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New Insights into Bacterial Pathogenesis
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New Insights into Bacterial Pathogenesis

A topical collection in Pathogens (ISSN 2076-0817). This collection belongs to the section "Bacterial Pathogens".

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Editor

Dr. Carmelo Biondo

E-Mail Website
Collection Editor
Department of Human Pathology, University of Messina, 98100 Messina, Italy
Interests: host-pathogen interactions; bacterial infection; vaccines; medical mycology; innate immunity
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Bacterial infections can be more or less serious and the severity of an infection depends mainly on the type of bacterium involved. Through the activation of different strategies, pathogenic bacteria are able to adhere, enter, survive, and proliferate inside host cells. If the immune defenses are not activated in time to control the infection or if an effective antibiotic treatment is not given in time, pathogenic bacteria may cross the host’s tissue barriers, gain access to internal tissues of different parts of the body, and cause severe illness.

This Topical Collection aims to provide new insights into the link between virulence, immune escape strategies, and antibiotic resistance that different microbes adopt in the context of bacterial pathogenesis. Bacterial pathogenicity is a complex and multifactorial process and the relationship between antimicrobial resistance and virulence, which often determines the ability of bacteria to cause disease, is incompletely understood. In light of this, a fundamental objective of this Topical Collection will be to gain a better understanding of the relationship between virulence and resistance that allows pathogenic bacteria to colonize and invade human tissues. This Topical Collection welcomes high-quality contributions (original research papers and reviews) that shed light on the relationship between virulence and resistance in pathogenic bacteria.

Dr. Carmelo Biondo
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • host–microbe interaction
  • bacterial pathogenesis
  • mechanisms of immunity to bacterial infection
  • pathogen invasion
  • virulence and resistance.

Published Papers (12 papers)

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2023

Jump to: 2022, 2021

12 pages, 2882 KiB  
Article
Leptospira interrogans Serovar Icterohaemorrhagiae Failed to Establish Distinct Infection in Naïve Gilts: Lessons Learned from a Preliminary Experimental Challenge
by Romana Steinparzer, Sophie Duerlinger, Friedrich Schmoll, Adi Steinrigl, Zoltán Bagó, Denise Willixhofer, Osaid Al Salem, Sarolta Takács, Christian Knecht, René Renzhammer, Ilse Schwendenwein, Andrea Ladinig and Christine Unterweger
Pathogens 2023, 12(1), 135; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010135 - 13 Jan 2023
Viewed by 1459
Abstract
Leptospira is a pathogen involved in fertility problems in pigs. Nevertheless, little information is available on pathogenicity, transmission, tissue tropism, and immune response. The objective of this preliminary study was to induce a diagnostically detectable infection in naïve gilts using Leptospira interrogans serovar [...] Read more.
Leptospira is a pathogen involved in fertility problems in pigs. Nevertheless, little information is available on pathogenicity, transmission, tissue tropism, and immune response. The objective of this preliminary study was to induce a diagnostically detectable infection in naïve gilts using Leptospira interrogans serovar Icterohaemorrhagiae to gain the knowledge required for designing a large-scale trial. Eight seronegative fertile gilts were divided into three groups: control (n = 2), challenge (n = 3; 10 mL of 108 leptospires/mL intravenously), and contact (n = 3). A daily clinical examination and periodic sampling of blood, urine, and vaginal swabs were performed until four weeks after infection when necropsy was undertaken. Seroconversion of infected animals was detected first by a microscopic agglutination test (MAT) between four and seven days after inoculation. No clinical signs were observed except pyrexia. Laboratory data primarily remained within reference intervals. Leptospira were undetectable in all groups by real-time PCR (sera, urine, vaginal swabs, and tissue samples) and bacterial culture (urine and tissue samples). However, histologic evidence for tubulo-interstitial nephritis could be found. Based on the study results and limitations, questions to be solved and approaches to be reconsidered are raised for the conduction of further experimental studies to understand the pathogenesis and the role of Icterohaemorrhagiae in pig health. Full article
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2 pages, 146 KiB  
Editorial
Bacterial Antibiotic Resistance: The Most Critical Pathogens
by Carmelo Biondo
Pathogens 2023, 12(1), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010116 - 10 Jan 2023
Cited by 16 | Viewed by 2062
Abstract
Antibiotics primarily act on bacterial growth by eliminating bacteria or preventing them from reproducing and spreading [...] Full article

2022

Jump to: 2023, 2021

4 pages, 181 KiB  
Editorial
New Insights into Bacterial Pathogenesis
by Carmelo Biondo
Pathogens 2023, 12(1), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010038 - 26 Dec 2022
Cited by 5 | Viewed by 1538
Abstract
Pathogenicity, or the ability of a microorganism to cause disease, depends on several factors, among which the immune status of the host and the microbial species involved in the exposure play a key role [...] Full article
13 pages, 622 KiB  
Review
Recent Advances in the Use of Molecular Methods for the Diagnosis of Bacterial Infections
by Elisabetta Gerace, Giuseppe Mancuso, Angelina Midiri, Stefano Poidomani, Sebastiana Zummo and Carmelo Biondo
Pathogens 2022, 11(6), 663; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11060663 - 08 Jun 2022
Cited by 13 | Viewed by 4648
Abstract
Infections caused by bacteria have a major impact on public health-related morbidity and mortality. Despite major advances in the prevention and treatment of bacterial infections, the latter continue to represent a significant economic and social burden worldwide. The WHO compiled a list of [...] Read more.
Infections caused by bacteria have a major impact on public health-related morbidity and mortality. Despite major advances in the prevention and treatment of bacterial infections, the latter continue to represent a significant economic and social burden worldwide. The WHO compiled a list of six highly virulent multidrug-resistant bacteria named ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) responsible for life-threatening diseases. Taken together with Clostridioides difficile, Escherichia coli, Campylobacter spp., (C. jejuni and C. coli), Legionella spp., Salmonella spp., and Neisseria gonorrhoeae, all of these microorganisms are the leading causes of nosocomial infections. The rapid and accurate detection of these pathogens is not only important for the early initiation of appropriate antibiotic therapy, but also for resolving outbreaks and minimizing subsequent antimicrobial resistance. The need for ever-improving molecular diagnostic techniques is also of fundamental importance for improving epidemiological surveillance of bacterial infections. In this review, we aim to discuss the recent advances on the use of molecular techniques based on genomic and proteomic approaches for the diagnosis of bacterial infections. The advantages and limitations of each of the techniques considered are also discussed. Full article
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2021

Jump to: 2023, 2022

10 pages, 1407 KiB  
Article
Invasiveness of Escherichia coli Is Associated with an IncFII Plasmid
by Lars Johannes Krall, Sabrina Klein, Sébastien Boutin, Chia Ching Wu, Aline Sähr, Megan L. Stanifer, Steeve Boulant, Klaus Heeg, Dennis Nurjadi and Dagmar Hildebrand
Pathogens 2021, 10(12), 1645; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10121645 - 20 Dec 2021
Cited by 3 | Viewed by 4066
Abstract
Escherichia coli is one of the most prevalent pathogens, causing a variety of infections including bloodstream infections. At the same time, it can be found as a commensal, being part of the intestinal microflora. While it is widely accepted that pathogenic strains can [...] Read more.
Escherichia coli is one of the most prevalent pathogens, causing a variety of infections including bloodstream infections. At the same time, it can be found as a commensal, being part of the intestinal microflora. While it is widely accepted that pathogenic strains can evolve from colonizing E. coli strains, the evolutionary route facilitating the commensal-to-pathogen transition is complex and remains not fully understood. Identification of the underlying mechanisms and genetic changes remains challenging. To investigate the factors involved in the transition from intestinal commensal to invasive E. coli causing bloodstream infections, we compared E. coli isolated from blood culture to isolates from the rectal flora of the same individuals by whole genome sequencing to identify clonally related strains and potentially relevant virulence factors. in vitro invasion assays using a Caco- 2 cell intestinal epithelial barrier model and a gut organoid model were performed to compare clonally related E. coli. The experiments revealed a correlation between the presence of an IncFII plasmid carrying hha and the degree of invasiveness. In summary, we provide evidence for the role of an IncFII plasmid in the transition of colonization to invasion in clinical E. coli isolates. Full article
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18 pages, 3839 KiB  
Article
Secreted MbovP0145 Promotes IL-8 Expression through Its Interactive β-Actin and MAPK Activation and Contributes to Neutrophil Migration
by Doukun Lu, Hui Zhang, Yiqiu Zhang, Gang Zhao, Farhan Anwar Khan, Yingyu Chen, Changmin Hu, Liguo Yang, Huanchun Chen and Aizhen Guo
Pathogens 2021, 10(12), 1628; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10121628 - 15 Dec 2021
Cited by 6 | Viewed by 2777
Abstract
Mycoplasma bovis (M. bovis) is an important pathogen of cattle responsible for huge economic losses in the dairy and beef industries worldwide. The proteins secreted by M. bovis are mainly related to its adhesion, invasion, virulence, and intracellular survival and play [...] Read more.
Mycoplasma bovis (M. bovis) is an important pathogen of cattle responsible for huge economic losses in the dairy and beef industries worldwide. The proteins secreted by M. bovis are mainly related to its adhesion, invasion, virulence, and intracellular survival and play a role in mycoplasma–host interactions. In our previous study, we found MbovP0145, a secreted protein present in the M. bovis secretome, but little is known about its function. In this study, we assessed the inflammatory characteristics and underlined mechanism of this inflammation of recombinant MbovP0145 (rMbovP0145). For this, bovine lung epithelial cells (EBL) were stimulated by rMbovP0145 to see the IL-8 production in a time- and dose-dependent manner. We observed that rMbovP0145 increased the production of IL-8 via ERK1/2 and P38 pathway activation. Further, the effect of the M. bovis ΔMbov_0145 mutant and its complementary strain on IL-8 mRNA expression was also confirmed. A pulldown assay of the GST-tagged MbovP0145 protein with mass spectrometry demonstrated that β-actin could specifically interact with rMbovP0145 to mediate the IL-8 signaling. As knockdown of β-actin expression with RNA interference in EBL cells decreased the mRNA expression of IL-8 and the phosphorylated ERK1/2 and P38 proteins, whereas disrupted actin polymerization by cytochalasin D led to a significantly higher IL-8 expression and MAPK phosphorylation in rMbovP0145-stimulated cells. Compared to M. bovis HB0801 and its complementary strain, the culture supernatant of EBL cells infected with the M. bovis ΔMbov_0145 mutant induced less neutrophil migration to the lower chamber in a transwell system. In conclusion, MbovP0145 promoted IL-8 expression by interacting with β-actin through activation of the MAPK pathway, thus contributing to neutrophil migration. Full article
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14 pages, 2436 KiB  
Article
Roles of OmpA in Type III Secretion System-Mediated Virulence of Enterohemorrhagic Escherichia coli
by Hidetada Hirakawa, Kazutomo Suzue, Ayako Takita and Haruyoshi Tomita
Pathogens 2021, 10(11), 1496; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111496 - 17 Nov 2021
Cited by 6 | Viewed by 1950
Abstract
Outer membrane proteins are commonly produced by gram-negative bacteria, and they have diverse functions. A subgroup of proteins, which includes OmpA, OmpW and OmpX, is often involved in bacterial pathogenesis. Here we show that OmpA, rather than OmpW or OmpX, contributes to the [...] Read more.
Outer membrane proteins are commonly produced by gram-negative bacteria, and they have diverse functions. A subgroup of proteins, which includes OmpA, OmpW and OmpX, is often involved in bacterial pathogenesis. Here we show that OmpA, rather than OmpW or OmpX, contributes to the virulence of enterohemorrhagic Escherichia coli (EHEC) through its type III secretion system (T3SS). Deletion of ompA decreased secretion of the T3SS proteins EspA and EspB; however, the expression level of the LEE genes that encode a set of T3SS proteins did not decrease. The ompA mutant had less abilities to form A/E lesions in host epithelial cells and lyse human red blood cells than the parent strain. Moreover, the virulence of an ompA mutant of Citrobacter rodentium (traditionally used to estimate T3SS-associated virulence in mice) was attenuated. Mice infected with the ompA mutant survived longer than those infected with the parent strain. Furthermore, mice infected with ompA developed symptoms of diarrhea more slowly than mice infected with the parent strain. Altogether, these results suggest that OmpA sustains the activity of the T3SS and is required for optimal virulence in EHEC. This work expands the roles of outer membrane proteins in bacterial pathogenesis. Full article
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14 pages, 7446 KiB  
Review
Bacterial Antibiotic Resistance: The Most Critical Pathogens
by Giuseppe Mancuso, Angelina Midiri, Elisabetta Gerace and Carmelo Biondo
Pathogens 2021, 10(10), 1310; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101310 - 12 Oct 2021
Cited by 299 | Viewed by 28968
Abstract
Antibiotics have made it possible to treat bacterial infections such as meningitis and bacteraemia that, prior to their introduction, were untreatable and consequently fatal. Unfortunately, in recent decades overuse and misuse of antibiotics as well as social and economic factors have accelerated the [...] Read more.
Antibiotics have made it possible to treat bacterial infections such as meningitis and bacteraemia that, prior to their introduction, were untreatable and consequently fatal. Unfortunately, in recent decades overuse and misuse of antibiotics as well as social and economic factors have accelerated the spread of antibiotic-resistant bacteria, making drug treatment ineffective. Currently, at least 700,000 people worldwide die each year due to antimicrobial resistance (AMR). Without new and better treatments, the World Health Organization (WHO) predicts that this number could rise to 10 million by 2050, highlighting a health concern not of secondary importance. In February 2017, in light of increasing antibiotic resistance, the WHO published a list of pathogens that includes the pathogens designated by the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) to which were given the highest “priority status” since they represent the great threat to humans. Understanding the resistance mechanisms of these bacteria is a key step in the development of new antimicrobial drugs to tackle drug-resistant bacteria. In this review, both the mode of action and the mechanisms of resistance of commonly used antimicrobials will be examined. It also discusses the current state of AMR in the most critical resistant bacteria as determined by the WHO’s global priority pathogens list. Full article
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20 pages, 1732 KiB  
Article
Zinc Deprivation as a Promising Approach for Combating Methicillin-Resistant Staphylococcus aureus: A Pilot Study
by Yomna A. Elhakim, Amal E. Ali, Alaa El-Dien M. S. Hosny and Nourtan F. Abdeltawab
Pathogens 2021, 10(10), 1228; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101228 - 23 Sep 2021
Cited by 3 | Viewed by 3115
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global health burden with an urgent need for antimicrobial agents. Studies have shown that host immune responses limit essential metals such as zinc during infection, leading to the limitation of bacterial virulence. Thus, the deprivation of [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a global health burden with an urgent need for antimicrobial agents. Studies have shown that host immune responses limit essential metals such as zinc during infection, leading to the limitation of bacterial virulence. Thus, the deprivation of zinc as an important co-factor for the activity of many S. aureus enzymes can be a potential antimicrobial approach. However, the effect of zinc deprivation on S. aureus and MRSA is not fully understood. Therefore, the current study aimed to dissect the effects of zinc deprivation on S. aureus hemolytic activity and biofilm formation through employing biochemical and genetic approaches to study the effect of zinc deprivation on S. aureus growth and virulence. Chemically defined media (CDM) with and without ZnCl2, was used to assess the effect of zinc deprivation on growth, biofilm formation, and hemolytic activity in methicillin-susceptible S. aureus (MSSA) RN6390 and MRSA N315 strains. Zinc deprivation decreased the growth of RN6390 and N315 S. aureus strains significantly by 1.5–2 folds, respectively compared to the zinc physiological range encountered by the bacteria in the human body (7–20 µM) (p < 0.05). Zinc deprivation significantly reduced biofilm formation by 1.5 folds compared to physiological levels (p < 0.05). Moreover, the hemolytic activity of RN6390 and N315 S. aureus strains was significantly decreased by 20 and 30 percent, respectively compared to physiological zinc levels (p < 0.05). Expression of biofilm-associated transcripts levels at late stage of biofilm formation (20 h) murein hydrolase activator A (cidA) and cidB were downregulated by 3 and 5 folds, respectively (p < 0.05) suggested an effect on extracellular DNA production. Expression of hemolysins-associated genes (hld, hlb, hla) was downregulated by 3, 5, and 10 folds, respectively, in absence of zinc (p < 0.001). Collectively the current study showed that zinc deprivation in vitro affected growth, biofilm formation, and hemolytic activity of S. aureus. Our in vitro findings suggested that zinc deprivation can be a potential supportive anti-biofilm formation and antihemolytic approach to contain MRSA topical infections. Full article
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15 pages, 1222 KiB  
Article
Natural Transformation as a Mechanism of Horizontal Gene Transfer in Aliarcobacter butzleri
by Marina Bonifácio, Cristiana Mateus, Ana R. Alves, Emanuel Maldonado, Ana P. Duarte, Fernanda Domingues, Mónica Oleastro and Susana Ferreira
Pathogens 2021, 10(7), 909; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070909 - 19 Jul 2021
Cited by 6 | Viewed by 2458
Abstract
Aliarcobacter butzleri is an emergent enteropathogen, showing high genetic diversity, which likely contributes to its adaptive capacity to different environments. Whether natural transformation can be a mechanism that generates genetic diversity in A. butzleri is still unknown. In the present study, we aimed [...] Read more.
Aliarcobacter butzleri is an emergent enteropathogen, showing high genetic diversity, which likely contributes to its adaptive capacity to different environments. Whether natural transformation can be a mechanism that generates genetic diversity in A. butzleri is still unknown. In the present study, we aimed to establish if A. butzleri is naturally competent for transformation and to investigate the factors influencing this process. Two different transformation procedures were tested using exogenous and isogenic DNA containing antibiotic resistance markers, and different external conditions influencing the process were evaluated. The highest number of transformable A. butzleri strains were obtained with the agar transformation method when compared to the biphasic system (65% versus 47%). A. butzleri was able to uptake isogenic chromosomal DNA at different growth phases, and the competence state was maintained from the exponential to the stationary phases. Overall, the optimal conditions for transformation with the biphasic system were the use of 1 μg of isogenic DNA and incubation at 30 °C under a microaerobic atmosphere, resulting in a transformation frequency ~8 × 10−6 transformants/CFU. We also observed that A. butzleri favored the transformation with the genetic material of its own strain/species, with the DNA incorporation process occurring promptly after the addition of genomic material. In addition, we observed that A. butzleri strains could exchange genetic material in co-culture assays. The presence of homologs of well-known genes involved in the competence in the A. butzleri genome corroborates the natural competence of this species. In conclusion, our results show that A. butzleri is a naturally transformable species, suggesting that horizontal gene transfer mediated by natural transformation is one of the processes contributing to its genetic diversity. In addition, natural transformation can be used as a tool for genetic studies of this species. Full article
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18 pages, 3343 KiB  
Article
Prediction of Selected Biosynthetic Pathways for the Lipopolysaccharide Components in Porphyromonas gingivalis
by Wieslaw Swietnicki and Ron Caspi
Pathogens 2021, 10(3), 374; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030374 - 20 Mar 2021
Cited by 2 | Viewed by 2149
Abstract
Porphyromonas gingivalis is an oral human pathogen. The bacterium destroys dental tissue and is a serious health problem worldwide. Experimental data and bioinformatic analysis revealed that the pathogen produces three types of lipopolysaccharides (LPS): normal (O-type), anionic (A-type), and capsular (K-type). The enzymes [...] Read more.
Porphyromonas gingivalis is an oral human pathogen. The bacterium destroys dental tissue and is a serious health problem worldwide. Experimental data and bioinformatic analysis revealed that the pathogen produces three types of lipopolysaccharides (LPS): normal (O-type), anionic (A-type), and capsular (K-type). The enzymes involved in the production of all three types of lipopolysaccharide have been largely identified for the first two and partially for the third type. In the current work, we use bioinformatics tools to predict biosynthetic pathways for the production of the normal (O-type) lipopolysaccharide in the W50 strain Porphyromonas gingivalis and compare the pathway with other putative pathways in fully sequenced and completed genomes of other pathogenic strains. Selected enzymes from the pathway have been modeled and putative structures are presented. The pathway for the A-type antigen could not be predicted at this time due to two mutually exclusive structures proposed in the literature. The pathway for K-type antigen biosynthesis could not be predicted either due to the lack of structural data for the antigen. However, pathways for the synthesis of lipid A, its core components, and the O-type antigen ligase reaction have been proposed based on a combination of experimental data and bioinformatic analyses. The predicted pathways are compared with known pathways in other systems and discussed. It is the first report in the literature showing, in detail, predicted pathways for the synthesis of selected LPS components for the model W50 strain of P. gingivalis. Full article
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21 pages, 3522 KiB  
Review
Zur: Zinc-Sensing Transcriptional Regulator in a Diverse Set of Bacterial Species
by Divya Kandari, Hemant Joshi and Rakesh Bhatnagar
Pathogens 2021, 10(3), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10030344 - 15 Mar 2021
Cited by 12 | Viewed by 3509
Abstract
Zinc (Zn) is the quintessential d block metal, needed for survival in all living organisms. While Zn is an essential element, its excess is deleterious, therefore, maintenance of its intracellular concentrations is needed for survival. The living organisms, during the course of evolution, [...] Read more.
Zinc (Zn) is the quintessential d block metal, needed for survival in all living organisms. While Zn is an essential element, its excess is deleterious, therefore, maintenance of its intracellular concentrations is needed for survival. The living organisms, during the course of evolution, developed proteins that can track the limitation or excess of necessary metal ions, thus providing survival benefits under variable environmental conditions. Zinc uptake regulator (Zur) is a regulatory transcriptional factor of the FUR superfamily of proteins, abundant among the bacterial species and known for its intracellular Zn sensing ability. In this study, we highlight the roles played by Zur in maintaining the Zn levels in various bacterial species as well as the fact that in recent years Zur has emerged not only as a Zn homeostatic regulator but also as a protein involved directly or indirectly in virulence of some pathogens. This functional aspect of Zur could be exploited in the ventures for the identification of newer antimicrobial targets. Despite extensive research on Zur, the insights into its overall regulon and its moonlighting functions in various pathogens yet remain to be explored. Here in this review, we aim to summarise the disparate functional aspects of Zur proteins present in various bacterial species. Full article
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