International Journal of Molecular Sciences

Editorial

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6 pages, 212 KiB

Open AccessEditorial

Microbial Virulence Factors

by Jorge H. Leitão

Int. J. Mol. Sci. 2020, 21(15), 5320; https://doi.org/10.3390/ijms21155320 - 27 Jul 2020

Cited by 57 | Viewed by 9570

Abstract

Microbial virulence factors encompass a wide range of molecules produced by pathogenic microorganisms, enhancing their ability to evade their host defenses and cause disease [...] Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

Research

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15 pages, 1875 KiB

Open AccessArticle

Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence in Candida glabrata

by Mafalda Cavalheiro, Daniela Romão, Rui Santos, Dalila Mil-Homens, Pedro Pais, Catarina Costa, Mónica Galocha, Diana Pereira, Azusa Takahashi-Nakaguchi, Hiroji Chibana, Arsénio M. Fialho and Miguel C. Teixeira

Int. J. Mol. Sci. 2021, 22(3), 1376; https://doi.org/10.3390/ijms22031376 - 29 Jan 2021

Cited by 5 | Viewed by 3301

Abstract

Candida glabrata is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF CAGL0L10912g) is described as a new determinant [...] Read more.

Candida glabrata is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF CAGL0L10912g) is described as a new determinant of virulence in C. glabrata, using the infection model Galleria mellonella. The CgTPO4 gene was found to be required for the C. glabrata ability to kill G. mellonella. The transporter encoded by this gene is also necessary for antimicrobial peptide (AMP) resistance, specifically against histatin-5. Interestingly, G. mellonella’s AMP expression was found to be strongly activated in response to C. glabrata infection, suggesting AMPs are a key antifungal defense. CgTpo4 was also found to be a plasma membrane exporter of polyamines, especially spermidine, suggesting that CgTpo4 is able to export polyamines and AMPs, thus conferring resistance to both stress agents. Altogether, this study presents the polyamine exporter CgTpo4 as a determinant of C. glabrata virulence, which acts by protecting the yeast cells from the overexpression of AMPs, deployed as a host defense mechanism. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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30 pages, 3034 KiB

Open AccessArticle

Lon Protease Is Important for Growth under Stressful Conditions and Pathogenicity of the Phytopathogen, Bacterium Dickeya solani

by Donata Figaj, Paulina Czaplewska, Tomasz Przepióra, Patrycja Ambroziak, Marta Potrykus and Joanna Skorko-Glonek

Int. J. Mol. Sci. 2020, 21(10), 3687; https://doi.org/10.3390/ijms21103687 - 23 May 2020

Cited by 8 | Viewed by 4459

Abstract

The Lon protein is a protease implicated in the virulence of many pathogenic bacteria, including some plant pathogens. However, little is known about the role of Lon in bacteria from genus Dickeya. This group of bacteria includes important potato pathogens, with the [...] Read more.

The Lon protein is a protease implicated in the virulence of many pathogenic bacteria, including some plant pathogens. However, little is known about the role of Lon in bacteria from genus Dickeya. This group of bacteria includes important potato pathogens, with the most aggressive species, D. solani. To determine the importance of Lon for pathogenicity and response to stress conditions of bacteria, we constructed a D. solani Δlon strain. The mutant bacteria showed increased sensitivity to certain stress conditions, in particular osmotic and high-temperature stresses. Furthermore, qPCR analysis showed an increased expression of the lon gene in D. solani under these conditions. The deletion of the lon gene resulted in decreased motility, lower activity of secreted pectinolytic enzymes and finally delayed onset of blackleg symptoms in the potato plants. In the Δlon cells, the altered levels of several proteins, including virulence factors and proteins associated with virulence, were detected by means of Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) analysis. These included components of the type III secretion system and proteins involved in bacterial motility. Our results indicate that Lon protease is important for D. solani to withstand stressful conditions and effectively invade the potato plant. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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23 pages, 18913 KiB

Open AccessArticle

The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption

by Pravil Pokharel, Juan Manuel Díaz, Hicham Bessaiah, Sébastien Houle, Alma Lilián Guerrero-Barrera and Charles M. Dozois

Int. J. Mol. Sci. 2020, 21(9), 3047; https://doi.org/10.3390/ijms21093047 - 26 Apr 2020

Cited by 12 | Viewed by 4808

Abstract

TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on [...] Read more.

TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract. Some SPATEs produced by pathogenic E. coli are known to breach the bladder epithelium. The capacity of these newly described SPATEs to alter bladder epithelial cells and the role of the serine protease active site were investigated. All three SPATE proteins were internalized by bladder epithelial cells and altered the distribution of actin cytoskeleton. Sha and TagC were also shown to degrade mucin and gelatin respectively. Inactivation of the serine catalytic site in each of these SPATEs did not affect secretion of the SPATEs from bacterial cells, but abrogated entry into epithelial cells, cytotoxicity, and proteolytic activity. Thus, our results show that the serine catalytic triad of these proteins is required for internalization in host cells, actin disruption, and degradation of host substrates such as mucin and gelatin. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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14 pages, 1717 KiB

Open AccessArticle

Antibiotic Resistance, Virulence Factors, Phenotyping, and Genotyping of Non-Escherichia coli Enterobacterales from the Gut Microbiota of Healthy Subjects

by Alberto Amaretti, Lucia Righini, Francesco Candeliere, Eliana Musmeci, Francesca Bonvicini, Giovanna Angela Gentilomi, Maddalena Rossi and Stefano Raimondi

Int. J. Mol. Sci. 2020, 21(5), 1847; https://doi.org/10.3390/ijms21051847 - 7 Mar 2020

Cited by 33 | Viewed by 5654

Abstract

Non-Escherichia coli Enterobacterales (NECE) can colonize the human gut and may present virulence determinants and phenotypes that represent severe heath concerns. Most information is available for virulent NECE strains, isolated from patients with an ongoing infection, while the commensal NECE population of [...] Read more.

Non-Escherichia coli Enterobacterales (NECE) can colonize the human gut and may present virulence determinants and phenotypes that represent severe heath concerns. Most information is available for virulent NECE strains, isolated from patients with an ongoing infection, while the commensal NECE population of healthy subjects is understudied. In this study, 32 NECE strains were isolated from the feces of 20 healthy adults. 16S rRNA gene sequencing and mass spectrometry attributed the isolates to Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Enterobacter kobei, Citrobacter freundii, Citrobacter amalonaticus, Cronobacter sp., and Hafnia alvei, Morganella morganii, and Serratia liquefaciens. Multiplex PCR revealed that K. pneumoniae harbored virulence genes for adhesins (mrkD, ycfM, and kpn) and enterobactin (entB) and, in one case, also for yersiniabactin (ybtS, irp1, irp2, and fyuA). Virulence genes were less numerous in the other NECE species. Biofilm formation was spread across all the species, while curli and cellulose were mainly produced by Citrobacter and Enterobacter. Among the most common antibiotics, amoxicillin-clavulanic acid was the sole against which resistance was observed, only Klebsiella strains being susceptible. The NECE inhabiting the intestine of healthy subjects have traits that may pose a health threat, taking into account the possibility of horizontal gene transfer. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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21 pages, 3995 KiB

Open AccessArticle

Interspecies Outer Membrane Vesicles (OMVs) Modulate the Sensitivity of Pathogenic Bacteria and Pathogenic Yeasts to Cationic Peptides and Serum Complement

by Justyna Roszkowiak, Paweł Jajor, Grzegorz Guła, Jerzy Gubernator, Andrzej Żak, Zuzanna Drulis-Kawa and Daria Augustyniak

Int. J. Mol. Sci. 2019, 20(22), 5577; https://doi.org/10.3390/ijms20225577 - 8 Nov 2019

Cited by 34 | Viewed by 5933

Abstract

The virulence of bacterial outer membrane vesicles (OMVs) contributes to innate microbial defense. Limited data report their role in interspecies reactions. There are no data about the relevance of OMVs in bacterial-yeast communication. We hypothesized that model Moraxella catarrhalis OMVs may orchestrate the [...] Read more.

The virulence of bacterial outer membrane vesicles (OMVs) contributes to innate microbial defense. Limited data report their role in interspecies reactions. There are no data about the relevance of OMVs in bacterial-yeast communication. We hypothesized that model Moraxella catarrhalis OMVs may orchestrate the susceptibility of pathogenic bacteria and yeasts to cationic peptides (polymyxin B) and serum complement. Using growth kinetic curve and time-kill assay we found that OMVs protect Candida albicans against polymyxin B-dependent fungicidal action in combination with fluconazole. We showed that OMVs preserve the virulent filamentous phenotype of yeasts in the presence of both antifungal drugs. We demonstrated that bacteria including Haemophilus influenza, Acinetobacter baumannii, and Pseudomonas aeruginosa coincubated with OMVs are protected against membrane targeting agents. The high susceptibility of OMV-associated bacteria to polymyxin B excluded the direct way of protection, suggesting rather the fusion mechanisms. High-performance liquid chromatography-ultraviolet spectroscopy (HPLC-UV) and zeta-potential measurement revealed a high sequestration capacity (up to 95%) of OMVs against model cationic peptide accompanied by an increase in surface electrical charge. We presented the first experimental evidence that bacterial OMVs by sequestering of cationic peptides may protect pathogenic yeast against combined action of antifungal drugs. Our findings identify OMVs as important inter-kingdom players. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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16 pages, 3112 KiB

Open AccessArticle

A Novel Effector Protein of Apple Proliferation Phytoplasma Disrupts Cell Integrity of Nicotiana spp. Protoplasts

by Cecilia Mittelberger, Hagen Stellmach, Bettina Hause, Christine Kerschbamer, Katja Schlink, Thomas Letschka and Katrin Janik

Int. J. Mol. Sci. 2019, 20(18), 4613; https://doi.org/10.3390/ijms20184613 - 18 Sep 2019

Cited by 11 | Viewed by 3967

Abstract

Effector proteins play an important role in the virulence of plant pathogens such as phytoplasma, which are the causative agents of hundreds of different plant diseases. The plant hosts comprise economically relevant crops such as apples (Malus × domestica), which can [...] Read more.

Effector proteins play an important role in the virulence of plant pathogens such as phytoplasma, which are the causative agents of hundreds of different plant diseases. The plant hosts comprise economically relevant crops such as apples (Malus × domestica), which can be infected by ‘Candidatus Phytoplasma mali’ (P. mali), a highly genetically dynamic plant pathogen. As the result of the genetic and functional analyses in this study, a new putative P. mali effector protein was revealed. The so-called “Protein in Malus Expressed 2” (PME2), which is expressed in apples during P. mali infection but not in the insect vector, shows regional genetic differences. In a heterologous expression assay using Nicotiana benthamiana and Nicotiana occidentalis mesophyll protoplasts, translocation of both PME2 variants in the cell nucleus was observed. Overexpression of the effector protein affected cell integrity in Nicotiana spp. protoplasts, indicating a potential role of this protein in pathogenic virulence. Interestingly, the two genetic variants of PME2 differ regarding their potential to manipulate cell integrity. However, the exact function of PME2 during disease manifestation and symptom development remains to be further elucidated. Aside from the first description of the function of a novel effector of P. mali, the results of this study underline the necessity for a more comprehensive description and understanding of the genetic diversity of P. mali as an indispensable basis for a functional understanding of apple proliferation disease. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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16 pages, 2267 KiB

Open AccessArticle

Comparative Integrated Omics Analysis of the Hfq Regulon in Bordetella pertussis

by Ana Dienstbier, Fabian Amman, Daniel Štipl, Denisa Petráčková and Branislav Večerek

Int. J. Mol. Sci. 2019, 20(12), 3073; https://doi.org/10.3390/ijms20123073 - 24 Jun 2019

Cited by 10 | Viewed by 3613

Abstract

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large [...] Read more.

Bordetella pertussis is a Gram-negative strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Previously, we have shown that RNA chaperone Hfq is required for virulence of B. pertussis. Furthermore, microarray analysis revealed that a large number of genes are affected by the lack of Hfq. This study represents the first attempt to characterize the Hfq regulon in bacterial pathogen using an integrative omics approach. Gene expression profiles were analyzed by RNA-seq and protein amounts in cell-associated and cell-free fractions were determined by LC-MS/MS technique. Comparative analysis of transcriptomic and proteomic data revealed solid correlation (r² = 0.4) considering the role of Hfq in post-transcriptional control of gene expression. Importantly, our study confirms and further enlightens the role of Hfq in pathogenicity of B. pertussis as it shows that Δhfq strain displays strongly impaired secretion of substrates of Type III secretion system (T3SS) and substantially reduced resistance to serum killing. On the other hand, significantly increased production of proteins implicated in transport of important metabolites and essential nutrients observed in the mutant seems to compensate for the physiological defect introduced by the deletion of the hfq gene. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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10 pages, 1849 KiB

Open AccessArticle

Relation of the pdxB-usg-truA-dedA Operon and the truA Gene to the Intracellular Survival of Salmonella enterica Serovar Typhimurium

by Xiaowen Yang, Jiawei Wang, Ziyan Feng, Xiangjian Zhang, Xiangguo Wang and Qingmin Wu

Int. J. Mol. Sci. 2019, 20(2), 380; https://doi.org/10.3390/ijms20020380 - 17 Jan 2019

Cited by 6 | Viewed by 3391

Abstract

Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red [...] Read more.

Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red recombination system was used to construct gene deletion strains and to investigate whether the identified operon was related to intracellular survival. The pdxB-usg-truA-dedA operon enhanced the intracellular survival of S. enterica by resisting the oxidative environment and the usg and truA gene expression was induced by H₂O₂. Moreover, the genes in this operon (except for dedA) contributed to virulence in mice. These findings indicate that the pdxB-usg-truA-dedA operon functions in resistance to oxidative environments during intracellular survival and is required for in vivo S. enterica virulence. This study provides insight toward a better understand of the characteristics of intracellular pathogens and explores the gene modules involved in their intracellular survival. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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19 pages, 2991 KiB

Open AccessArticle

Proteomics Analysis of SsNsd1-Mediated Compound Appressoria Formation in Sclerotinia sclerotiorum

by Jingtao Li, Xianghui Zhang, Le Li, Jinliang Liu, Yanhua Zhang and Hongyu Pan

Int. J. Mol. Sci. 2018, 19(10), 2946; https://doi.org/10.3390/ijms19102946 - 27 Sep 2018

Cited by 14 | Viewed by 3925

Abstract

Sclerotinia sclerotiorum (Lib.) de Bary is a devastating necrotrophic fungal pathogen attacking a broad range of agricultural crops. In this study, although the transcript accumulation of SsNsd1, a GATA-type IVb transcription factor, was much lower during the vegetative hyphae stage, its mutants completely [...] Read more.

Sclerotinia sclerotiorum (Lib.) de Bary is a devastating necrotrophic fungal pathogen attacking a broad range of agricultural crops. In this study, although the transcript accumulation of SsNsd1, a GATA-type IVb transcription factor, was much lower during the vegetative hyphae stage, its mutants completely abolished the development of compound appressoria. To further elucidate how SsNsd1 influenced the appressorium formation, we conducted proteomics-based analysis of the wild-type and ΔSsNsd1 mutant by two-dimensional electrophoresis (2-DE). A total number of 43 differentially expressed proteins (≥3-fold change) were observed. Of them, 77% were downregulated, whereas 14% were upregulated. Four protein spots fully disappeared in the mutants. Further, we evaluated these protein sequences by mass spectrometry analysis of the peptide mass and obtained functionally annotated 40 proteins, among which only 17 proteins (38%) were identified to have known functions including energy production, metabolism, protein fate, stress response, cellular organization, and cell growth and division. However, the remaining 23 proteins (56%) were characterized as hypothetical proteins among which four proteins (17%) were predicted to contain the signal peptides. In conclusion, the differentially expressed proteins identified in this study shed light on the ΔSsNsd1 mutant-mediated appressorium deficiency and can be used in future investigations to better understand the signaling mechanisms of SsNsd1 in S. sclerotiorum. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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18 pages, 4118 KiB

Open AccessArticle

Discovery of lahS as a Global Regulator of Environmental Adaptation and Virulence in Aeromonas hydrophila

by Yuhao Dong, Yao Wang, Jin Liu, Shuiyan Ma, Furqan Awan, Chengping Lu and Yongjie Liu

Int. J. Mol. Sci. 2018, 19(9), 2709; https://doi.org/10.3390/ijms19092709 - 11 Sep 2018

Cited by 7 | Viewed by 3645

Abstract

Aeromonas hydrophila is an important aquatic microorganism that can cause fish hemorrhagic septicemia. In this study, we identified a novel LysR family transcriptional regulator (LahS) in the A. hydrophila Chinese epidemic strain NJ-35 from a library of 947 mutant strains. The deletion of [...] Read more.

Aeromonas hydrophila is an important aquatic microorganism that can cause fish hemorrhagic septicemia. In this study, we identified a novel LysR family transcriptional regulator (LahS) in the A. hydrophila Chinese epidemic strain NJ-35 from a library of 947 mutant strains. The deletion of lahS caused bacteria to exhibit significantly decreased hemolytic activity, motility, biofilm formation, protease production, and anti-bacterial competition ability when compared to the wild-type strain. In addition, the determination of the fifty percent lethal dose (LD₅₀) in zebrafish demonstrated that the lahS deletion mutant (ΔlahS) was highly attenuated in virulence, with an approximately 200-fold increase in LD₅₀ observed as compared with that of the wild-type strain. However, the ΔlahS strain exhibited significantly increased antioxidant activity (six-fold). Label-free quantitative proteome analysis resulted in the identification of 34 differentially expressed proteins in the ΔlahS strain. The differentially expressed proteins were involved in flagellum assembly, metabolism, redox reactions, and cell density induction. The data indicated that LahS might act as a global regulator to directly or indirectly regulate various biological processes in A. hydrophila NJ-35, contributing to a greater understanding the pathogenic mechanisms of A. hydrophila. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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Review

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14 pages, 11583 KiB

Open AccessReview

Bacterial Actin-Specific Endoproteases Grimelysin and Protealysin as Virulence Factors Contributing to the Invasive Activities of Serratia

by Sofia Khaitlina, Ekaterina Bozhokina, Olga Tsaplina and Tatiana Efremova

Int. J. Mol. Sci. 2020, 21(11), 4025; https://doi.org/10.3390/ijms21114025 - 4 Jun 2020

Cited by 14 | Viewed by 2976

Abstract

The article reviews the discovery, properties and functional activities of new bacterial enzymes, proteases grimelysin (ECP 32) of Serratia grimesii and protealysin of Serratia proteamaculans, characterized by both a highly specific “actinase” activity and their ability to stimulate bacterial invasion. Grimelysin cleaves [...] Read more.

The article reviews the discovery, properties and functional activities of new bacterial enzymes, proteases grimelysin (ECP 32) of Serratia grimesii and protealysin of Serratia proteamaculans, characterized by both a highly specific “actinase” activity and their ability to stimulate bacterial invasion. Grimelysin cleaves the only polypeptide bond Gly42-Val43 in actin. This bond is not cleaved by any other proteases and leads to a reversible loss of actin polymerization. Similar properties were characteristic for another bacterial protease, protealysin. These properties made grimelysin and protealysin a unique tool to study the functional properties of actin. Furthermore, bacteria Serratia grimesii and Serratia proteamaculans, producing grimelysin and protealysin, invade eukaryotic cells, and the recombinant Escherichia coli expressing the grimelysin or protealysins gene become invasive. Participation of the cellular c-Src and RhoA/ROCK signaling pathways in the invasion of eukaryotic cells by S. grimesii was shown, and involvement of E-cadherin in the invasion has been suggested. Moreover, membrane vesicles produced by S. grimesii were found to contain grimelysin, penetrate into eukaryotic cells and increase the invasion of bacteria into eukaryotic cells. These data indicate that the protease is a virulence factor, and actin can be a target for the protease upon its translocation into the host cell. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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37 pages, 1539 KiB

Open AccessReview

From Gene to Protein—How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection

by Lea Denzer, Horst Schroten and Christian Schwerk

Int. J. Mol. Sci. 2020, 21(10), 3730; https://doi.org/10.3390/ijms21103730 - 25 May 2020

Cited by 33 | Viewed by 8528

Abstract

Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also [...] Read more.

Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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28 pages, 1185 KiB

Open AccessReview

Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

by Rosanna Herold, Horst Schroten and Christian Schwerk

Int. J. Mol. Sci. 2019, 20(21), 5393; https://doi.org/10.3390/ijms20215393 - 29 Oct 2019

Cited by 28 | Viewed by 15143

Abstract

Infections of the central nervous system (CNS) are still a major cause of morbidity and mortality worldwide. Traversal of the barriers protecting the brain by pathogens is a prerequisite for the development of meningitis. Bacteria have developed a variety of different strategies to [...] Read more.

Infections of the central nervous system (CNS) are still a major cause of morbidity and mortality worldwide. Traversal of the barriers protecting the brain by pathogens is a prerequisite for the development of meningitis. Bacteria have developed a variety of different strategies to cross these barriers and reach the CNS. To this end, they use a variety of different virulence factors that enable them to attach to and traverse these barriers. These virulence factors mediate adhesion to and invasion into host cells, intracellular survival, induction of host cell signaling and inflammatory response, and affect barrier function. While some of these mechanisms differ, others are shared by multiple pathogens. Further understanding of these processes, with special emphasis on the difference between the blood–brain barrier and the blood–cerebrospinal fluid barrier, as well as virulence factors used by the pathogens, is still needed. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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33 pages, 988 KiB

Open AccessReview

Pathogenicity and Virulence of Trueperella pyogenes: A Review

by Magdalena Rzewuska, Ewelina Kwiecień, Dorota Chrobak-Chmiel, Magdalena Kizerwetter-Świda, Ilona Stefańska and Małgorzata Gieryńska

Int. J. Mol. Sci. 2019, 20(11), 2737; https://doi.org/10.3390/ijms20112737 - 4 Jun 2019

Cited by 117 | Viewed by 11641

Abstract

Bacteria from the species Trueperella pyogenes are a part of the biota of skin and mucous membranes of the upper respiratory, gastrointestinal, or urogenital tracts of animals, but also, opportunistic pathogens. T. pyogenes causes a variety of purulent infections, such as metritis, mastitis, [...] Read more.

Bacteria from the species Trueperella pyogenes are a part of the biota of skin and mucous membranes of the upper respiratory, gastrointestinal, or urogenital tracts of animals, but also, opportunistic pathogens. T. pyogenes causes a variety of purulent infections, such as metritis, mastitis, pneumonia, and abscesses, which, in livestock breeding, generate significant economic losses. Although this species has been known for a long time, many questions concerning the mechanisms of infection pathogenesis, as well as reservoirs and routes of transmission of bacteria, remain poorly understood. Pyolysin is a major known virulence factor of T. pyogenes that belongs to the family of cholesterol-dependent cytolysins. Its cytolytic activity is associated with transmembrane pore formation. Other putative virulence factors, including neuraminidases, extracellular matrix-binding proteins, fimbriae, and biofilm formation ability, contribute to the adhesion and colonization of the host tissues. However, data about the pathogen–host interactions that may be involved in the development of T. pyogenes infection are still limited. The aim of this review is to present the current knowledge about the pathogenic potential and virulence of T. pyogenes. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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25 pages, 1040 KiB

Open AccessReview

Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin

by Mónica Galocha, Pedro Pais, Mafalda Cavalheiro, Diana Pereira, Romeu Viana and Miguel C. Teixeira

Int. J. Mol. Sci. 2019, 20(9), 2345; https://doi.org/10.3390/ijms20092345 - 11 May 2019

Cited by 60 | Viewed by 10284

Abstract

Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful [...] Read more.

Candida albicans and Candida glabrata are the two most prevalent etiologic agents of candidiasis worldwide. Although both are recognized as pathogenic, their choice of virulence traits is highly divergent. Indeed, it appears that these different approaches to fungal virulence may be equally successful in causing human candidiasis. In this review, the virulence mechanisms employed by C. albicans and C. glabrata are analyzed, with emphasis on the differences between the two systems. Pathogenesis features considered in this paper include dimorphic growth, secreted enzymes and signaling molecules, and stress resistance mechanisms. The consequences of these traits in tissue invasion, biofilm formation, immune system evasion, and macrophage escape, in a species dependent manner, are discussed. This review highlights the observation that C. albicans and C. glabrata follow different paths leading to a similar outcome. It also highlights the lack of knowledge on some of the specific mechanisms underlying C. glabrata pathogenesis, which deserve future scrutiny. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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19 pages, 3605 KiB

Open AccessReview

Catching a SPY: Using the SpyCatcher-SpyTag and Related Systems for Labeling and Localizing Bacterial Proteins

by Daniel Hatlem, Thomas Trunk, Dirk Linke and Jack C. Leo

Int. J. Mol. Sci. 2019, 20(9), 2129; https://doi.org/10.3390/ijms20092129 - 30 Apr 2019

Cited by 83 | Viewed by 23275

Abstract

The SpyCatcher-SpyTag system was developed seven years ago as a method for protein ligation. It is based on a modified domain from a Streptococcus pyogenes surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide [...] Read more.

The SpyCatcher-SpyTag system was developed seven years ago as a method for protein ligation. It is based on a modified domain from a Streptococcus pyogenes surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide bond between the side chains of a lysine in SpyCatcher and an aspartate in SpyTag. This technology has been used, among other applications, to create covalently stabilized multi-protein complexes, for modular vaccine production, and to label proteins (e.g., for microscopy). The SpyTag system is versatile as the tag is a short, unfolded peptide that can be genetically fused to exposed positions in target proteins; similarly, SpyCatcher can be fused to reporter proteins such as GFP, and to epitope or purification tags. Additionally, an orthogonal system called SnoopTag-SnoopCatcher has been developed from an S. pneumoniae pilin that can be combined with SpyCatcher-SpyTag to produce protein fusions with multiple components. Furthermore, tripartite applications have been produced from both systems allowing the fusion of two peptides by a separate, catalytically active protein unit, SpyLigase or SnoopLigase. Here, we review the current state of the SpyCatcher-SpyTag and related technologies, with a particular emphasis on their use in vaccine development and in determining outer membrane protein localization and topology of surface proteins in bacteria. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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19 pages, 287 KiB

Open AccessReview

Coagulase-Negative Staphylococci Pathogenomics

by Xavier Argemi, Yves Hansmann, Kevin Prola and Gilles Prévost

Int. J. Mol. Sci. 2019, 20(5), 1215; https://doi.org/10.3390/ijms20051215 - 11 Mar 2019

Cited by 131 | Viewed by 12119

Abstract

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus [...] Read more.

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch’s postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis, S. haemolyticus, S. saprophyticus, S. capitis, and S. lugdunensis. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

21 pages, 613 KiB

Open AccessReview

Small Noncoding Regulatory RNAs from Pseudomonas aeruginosa and Burkholderia cepacia Complex

by Tiago Pita, Joana R. Feliciano and Jorge H. Leitão

Int. J. Mol. Sci. 2018, 19(12), 3759; https://doi.org/10.3390/ijms19123759 - 27 Nov 2018

Cited by 28 | Viewed by 6095

Abstract

Cystic fibrosis (CF) is the most life-limiting autosomal recessive disorder in Caucasians. CF is characterized by abnormal viscous secretions that impair the function of several tissues, with chronic bacterial airway infections representing the major cause of early decease of these patients. Pseudomonas aeruginosa [...] Read more.

Cystic fibrosis (CF) is the most life-limiting autosomal recessive disorder in Caucasians. CF is characterized by abnormal viscous secretions that impair the function of several tissues, with chronic bacterial airway infections representing the major cause of early decease of these patients. Pseudomonas aeruginosa and bacteria from the Burkholderia cepacia complex (Bcc) are the leading pathogens of CF patients’ airways. A wide array of virulence factors is responsible for the success of infections caused by these bacteria, which have tightly regulated responses to the host environment. Small noncoding RNAs (sRNAs) are major regulatory molecules in these bacteria. Several approaches have been developed to study P. aeruginosa sRNAs, many of which were characterized as being involved in the virulence. On the other hand, the knowledge on Bcc sRNAs remains far behind. The purpose of this review is to update the knowledge on characterized sRNAs involved in P. aeruginosa virulence, as well as to compile data so far achieved on sRNAs from the Bcc and their possible roles on bacteria virulence. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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11 pages, 992 KiB

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Targeting Pseudomonas aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential

by Giuseppantonio Maisetta, Lucia Grassi, Semih Esin, Esingül Kaya, Andrea Morelli, Dario Puppi, Martina Piras, Federica Chiellini, Massimo Pifferi and Giovanna Batoni

Int. J. Mol. Sci. 2020, 21(1), 69; https://doi.org/10.3390/ijms21010069 - 20 Dec 2019

Cited by 9 | Viewed by 3262

Abstract

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, [...] Read more.

In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium. Full article

(This article belongs to the Special Issue Microbial Virulence Factors)

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