Vibrio cholerae hemagglutinin(HA)/protease: An extracellular metalloprotease with multiple pathogenic activities

Benítez, Jorge A.; Silva, Alcino J.

doi:10.1016/j.toxicon.2016.03.003

Cited by 54 publications

(53 citation statements)

References 99 publications

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“…HapA, the major soluble protease produced by the cholera bacterium, is a member of the M4 neutral peptidase family that displays significant amino acid sequence homology to P. aeruginosa elastase and Bacillus thermoproteolyticus thermolysin (27). This soluble protease is present in the matrix of biofilms formed under laboratory conditions (28).…”

Section: Introductionmentioning

confidence: 99%

Flagellar motility, extracellular proteases and Vibrio cholerae detachment from abiotic and biotic surfaces

Mewborn

Benítez

Silva

2017

Microbial Pathogenesis

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Vibrio cholerae of serogroups O1 and O139, the causative agent of Asiatic cholera, continues to be a major global health threat. This pathogen utilizes substratum-specific pili to attach to distinct surfaces in the aquatic environment and the human small intestine and detaches when conditions become unfavorable. Both attachment and detachment are critical to bacterial environmental survival, pathogenesis and disease transmission. However, the factors that promote detachment are less understood. In this study, we examine the role of flagellar motility and hemagglutinin/protease (HapA) in vibrio detachment from a non-degradable abiotic surface and from the suckling mouse intestine. Flagellar motility facilitated V. cholerae detachment from abiotic surfaces. HapA had no effect on the stability of biofilms formed on abiotic surfaces despite representing > 50 % of the proteolytic activity present in the extracellular matrix. We developed a balanced lethal plasmid system to increase the bacterial cyclic diguanylate (c-di-GMP) pool late in infection, a condition that represses motility and HapA expression. Increasing the c-di-GMP pool enhanced V. cholerae colonization of the suckling mouse intestine. The c-di-GMP effect was fully abolished in hapA isogenic mutants. These results suggest that motility facilitates detachment in a substratum-independent manner. Instead, HapA appears to function as a substratum-specific detachment factor.

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Section: Introductionmentioning

confidence: 99%

Flagellar motility, extracellular proteases and Vibrio cholerae detachment from abiotic and biotic surfaces

Mewborn

Benítez

Silva

2017

Microbial Pathogenesis

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“…A couple of neutral metalloproteases from pathogenic bacteria are related to bacillolysin and thermolysin [29][30][31]40]. As expected, zinc-binding residues and other catalytic amino acids are highly conserved between these proteins, despite moderate overall sequence identity and the lack of bound calcium ions.…”

Section: Discussionmentioning

confidence: 98%

Destructive twisting of neutral metalloproteases: the catalysis mechanism of the Dispase autolysis‐inducing protein from Streptomyces mobaraensis DSM 40487

et al. 2018

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The Dispase autolysis-inducing protein (DAIP) is produced by Streptomyces mobaraensis to disarm neutral metalloproteases by decomposition. The absence of a catalytic protease domain led to the assumption that the seven-bladed β-propeller protein DAIP causes structural modifications, thereby triggering autolysis. Determination of protein complexes consisting of DAIP and thermolysin or DAIP and a nonfunctional E138A bacillolysin variant supported this postulation. Protein twisting was indicated by DAIP-mediated inhibition of thermolysin while bacillolysin underwent immediate autolysis under the same conditions. Interestingly, an increase in SYPRO orange fluorescence allowed tracking of the fast degradation process. Similarly rapid autolysis of thermolysin mediated by DAIP was only observed upon the addition of amphiphilic compounds, which probably amplify the induced structural changes. DAIP further caused degradation of FITC-labeled E138A bacillolysin by trypsin, as monitored by a linear decrease in fluorescence polarization. The kinetic model, calculated from the obtained data, suggested a three-step mechanism defined by (a) fast DAIP-metalloprotease complex formation, (b) slower DAIP-mediated protein twisting, and (c) fragmentation. These results were substantiated by crystallized DAIP attached to a C-terminal helix fragment of thermolysin. Structural superposition of the complex with thermolysin is indicative of a conformational change upon binding to DAIP. Importantly, the majority of metalloproteases, also including homologs from various pathogens, are highly conserved at the autolysis-prone peptide bonds, suggesting their susceptibility to DAIP-mediated decomposition, which may offer opportunities for pharmaceutical applications. DATABASES: The atomic coordinates and structure factors (PDB ID: 6FHP) have been deposited in the Protein Data Bank (http://www.pdb.org/). ENZYMES: Aureolysin, EC 3.4.24.29; bacillolysin (Dispase, Gentlyase), EC 3.4.24.28; lasB (elastase), EC 3.4.24.4; subtilisin, EC 3.4.21.62; thermolysin, EC 3.4.24.27; transglutaminase, EC 2.3.2.13; trypsin, EC 3.4.21.4; vibriolysin (hemagglutinin(HA)/protease), EC 3.4.24.25.

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“…2A) (69,71). HAP is a HapR-regulated metalloprotease that cleaves proteins in the biofilm matrix when the cell density increases, thus possibly facilitating bacterial cell dispersal in the late stages of colonization (58,59,72,73). In the aquatic environment, HAP digests the gelatinous matrix of chironomid egg masses, mediates associations with cyanobacteria, and aids in dissolving organic matter, thereby releasing nutrients for V. cholerae cells (Fig.…”

Section: Quorum Sensingmentioning

confidence: 99%

Environmental Role of Pathogenic Traits in Vibrio cholerae

2018

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is a natural inhabitant of aquatic ecosystems. Some strains of can colonize the human host and cause cholera, a profuse watery diarrhea. The major pathogenicity factors and virulence regulators of are either encoded in mobile genetic elements acquired in the environment (e.g. pathogenicity islands or lysogenic phages) or in the core genome. Several lines of evidence indicate that the emergence of numerous virulence traits of occurred in its natural environment due to biotic and abiotic pressures. Here, we discuss the connection between the human host and the potential ecological role of these virulent traits. Unraveling these connections will help us understand the emergence of this organism and other facultative bacterial pathogens.

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Vibrio cholerae hemagglutinin(HA)/protease: An extracellular metalloprotease with multiple pathogenic activities

Cited by 54 publications

References 99 publications

Flagellar motility, extracellular proteases and Vibrio cholerae detachment from abiotic and biotic surfaces

Flagellar motility, extracellular proteases and Vibrio cholerae detachment from abiotic and biotic surfaces

Destructive twisting of neutral metalloproteases: the catalysis mechanism of the Dispase autolysis‐inducing protein from Streptomyces mobaraensis DSM 40487

Environmental Role of Pathogenic Traits in Vibrio cholerae

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