scholarly journals Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

2020 ◽  
Vol 104 (24) ◽  
pp. 10409-10436
Author(s):  
Vanessa Kreling ◽  
Franco H. Falcone ◽  
Corinna Kehrenberg ◽  
Andreas Hensel
Keyword(s):  
Virulence Factors ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Bacterial Load ◽  
Phase Variation ◽  
Host Cells ◽  
Poultry Production ◽  
Secretion Systems ◽  
Effective Phase ◽  
Prevention Methods

Abstract Infections caused by bacterial species from the genus Campylobacter are one of the four main causes of strong diarrheal enteritis worldwide. Campylobacteriosis, a typical food-borne disease, can range from mild symptoms to fatal illness. About 550 million people worldwide suffer from campylobacteriosis and lethality is about 33 million p.a. This review summarizes the state of the current knowledge on Campylobacter with focus on its specific virulence factors. Using this knowledge, multifactorial prevention strategies can be implemented to reduce the prevalence of Campylobacter in the food chain. In particular, antiadhesive strategies with specific adhesion inhibitors seem to be a promising concept for reducing Campylobacter bacterial load in poultry production. Antivirulence compounds against bacterial adhesion to and/or invasion into the host cells can open new fields for innovative antibacterial agents. Influencing chemotaxis, biofilm formation, quorum sensing, secretion systems, or toxins by specific inhibitors can help to reduce virulence of the bacterium. In addition, the unusual glycosylation of the bacterium, being a prerequisite for effective phase variation and adaption to different hosts, is yet an unexplored target for combating Campylobacter sp. Plant extracts are widely used remedies in developing countries to combat infections with Campylobacter. Therefore, the present review summarizes the use of natural products against the bacterium in an attempt to stimulate innovative research concepts on the manifold still open questions behind Campylobacter towards improved treatment and sanitation of animal vectors, treatment of infected patients, and new strategies for prevention. Key points • Campylobacter sp. is a main cause of strong enteritis worldwide. • Main virulence factors: cytolethal distending toxin, adhesion proteins, invasion machinery. • Strong need for development of antivirulence compounds.

scholarly journals T6SS Mediated Stress Responses for Bacterial Environmental Survival and Host Adaptation

2021 ◽  
Vol 22 (2) ◽  
pp. 478
Author(s):  
Kai-Wei Yu ◽  
Peng Xue ◽  
Yang Fu ◽  
Liang Yang
Keyword(s):  
Protein Secretion ◽  
Stress Responses ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Host Cells ◽  
Interspecies Interactions ◽  
Type Vi Secretion System ◽  
Membrane Complex ◽  
Type Vi Secretion ◽  
Bacterial Type

The bacterial type VI secretion system (T6SS) is a protein secretion apparatus widely distributed in Gram-negative bacterial species. Many bacterial pathogens employ T6SS to compete with the host and to coordinate the invasion process. The T6SS apparatus consists of a membrane complex and an inner tail tube-like structure that is surrounded by a contractile sheath and capped with a spike complex. A series of antibacterial or antieukaryotic effectors is delivered by the puncturing device consisting of a Hcp tube decorated by the VgrG/PAAR complex into the target following the contraction of the TssB/C sheath, which often leads to damage and death of the competitor and/or host cells. As a tool for protein secretion and interspecies interactions, T6SS can be triggered by many different mechanisms to respond to various physiological conditions. This review summarizes our current knowledge of T6SS in coordinating bacterial stress responses against the unfavorable environmental and host conditions.

scholarly journals Bacterial Quorum-Quenching Lactonase Hydrolyzes Fungal Mycotoxin and Reduces Pathogenicity of Penicillium expansum—Suggesting a Mechanism of Bacterial Antagonism

2021 ◽  
Vol 7 (10) ◽  
pp. 826
Author(s):  
Shlomit Dor ◽  
Dov Prusky ◽  
Livnat Afriat-Jurnou
Keyword(s):  
Cell Wall ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Recombinant Expression ◽  
Bacterial Species ◽  
Quorum Quenching ◽  
Host Cells ◽  
Penicillium Expansum ◽  
Fungal Colonization

Penicillium expansum is a necrotrophic wound fungal pathogen that secrets virulence factors to kill host cells including cell wall degrading enzymes (CWDEs), proteases, and mycotoxins such as patulin. During the interaction between P. expansum and its fruit host, these virulence factors are strictly modulated by intrinsic regulators and extrinsic environmental factors. In recent years, there has been a rapid increase in research on the molecular mechanisms of pathogenicity in P. expansum; however, less is known regarding the bacteria–fungal communication in the fruit environment that may affect pathogenicity. Many bacterial species use quorum-sensing (QS), a population density-dependent regulatory mechanism, to modulate the secretion of quorum-sensing signaling molecules (QSMs) as a method to control pathogenicity. N-acyl homoserine lactones (AHLs) are Gram-negative QSMs. Therefore, QS is considered an antivirulence target, and enzymes degrading these QSMs, named quorum-quenching enzymes, have potential antimicrobial properties. Here, we demonstrate that a bacterial AHL lactonase can also efficiently degrade a fungal mycotoxin. The mycotoxin is a lactone, patulin secreted by fungi such as P. expansum. The bacterial lactonase hydrolyzed patulin at high catalytic efficiency, with a kcat value of 0.724 ± 0.077 s−1 and KM value of 116 ± 33.98 μM. The calculated specific activity (kcat/KM) showed a value of 6.21 × 103 s−1M−1. While the incubation of P. expansum spores with the purified lactonase did not inhibit spore germination, it inhibited colonization by the pathogen in apples. Furthermore, adding the purified enzyme to P. expansum culture before infecting apples resulted in reduced expression of genes involved in patulin biosynthesis and fungal cell wall biosynthesis. Some AHL-secreting bacteria also express AHL lactonase. Here, phylogenetic and structural analysis was used to identify putative lactonase in P. expansum. Furthermore, following recombinant expression and purification of the newly identified fungal enzyme, its activity with patulin was verified. These results indicate a possible role for patulin and lactonases in inter-kingdom communication between fungi and bacteria involved in fungal colonization and antagonism and suggest that QQ lactonases can be used as potential antifungal post-harvest treatment.

scholarly journals Impact of Salmonella enterica Type III Secretion System Effectors on the Eukaryotic Host Cell

2012 ◽  
Vol 2012 ◽  
pp. 1-36 ◽  
Author(s):  
Francisco Ramos-Morales
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Current Knowledge ◽  
Cellular Level ◽  
Host Cells ◽  
Secretion Systems ◽  
Type Iii ◽  
Cellular Processes ◽  
Type Iii Secretion Systems ◽  
Near Future

Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen’s advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided.

scholarly journals Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2015 ◽  
Vol 198 (6) ◽  
pp. 880-887 ◽  
Author(s):  
Brent S. Weber ◽  
Christian M. Harding ◽  
Mario F. Feldman
Keyword(s):  
Virulence Factors ◽  
Current Knowledge ◽  
Multidrug Resistant ◽  
Protein Glycosylation ◽  
Opportunistic Pathogens ◽  
Secretion Systems ◽  
Content Type ◽  
Bacterial Surface ◽  
Acinetobacter Pittii ◽  
New Strategies

The genusAcinetobacterencompasses multiple nosocomial opportunistic pathogens that are of increasing worldwide relevance because of their ability to survive exposure to various antimicrobial and sterilization agents. Among these,Acinetobacter baumannii,Acinetobacter nosocomialis, andAcinetobacter pittiiare the most frequently isolated in hospitals around the world. Despite the growing incidence of multidrug-resistantAcinetobacterspp., little is known about the factors that contribute to pathogenesis. New strategies for treating and managing infections caused by multidrug-resistantAcinetobacterstrains are urgently needed, and this requires a detailed understanding of the pathobiology of these organisms. In recent years, some virulence factors important forAcinetobactercolonization have started to emerge. In this review, we focus on several recently described virulence factors that act at the bacterial surface level, such as the capsule,O-linked protein glycosylation, and adhesins. Furthermore, we describe the current knowledge regarding the type II and type VI secretion systems present in these strains.

scholarly journals Generation of Virulence Factor Variants in Staphylococcus aureus Biofilms

2007 ◽  
Vol 189 (22) ◽  
pp. 7961-7967 ◽  
Author(s):  
Jeremy M. Yarwood ◽  
Kara M. Paquette ◽  
Ilya B. Tikh ◽  
Esther M. Volper ◽  
E. Peter Greenberg
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Hemolytic Activity ◽  
Bacterial Species ◽  
Phase Variation ◽  
Accessory Gene ◽  
Altered Expression ◽  
Sensing System ◽  
Accessory Gene Regulator ◽  
Different Strains

ABSTRACT Several serious diseases are caused by biofilm-associated Staphylococcus aureus. Colonial variants occur in biofilms of other bacterial species, and S. aureus variants are frequently isolated from biofilm-associated infections. Thus, we studied the generation of variants with altered expression of virulence factors in S. aureus biofilms. We observed that the number of variants found in biofilms, as measured by hemolytic activity, varied for different strains. Further study of hemolytic activity and signaling by the accessory gene regulator (Agr) quorum-sensing system in one S. aureus strain revealed three primary biofilm subpopulations: nonhemolytic (Agr deficient), hemolytic (Agr positive), and hyperhemolytic (also Agr positive). The nonhemolytic variant became the numerically dominant subpopulation in the biofilm. The nonhemolytic variant phenotype was stable and heritable, indicating a genetic perturbation, whereas the hyperhemolytic phenotype was unstable, suggesting a phase variation. Transcription profiling revealed that expression of the agr locus and many extracellular virulence factors was repressed in the nonhemolytic variant. Expression of the agr-activating gene, sarU, was also repressed in the nonhemolytic variant, suggesting one potential regulatory pathway responsible for the Agr-deficient phenotype. We suggest that the development of these variants in biofilms may have important clinical implications.

Common themes in microbial pathogenicity revisited

1997 ◽  
Vol 61 (2) ◽  
pp. 136-169
Author(s):  
B B Finlay ◽  
S Falkow
Keyword(s):  
Virulence Factors ◽  
Antigenic Variation ◽  
Regulatory Elements ◽  
Bacterial Virulence ◽  
Host Cells ◽  
Secretion Systems ◽  
Bacterial Surface ◽  
Bacterial Pathogenicity ◽  
Regulatory Circuits ◽  
Functional Factors

Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout bacterial virulence factors. For example, there are only a few general types of toxins, despite a large number of host targets. Similarly, there are only a few conserved ways to build the bacterial pilus and nonpilus adhesins used by pathogens to adhere to host substrates. Bacterial entry into host cells (invasion) is a complex mechanism. However, several common invasion themes exist in diverse microorganisms. Similarly, once inside a host cell, pathogens have a limited number of ways to ensure their survival, whether remaining within a host vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses is key to the success of a pathogen. Several common themes again are employed, including antigenic variation, camouflage by binding host molecules, and enzymatic degradation of host immune components. Most virulence factors are found on the bacterial surface or secreted into their immediate environment, yet virulence factors operate through a relatively small number of microbial secretion systems. The expression of bacterial pathogenicity is dependent upon complex regulatory circuits. However, pathogens use only a small number of biochemical families to express distinct functional factors at the appropriate time that causes infection. Finally, virulence factors maintained on mobile genetic elements and pathogenicity islands ensure that new strains of pathogens evolve constantly. Comprehension of these common themes in microbial pathogenicity is critical to the understanding and study of bacterial virulence mechanisms and to the development of new "anti-virulence" agents, which are so desperately needed to replace antibiotics.

scholarly journals Transfer of DNA from Bacteria to Eukaryotes

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Benoît Lacroix ◽  
Vitaly Citovsky
Keyword(s):  
Bartonella Henselae ◽  
Bacterial Species ◽  
Symbiotic Bacterium ◽  
Host Cells ◽  
Conjugative Plasmid ◽  
Secretion Systems ◽  
Type Iv ◽  
Conjugative Plasmid Transfer ◽  
Eukaryotic Species ◽  
Potential Applications

ABSTRACTHistorically, the members of theAgrobacteriumgenus have been considered the only bacterial species naturally able to transfer and integrate DNA into the genomes of their eukaryotic hosts. Yet, increasing evidence suggests that this ability to genetically transform eukaryotic host cells might be more widespread in the bacterial world. Indeed, analyses of accumulating genomic data reveal cases of horizontal gene transfer from bacteria to eukaryotes and suggest that it represents a significant force in adaptive evolution of eukaryotic species. Specifically, recent reports indicate that bacteria other thanAgrobacterium, such asBartonella henselae(a zoonotic pathogen),Rhizobium etli(a plant-symbiotic bacterium related toAgrobacterium), or evenEscherichia coli, have the ability to genetically transform their host cells under laboratory conditions. This DNA transfer relies on type IV secretion systems (T4SSs), the molecular machines that transport macromolecules during conjugative plasmid transfer and also during transport of proteins and/or DNA to the eukaryotic recipient cells. In this review article, we explore the extent of possible transfer of genetic information from bacteria to eukaryotic cells as well as the evolutionary implications and potential applications of this transfer.

scholarly journals Delivery of Toxins and Effectors by Bacterial Membrane Vesicles

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 845
Author(s):  
Adrian Macion ◽  
Agnieszka Wyszyńska ◽  
Renata Godlewska
Keyword(s):  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Oral Bacteria ◽  
Host Cells ◽  
Target Cells ◽  
Tissue Destruction ◽  
Secretion Systems ◽  
The Central Nervous System

Pathogenic bacteria interact with cells of their host via many factors. The surface components, i.e., adhesins, lipoproteins, LPS and glycoconjugates, are particularly important in the initial stages of colonization. They enable adhesion and multiplication, as well as the formation of biofilms. In contrast, virulence factors such as invasins and toxins act quickly to damage host cells, causing tissue destruction and, consequently, organ dysfunction. These proteins must be exported from the bacterium and delivered to the host cell in order to function effectively. Bacteria have developed a number of one- and two-step secretion systems to transport their proteins to target cells. Recently, several authors have postulated the existence of another transport system (sometimes called “secretion system type zero”), which utilizes extracellular structures, namely membrane vesicles (MVs). This review examines the role of MVs as transporters of virulence factors and the interaction of toxin-containing vesicles and other protein effectors with different human cell types. We focus on the unique ability of vesicles to cross the blood–brain barrier and deliver protein effectors from intestinal or oral bacteria to the central nervous system.

scholarly journals Secretion Systems in Gram-Negative Bacterial Fish Pathogens

2021 ◽  
Vol 12 ◽  
Author(s):  
Sophanit Mekasha ◽  
Dirk Linke
Keyword(s):  
Virulence Factors ◽  
Infection Process ◽  
Host Cells ◽  
Secretion Systems ◽  
Fish Pathogens ◽  
Gram Negative ◽  
Different Types ◽  
Single Protein ◽  
Available Information ◽  
Extracellular Environment

Bacterial fish pathogens are one of the key challenges in the aquaculture industry, one of the fast-growing industries worldwide. These pathogens rely on arsenal of virulence factors such as toxins, adhesins, effectors and enzymes to promote colonization and infection. Translocation of virulence factors across the membrane to either the extracellular environment or directly into the host cells is performed by single or multiple dedicated secretion systems. These secretion systems are often key to the infection process. They can range from simple single-protein systems to complex injection needles made from dozens of subunits. Here, we review the different types of secretion systems in Gram-negative bacterial fish pathogens and describe their putative roles in pathogenicity. We find that the available information is fragmented and often descriptive, and hope that our overview will help researchers to more systematically learn from the similarities and differences between the virulence factors and secretion systems of the fish-pathogenic species described here.

Disruption of the Francisella noatunensis orientalis pdpA gene results in virulence attenuation and protection in zebrafish

2021 ◽  
Author(s):  
John D. Hansen ◽  
Karina Ray ◽  
Po-Jui Chen ◽  
Susan Yun ◽  
Diane G. Elliott ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Bacterial Species ◽  
Acute Infection ◽  
Lethal Dose ◽  
Host Cells ◽  
Emerging Pathogens ◽  
Farmed Fish ◽  
Zebrafish Model ◽  
Virulence Attenuation

Several Francisella spp. including F. noatunensis are regarded as important emerging pathogens of wild and farmed fish. However, very few studies have investigated the virulence factors that allow these bacterial species to be pathogenic in fish. The Francisella Pathogenicity Island (FPI) is a well-described, gene-dense region encoding major virulence factors for the genus Francisella. PdpA is a member of the pathogenicity determining protein genes encoded by the FPI that are implicated in the ability of the mammalian pathogen, F. tularensis , to escape and replicate in infected host cells. Using a sacB suicide approach, we generated pdpA knockouts to address the role of PdpA as a virulence factor for F. noatunensis . Because polarity can be an issue in gene-dense regions, we generated two different marker-based mutants in opposing polarity ( Fno Δ pdpA1 and Δ pdpA2 ). Both mutants were attenuated (p<0.0001) in zebrafish challenges and displayed impaired intracellular replication (p<0.05) and cytotoxicity (p<0.05), all of which could be restored to wild-type (WT) levels by complementation for Fno Δ pdpA 1. Importantly, differences were found for bacterial burden and induction of acute phase and pro-inflammatory genes for Fno Δ pdpA 1 and Δ pdpA 2 compared to WT during acute infection. In addition, neither mutant resulted in significant histopathological changes. Finally, immunization with Fno Δ pdpA1 led to protection (p<0.012) against an acute lethal-dose 40 challenge with WT Fno in the zebrafish model of infection. Taken together, this study further demonstrates physiological similarities within the genus Francisella relative to their phylogenetic relationships and the utility of zebrafish for addressing virulence factors for the genus.

Sign in / Sign up

Export Citation Format

Share Document