Bacterial serine protease HtrA as a promising new target for antimicrobial therapy?

Weßler, Silja; Schneider, Gisbert; Backert, Steffen

doi:10.1186/s12964-017-0162-5

Cited by 43 publications

(43 citation statements)

References 64 publications

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“…This is especially relevant for the skin environment which is nutrient-poor and enriched with lipids and proteins (Chen et al, 2018). In particular, proteases are nature's powerful tools in mediating catabolism of proteins (López-Otín and Bond, 2008), where degradation of specific protein targets can function in important processes such as nutrient acquisition and skin surface adherence (Naglik et al, 2003;Wessler et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Identification of Malassezia furfur Secreted Aspartyl Protease 1 (MfSAP1) and Its Role in Extracellular Matrix Degradation

Poh

Goh

Fan

et al. 2020

Front. Cell. Infect. Microbiol.

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Malassezia is the most abundant eukaryotic microbial genus on human skin. Similar to many human-residing fungi, Malassezia has high metabolic potential and secretes a plethora of hydrolytic enzymes that can potentially modify and structure the external skin environment. Here we show that the dominant secreted Malassezia protease isolated from cultured Malassezia furfur is an aspartyl protease that is secreted and active at all phases of culture growth. We observed that this protease, herein named as MfSAP1 (M. furfur secreted aspartyl protease 1) has a broader substrate cleavage profile and higher catalytic efficiency than the previously reported protease homolog in Malassezia globosa. We demonstrate that MfSAP1 is capable of degrading a wide range of human skin associated extracellular matrix (ECM) proteins and ECM isolated directly from keratinocytes and fibroblasts. Using a 3-D wound model with primary keratinocytes grown on human de-epidermized dermis, we show that MfSAP1 protease can potentially interfere with wound re-epithelization in an acute wound model. Taken together, our work demonstrates that Malassezia proteases have host-associated substrates and play important roles in cutaneous wound healing.

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Section: Introductionmentioning

confidence: 99%

Identification of Malassezia furfur Secreted Aspartyl Protease 1 (MfSAP1) and Its Role in Extracellular Matrix Degradation

Poh

Goh

Fan

et al. 2020

Front. Cell. Infect. Microbiol.

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“…In a similar fashion, mutations in the htrA gene of S. pneumonie (Musa et al 2004), Klebsiella pneumonie (Cortes et al 2002) and Listeria monocytogenes 10403S (Wonderling et al 2004) did have no effect in the growth rates at 37ºC, but did reduce the growth and/or survival rates at higher temperatures and in other bacteria as mentioned by Wessler (Wessler et al 2017). In L. monocytogenes 10403S the sensitivity to high osmolarity was also increased in the mutant.…”

Section: Discussionmentioning

confidence: 65%

“…Y. pseudotuberculosis HtrA protein shares the proteolytic and the two PDZ domains with its orthologues from E. coli (Wessler et al 2017), Legionella fallonii, and Thermotoga maritime (Hansen and Hilgenfeld, 2013). A regulatory role for the PDZ domains has been demonstrated for HtrA and DegS (Krojer et al 2010), but currently, there is no evidence for a similar regulation of the Y. pseudotuberculosis HtrA protein.…”

Section: Discussionmentioning

confidence: 99%

The htrA Gene Plays an Important role During Yersinia Pseudotuberculosis Growth at High Temperature

Garduño

Urzúa

Sotres

et al. 2020

Preprint

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htrA is a gene coding for the stress inducible HtrA protein, identified as a temperature stress response protein in several Gram positive and Gram negative bacteria. Growth rates at several temperatures (30ºC, 37ºC and 42ºC) were compared for Yersinia pseudotuberculosis YPIII wild strain and the isogenic mutant 1YPIII (htrA::Km), which was obtained by insertion of a kanamycin resistance cassette into the htrA gene.Y. pseudotuberculosis 1YPIII growth rates did not differ from the Y. pseudotuberculosis wild strain growth rates when cultivated at 30°C, which is consistent with a non-essential role for the HtrA protein at this temperature. However, 1YPIII mutant strain growth rate decreased by 18.73% at 37°C, and by 60.14% at 42°C, as compared to the Y. pseudotuberculosis YPIII wild strain growth rate. HtrA complementation in the strain 1YPIII/pAHTRA46 suppressed the differences in growth rates. Immunoblot analysis confirmed the absence of the HtrA protein in the 1YPIII mutant strain at any of the growth temperatures under analysis. In silico predictions were obtained for the three-dimensional structure of amino acid sequence belonging to HtrA from Y. pseudotuberculosis YPIII, Yersinia pestis CO92, using the protein data bank structure 1KY9:B from Escherichia coli, as template. The model's quality was found to be acceptable. Southern blot analysis shows a single htrA gene signal. These data indicate that the unique htrA gene in Y. pseudotuberculosis YPIII is required for the adaptive response of this species to high temperatures and although it is not a pathogenicity factor, it can be targeted by antibiotics.

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“…Several additional DAPs identified at the 1.5‐fold‐change threshold also were associated with adhesion or stress response. More abundant DAPs included a MOP superfamily polysaccharide flippase transporter, an Eps operon transcriptional regulator associated in other strains with EPS production and virulence, and HtrA, a serine protease associated with survival under stress and with extracellular matrix adhesion proteins . Interestingly, DAPs at the 1.5‐fold‐change level that were less abundant in biofilms (i.e., more abundant in planktonic cultures) included cell division protein FtsA, a protein that, along with FtsZ, is essential for bacterial cytokinesis, as well as DnaD and RecX, two proteins associated with DNA replication or repair.…”

Section: Resultsmentioning

confidence: 99%

Quantitative proteomic analysis of Lactobacillus delbrueckii ssp. lactis biofilms

et al. 2018

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Lactic acid is a valuable organic acid that can be produced by fermentation of renewable sugar. Lactate productivity can be increased by retaining cells within the reactor, enabling continuous operation with higher cell concentrations. Biofilms are an inexpensive cell immobilization method. While much is known about the differences in physiology and metabolism of pathogenic biofilms, biofilms relevant to industrial processes are less characterized. The goal of this study was to identify metabolic features of biofilm metabolism of Lactobacillus delbrueckii ssp. lactis using quantitative proteomics. Compounds in biofilm samples negatively affected LC–MS/MS performance, indicating the importance of sample precipitation. Among other differences, proteins associated with metabolic processes such as fatty acid biosynthesis and metal oxidation were more abundant in biofilm cells, as were proteins associated with stress. This is the first proteomic study of a Lactobacillus species in biofilms with relevance to industrial biotechnology. © 2018 American Institute of Chemical Engineers AIChE J, 64: 4341–4350, 2018

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Bacterial serine protease HtrA as a promising new target for antimicrobial therapy?

Cited by 43 publications

References 64 publications

Identification of Malassezia furfur Secreted Aspartyl Protease 1 (MfSAP1) and Its Role in Extracellular Matrix Degradation

Identification of Malassezia furfur Secreted Aspartyl Protease 1 (MfSAP1) and Its Role in Extracellular Matrix Degradation

The htrA Gene Plays an Important role During Yersinia Pseudotuberculosis Growth at High Temperature

Quantitative proteomic analysis of Lactobacillus delbrueckii ssp. lactis biofilms

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