of nosocomial pneumonia especially in immunocompromised individuals in intensive care units. Recent advances to understand the contribution and function of A. baumannii virulence factors in its pathogenesis have begun to elucidate how this bacterium interacts with immune cells and its interesting mechanisms for multi-antibiotic resistance. Taking advantage of the availability of the A. baumannii AB5075 transposon mutant library, we investigated the impact of the A. baumannii Clp genes, which encode for a chaperone-protease responsible for the degradation of misfolded proteins, on bacterial virulence in a model of pneumonia using C57BL/6 mice and survival within J774.16 macrophage-like cells. Clp-protease A. baumannii mutants exhibit decreased virulence in rodents, high phagocytic cell-mediated killing and reduced biofilm formation. Capsular staining showed evidence of encapsulation in A. baumannii AB5075 and Clp-mutant strains. Surprisingly, clpA and clpS mutants displayed irregular cell morphology, which may be important in the biofilm structural deficiencies observed in these strains. Interestingly, clpA showed apical-like growth, proliferation normally observed in filamentous fungi. These findings provide new information regarding A. baumannii pathogenesis and may be important for the development of therapies intended at reducing morbidity and mortality associated with this remarkable pathogen.

show abstract

Section: Discussionmentioning

confidence: 99%

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, one possibility is that stress-dependent regulation of ClpAP indirectly regulates Pchb. It has also been hypothesized that V. cholerae makes use of proteolysis machines to rapidly respond to changes in their environment; namely, the transition from the human gut to the aquatic environment after infection (43). ClpAP acting as an activator of Pchb may be a way for cells to rapidly induce expression of a locus that is not important in the human gut, but is useful for survival in its aquatic reservoir.…”

Section: Discussionmentioning

confidence: 99%

Species-specific quorum sensing represses the chitobiose utilization locus inVibrio cholerae

Klancher

Newman

Ball

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractThe marine facultative pathogen Vibrio cholerae forms complex multicellular communities on the chitinous shells of crustacean zooplankton in its aquatic reservoir. V. cholerae-chitin interactions are critical for the growth, evolution, and waterborne transmission of cholera. This is due, in part, to chitin-induced changes in gene expression in this pathogen. Here, we sought to identify factors that influence chitin-induced expression of one locus, the chitobiose utilization operon (chb), which is required for the uptake and catabolism of the chitin disaccharide. Through a series of genetic screens, we identified that the master regulator of quorum sensing, HapR, is a direct repressor of the chb operon. We also found that the levels of HapR in V. cholerae are regulated by the ClpAP protease. Furthermore, we show that the canonical quorum sensing cascade in V. cholerae regulates chb expression in a HapR-dependent manner. Through this analysis we found that signaling via the species-specific autoinducer CAI-1, but not the inter-species autoinducer AI-2, influences chb expression. This phenomenon of species-specific regulation may enhance the fitness of this pathogen in its environmental niche.ImportanceIn nature, bacteria live in multicellular and multispecies communities. Microbial species can sense the density and composition of their community through chemical cues using a process called quorum sensing (QS). The marine pathogen Vibrio cholerae is found in communities on the chitinous shells of crustaceans in its aquatic reservoir. V. cholerae interactions with chitin are critical for the survival, evolution, and waterborne transmission of this pathogen. Here, we show that V. cholerae uses QS to regulate the expression of one locus required for V. cholerae-chitin interactions.

show abstract

“…DegS is a serine protease located in the periplasm of bacteria, and is an important component of the bacterial response to external pressure (Kim, 2015). The degS is now seen as an essential gene whose indispensable function is to provide active σ E activity (Alba et al, 2001; Pennetzdorfer et al, 2019). However, the biological function and global regulatory network of DegS in V. cholerae remain limited.…”

Section: Discussionmentioning

confidence: 99%

“…The cAMP-CRP complex can bind to the promoter region of rpoS and further stimulate the transcription of this gene (Cheng & Sun, 2009). RpoS is an alternative sigma factor (σ S ) of RNA polymerase that plays a role in the general stress response and modulation of the stationary phase (Weber et al, 2005; Pennetzdorfer et al, 2019). In V. cholerae , rpoS mutants are highly sensitive to hydrogen peroxide and are involved in colonization during the infection process and in the dissolution of biofilms (Merrell et al, 2000; Müller et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the effects of a degS mutant on the growth of Vibrio cholerae and the global regulatory function of degS by RNA sequencing

Huang

Chen

et al. 2019

PeerJ

View full text Add to dashboard Cite

BackgroundDegS is a periplasmic serine protease that is considered to be the initiator of the σE stress response pathway, and this protein plays an important role in the regulation of the stress response in E. coli. However, knowledge of the biological function and global regulatory network of DegS in Vibrio cholerae remains limited. In this study, we aimed to characterize the molecular functions and further investigate the regulatory network of degS in V. cholerae.MethodsA deletion mutant of degS was constructed in the V. cholerae HN375 strain. Bacterial colony morphology was observed by a plate-based growth experiment, and bacterial growth ability was observed by a growth curve experiment. High-throughput RNA sequencing (RNA-Seq) technology was used to analyze the differential transcriptomic profiles between the wild-type and degS mutant strains. Gene ontology (GO), pathway analysis and Gene-Act-network analysis were performed to explore the main functions of the differentially expressed genes. Quantitative real-time PCR (qRT-PCR) was performed to validate the reliability and accuracy of the RNA-Seq analysis. The complementation experiments were used to test the roles of degS and ropS in the small colony degS mutant phenotype.ResultsWhen degS was deleted, the degS mutant exhibited smaller colonies on various media and slower growth than the wild-type strain. A total of 423 differentially expressed genes were identified, including 187 genes that were upregulated in the degS mutant compared to the wild-type strain and 236 genes that were relatively downregulated. GO categories and pathway analysis showed that many differentially expressed genes were associated with various cellular metabolic pathways and the cell cycle. Furthermore, Gene-Act network analysis showed that many differentially expressed genes were involved in cellular metabolic pathways and bacterial chemotaxis. The cAMP-CRP-RpoS signaling pathway and the LuxPQ signal transduction system were also affected by the degS mutant. The expression patterns of nine randomly selected differentially expressed genes were consistent between the qRT-PCR and RNA-seq results. The complementation experiments showed that the small colony degS mutant phenotype could be partially restored by complementation with the pBAD24-degS or pBAD24-rpoS plasmid.DiscussionThese results suggest that the degS gene is important for normal growth of V. cholerae. Some of the differentially expressed genes were involved in various cellular metabolic processes and the cell cycle, which may be associated with bacterial growth. Several new degS-related regulatory networks were identified. In addition, our results suggested that the cAMP-CRP-RpoS signaling pathway may be involved in the small colony degS mutant phenotype. Overall, we believe that these transcriptomic data will serve as useful genetic resources for research on the functions of degS in V. cholerae.

show abstract

Regulated Proteolysis in Vibrio cholerae Allowing Rapid Adaptation to Stress Conditions

Cited by 24 publications

References 106 publications

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

Acinetobacter baumannii Strains Deficient in the Clp Chaperone-Protease Genes Have Reduced Virulence in a Murine Model of Pneumonia

Species-specific quorum sensing represses the chitobiose utilization locus inVibrio cholerae

Exploration of the effects of a degS mutant on the growth of Vibrio cholerae and the global regulatory function of degS by RNA sequencing

Contact Info

Product

Resources

About