bacterial virulence
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2022 ◽  
Vol 23 (2) ◽  
pp. 670
Author(s):  
Nolan Neville ◽  
Nathan Roberge ◽  
Zongchao Jia

Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.


Plants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Namgyu Kim ◽  
Gil Han ◽  
Hyejung Jung ◽  
Hyun-Hee Lee ◽  
Jungwook Park ◽  
...  

Burkholderia glumae are bacteria pathogenic to rice plants that cause a disease called bacterial panicle blight (BPB) in rice panicles. BPB, induced by B. glumae, causes enormous economic losses to the rice agricultural industry. B. glumae also causes bacterial disease in other crops because it has various virulence factors, such as toxins, proteases, lipases, extracellular polysaccharides, bacterial motility, and bacterial secretion systems. In particular, B. glumae BGR1 harbors type VI secretion system (T6SS) with functionally distinct roles: the prokaryotic targeting system and the eukaryotic targeting system. The functional activity of T6SS requires 13 core components and T6SS accessory proteins, such as adapters containing DUF2169, DUF4123, and DUF1795 domains. There are two genes, bglu_1g23320 and bglu_2g07420, encoding the DUF2169 domain-containing protein in the genome of B. glumae BGR1. bglu_2g07420 belongs to the gene cluster of T6SS group_5 in B. glumae BGR1, whereas bglu_1g23320 does not belong to any T6SS gene cluster in B. glumae BGR1. T6SS group_5 of B. glumae BGR1 is involved in bacterial virulence in rice plants. The DUF2169 domain-containing protein with a single domain can function by itself; however, Δu1g23320 showed no attenuated virulence in rice plants. In contrast, Δu2g07420DUF2169 and Δu2g07420PPR did exhibit attenuated virulence in rice plants. These results suggest that the pentapeptide repeats region of the C-terminal additional domain, as well as the DUF2169 domain, is required for complete functioning of the DUF2169 domain-containing protein encoded by bglu_2g07420. bglu_2g07410, which encodes the pentapeptide repeats protein, composed of only the pentapeptide repeats region, is located downstream of bglu_2g07420. Δu2g07410 also shows attenuated virulence in rice plants. This finding suggests that the pentapeptide repeats protein, encoded by bglu_2g07410, is involved in bacterial virulence. This study is the first report that the DUF2169 domain-containing protein and pentapeptide repeats protein are involved in bacterial virulence to the rice plants as T6SS accessory proteins, encoded in the gene cluster of the T6SS group_5.


Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 56
Author(s):  
Fatema Rahman ◽  
Imin Wushur ◽  
Nabin Malla ◽  
Ove Alexander Høgmoen Åstrand ◽  
Pål Rongved ◽  
...  

Inhibition of bacterial virulence is believed to be a new treatment option for bacterial infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc metalloproteases, matrix metalloprotease-9 (MMP-9) and matrix metalloprotease-14 (MMP-14). These compounds have nitrogen or sulfur as putative donor atoms for zinc chelation. In general, the compounds showed stronger inhibition of MMP-14 and PLN than of the other enzymes, with Ki values in the lower μM range. Except for DPA, none of the compounds showed significantly stronger inhibition of the virulence factors than of the human zinc metalloproteases. TPA and Zn230 were the only compounds that inhibited all five zinc metalloproteinases with a Ki value in the lower μM range. The thiophene compounds gave weak or no inhibition. Docking indicated that some of the compounds coordinated zinc by one oxygen atom from a hydroxyl or carbonyl group, or by oxygen atoms both from a hydroxyl group and a carbonyl group, and not by pyridine nitrogen as in DPA and TPA.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Luo ◽  
Lidong Wang ◽  
Lei Song ◽  
Zhao-Qing Luo

Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates a wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because of its essential role in immunity, the ubiquitin network is a common target of infectious agents, which have evolved various effective strategies to hijack and co-opt ubiquitin signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one such example; it utilizes a large cohort of virulence factors called effectors to modulate diverse cellular processes, resulting in the formation a compartment called the Legionella-containing vacuole (LCV) that supports its replication. Many of these effectors function to re-orchestrate ubiquitin signaling with distinct biochemical activities. In this review, we highlight recent progress in the mechanism of action of L. pneumophila effectors involved in ubiquitination and discuss their roles in bacterial virulence and host cell biology.


2021 ◽  
Vol 63 (4) ◽  
pp. 62-65
Author(s):  
Nguyen Thuan Thien Truong ◽  
◽  
The Hao Nguyen ◽  
Cong Chinh Bui ◽  
Thi Thu Hoai Nguyen ◽  
...  

Vibrio parahaemolyticus is the main causative agent of acute hepatopancreatic necrosis disease (AHPND) in shrimp. This study aimed to investigate how shrimp extracts affect the growth and virulence of an AHPND-causative strain known as V. parahaemolyticus XN9. To this end, the bacteria was cultured in media containing 3% extract of each of five shrimp types and their growth kinetics were compared against that from bacteria grown in brain-heart infusion (BHI) media. Eight-hour growth curves were constructed using the plate-counting method. The activity of five extracellular enzymes that contribute to bacterial virulence was examined using the agar-based method. The results showed that V. parahaemolyticus XN9’s growth was strongly enhanced in all five shrimp extract media with the highest increase (25% greater than the BHI medium) found in the giant tiger prawn extract. Additionally, all the shrimp extracts boosted the extracellular enzymatic activity of V. parahaemolyticus XN9, although to different extents. In summary, the shrimp extracts, particularly that from the prawns, not only promoted the viability and growth of V. parahaemolyticus XN9 but also its extracellular enzymatic activities.


2021 ◽  
Vol 9 (12) ◽  
pp. 2514
Author(s):  
Michael McCarthy ◽  
Monica Goncalves ◽  
Hannah Powell ◽  
Blake Morey ◽  
Madison Turner ◽  
...  

The anti-virulence strategy is designed to prevent bacterial virulence factors produced by pathogenic bacteria from initiating and sustaining an infection. One family of bacterial virulence factors is the mono-ADP-ribosyltransferase toxins, which are produced by pathogens as tools to compromise the target host cell. These toxins are bacterial enzymes that exploit host cellular NAD+ as the donor substrate to modify an essential macromolecule acceptor target in the host cell. This biochemical reaction modifies the target macromolecule (often protein or DNA) and functions in a binary fashion to turn the target activity on or off by blocking or impairing a critical process or pathway in the host. A structural biology approach to the anti-virulence method to neutralize the cytotoxic effect of these factors requires the search and design of small molecules that bind tightly to the enzyme active site and prevent catalytic function essentially disarming the pathogen. This method requires a high-resolution structure to serve as the model for small molecule inhibitor development, which illuminates the path to drug development. This alternative strategy to antibiotic therapy represents a paradigm shift that may circumvent multi-drug resistance in the offending microbe through anti-virulence therapy. In this report, the rationale for the anti-virulence structural approach will be discussed along with recent efforts to apply this method to treat honey bee diseases using natural products.


2021 ◽  
Author(s):  
Julien S. Luneau ◽  
Aude Cerutti ◽  
Brice Roux ◽  
Sébastien Carrère ◽  
Marie‐Françoise Jardinaud ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Kira L. Tomlinson ◽  
Alice S. Prince ◽  
Tania Wong Fok Lung

Pseudomonas aeruginosa and Staphylococcus aureus are both opportunistic pathogens that are frequently associated with chronic lung infections. While bacterial virulence determinants are critical in initiating infection, the metabolic flexibility of these bacteria promotes their persistence in the airway. Upon infection, these pathogens induce host immunometabolic reprogramming, resulting in an airway milieu replete with immune-signaling metabolites. These metabolites are often toxic to the bacteria and create a steep selection pressure for the emergence of bacterial isolates adapted for long-term survival in the inflamed lung. In this review, we discuss the main differences in the host immunometabolic response to P. aeruginosa and S. aureus, as well as how these pathogens alter their own metabolism to adapt to airway metabolites and cause persistent lung infections.


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