The HigB/HigA toxin/antitoxin system of <i>Pseudomonas aeruginosa</i> influences the virulence factors pyochelin, pyocyanin, and biofilm formation

Wood, Thomas K.; Wood, Thomas K.

doi:10.1002/mbo3.346

Cited by 88 publications

(130 citation statements)

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“…GraT inhibits ribosome biogenesis by directly interacting with DnaK (a known facilitator of late stage ribosome biogenesis) or by attacking an unknown target (Ainelo et al, ). Although the exact targets of the endonuclease activity of HigB in PAO1 remain to be elucidated, an in vitro cleavage assay using ompA and ompF mRNAs as substrates in P. aeruginosa PA14 showed that HigB exhibits mRNase activities (Wood and Wood, ) and HigB reduces the intracellular c‐di‐GMP level by affecting c‐di‐GMP metabolism genes (Zhang et al, ). In addition, using a DNA microarray study and a PA14 transposon mutant ( MAR2×T7 transposon insertion), the activation of HigB due to transposon insertion in higA was found to reduce the expression of pyochelin and pyochelin‐related genes in PA14 (Wood and Wood, ).…”

Section: Discussionmentioning

confidence: 99%

“…Among these strains, highly conserved higBA loci are not only found in Pseudomonas aeruginosa but are also present in 26 other Pseudomonas strains, such as P. syringae, P. putida and P. fluorescens (53%-86% identity for higA and 63%-86% identity for higB). Among the identified loci, the recently characterized PA14_RS25265 and Rorf_67641 genes in P. aeruginosa PA14 (Li et al, 2016;Wood and Wood, 2016) are the same as HigB/HigA in PAO1. The GraTA TA system in P. putida KT2440 has been identified as a novel temperature-dependent TA pair (Tamman et al, 2014), and the antitoxin GraA has 56% identity with HigA in PAO1, whereas GraT has 70% identity with HigB in PAO1 (Fig.…”

Section: Gene Idmentioning

confidence: 99%

“…Due to the high toxicity caused by overexpressing the toxins, to probe the physiological role of toxins, many TA systems have been studied using the deletion of the entire TA operon or by deletion of the antitoxin gene and the resulting phenotypes of these mutants have been attributed to the toxin of the system. For example, recent studies using the higA :: MAR2×T7 transposon insertion mutant obtained from the P. aeruginosa PA14 transposon mutant library showed that induction of HigB due to the absence of functional HigA reduces the production of the virulence factors and biofilm formation (Wood and Wood, ), and the activation of HigB due to the absence of functional HigA increases type III secretion system‐mediated cytotoxicity (Li et al, ). When applying a genome‐scale method to identify genes required by Yersinia pestis in the production of bubonic plague, one antitoxin‐coding gene hicB3 (first named ympt1.66c ) was found to be important for full virulence (Pradel et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Antitoxin HigA inhibits virulence gene mvfR expression in Pseudomonas aeruginosa

Guo

Sun

et al. 2019

Environmental Microbiology

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Summary Toxin/antitoxin (TA) systems are ubiquitous in bacteria and archaea and participate in biofilm formation and stress responses. The higBA locus of the opportunistic pathogen Pseudomonas aeruginosa encodes a type II TA system. Previous work found that the higBA operon is cotranscribed and that HigB toxin regulates biofilm formation and virulence expression. In this study, we demonstrate that HigA antitoxin is produced at a higher level than HigB and that higA mRNA is expressed separately from a promoter inside higB during the late stationary phase. Critically, HigA represses the expression of mvfR, which is an important virulence‐related regulator, by binding to a conserved HigA palindrome (5′‐TTAAC GTTAA‐3′) in the mvfR promoter, and the binding of HigB to HigA derepresses this process. During the late stationary phase, excess HigA represses the expression of mvfR and higBA. However, in the presence of aminoglycoside antibiotics where Lon protease is activated, the degradation of HigA by Lon increases P. aeruginosa virulence by simultaneously derepressing mvfR and higB transcription. Therefore, this study reveals that the antitoxin of the P. aeruginosa TA system is integrated into the key virulence regulatory network of the host and functions as a transcriptional repressor to control the production of virulence factors.

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Section: Discussionmentioning

confidence: 99%

Section: Gene Idmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antitoxin HigA inhibits virulence gene mvfR expression in Pseudomonas aeruginosa

Guo

Sun

et al. 2019

Environmental Microbiology

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“…A comprehensive suite of virulence genes was determined by utilising the Pseudomonas Genome Database (http://www.pseudomonas.com/) [195]. For the HigB toxins, primer sequences were obtained and blasted to identify the gene product [116]. For a gene to be considered present searching required 100% of the gene to be present in the BLAST output.…”

Section: Microbiological Methodsmentioning

confidence: 99%

“…In 2016 Wood et al also described a type two toxin/anti-toxin system in P. aeruginosa consisting of the proteins HigB and HigA. The role of this system is to regulate bacterial toxicity [116].…”

Section: Update On P Aeruginosa Blood Stream Infectionmentioning

confidence: 99%

Pseudomonas aeruginosa blood stream infections: clinical and molecular epidemiology, virulence and outcome

McCarthy¹

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IntroductionPseudomonas aeruginosa is a virulent pathogen. It can exist both in the environment and the human host. Recent work by Turner et al suggests that it is the environment that P. aeruginosa exists that determines the virulence factors that are expressed [1]. P. aeruginosa bloodstream infections (BSI) are predominantly seen in the hospital or healthcareassociated host [2][3][4][5]. This BSI is no longer the rare entity of the original case series in the 1950's, with increasing prevalence over the subsequent decades [6,7]. The associated morbidity and mortality with this infection is considerable [2,[8][9][10]. This has not improved over time [7].The antibiotic treatment options available, in the current age of global antibiotic resistance, has not kept pace. A mortality benefit of combination antibiotic therapy in the setting of P. aeruginosa BSI has not been consistently shown [11][12][13][14][15][16][17]. In the settings of drug resistance or the immunocompromised host, more effective ways to utilise current antibiotic therapy must be considered.It is therefore timely that we further characterise the clinical and molecular epidemiology, virulence genotype and outcome of P. aeruginosa BSI. MethodsBSI episode data was collected retrospectively over a three-year time period from the first of January 2008 to the first of January 2011. This involved seven tertiary care institutions, servicing an urban population of 2.24 million. Extensive epidemiological, clinical, laboratory, treatment and outcome data was collected as per a pre-formulated data collection sheet (Appendix A). For purposes of the study on BSI in the setting of febrile neutropenia, data was collected from a single institution over an extended period of time from the 1 st of January 2006 to the 1 st of April 2014.Ethics approval was obtained from each of the study sites.A P. aeruginosa BSI isolate collection was also collated for study. This involved five public and private laboratories. Isolates were collected from the time period of the first of January 2008 to the first of January 2013. The laboratories service eight tertiary care institutions and one secondary care institution. Permission was obtained from each of the laboratories.ii Results 595 P. aeruginosa BSI episodes were characterised from the study centres. 942 BSI isolates were collated and analysed as part of the BSI isolate collection.A retrospective cohort study of monomicrobial P. aeruginosa BSI described the recent Australian epidemiology of this BSI. The longitudinal mortality of this infection was found to increase with time and at one year was greater than would be expected for the comparative death rate predicted by the median Charlson's co-morbidity index (CCI) of the cohort [18].Detailed description of a retrospective cohort of community acquired (CAI) P. aeruginosa BSI gave new insight into the epidemiology of this group of patients. Multivariate analysis comparing CAI and health-care associated infection cohorts (HCAI) found that CAI is not associated with a shorter len...

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Phylogenomic analysis of Citrobacter sp. strain AAK_AS5 and its metabolic capabilities to support nitrogen removal behavior

et al. 2022

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Despite the ubiquity of the genus Citrobacter in clinical, industrial, and environmental scenarios, a large number of Citrobacter strains have not been explored at the genome‐scale level. In this study, accurate taxonomic assignment of strain AAK_AS5 isolated from activated sludge was achieved by in‐silico genomic comparison using Overall Genome‐based Relatedness Indices (ANI(OAT): 97.55%, ANIb:97.28%, and ANIm: 97.83%) that indicated its closest identity to the related strain Citrobacter portucalensis A60T. Results were consistent with a digital DNA–DNA hybridization value of 80% with C. portucalensis A60T which was greater than the species boundary value >70% for delineating closely related bacterial species. Gene mining through Kyoto Encyclopedia of Genes and Genomes (KEGG), and annotation using rapid annotation subsystem technology (RAST) revealed the notable gene contents for nitrogen metabolism and other pathways associated with nitrate/nitrite ammonification (28 genes), ammonia assimilation (22 genes), and denitrification pathways (14 genes). Furthermore, the strain AAK_AS5 also exhibited a high soluble chemical oxygen demand (sCOD), NH4+‐N, and NO3‐‐N removal efficiency of 91.4%, 90%, and 93.6%, respectively thus validating its genetic capability for utilizing both (NH4)2SO4 and KNO3 as the nitrogen source. The study provided deeper insights into the phylogenomics and the genetic potential of Citrobacter, sp. strain AAK AS5 associated with nitrogen metabolism thus signifying the potential application of the isolate for treating nitrogen‐rich wastewaters.

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The HigB/HigA toxin/antitoxin system of Pseudomonas aeruginosa influences the virulence factors pyochelin, pyocyanin, and biofilm formation

Cited by 88 publications

References 72 publications

Antitoxin HigA inhibits virulence gene mvfR expression in Pseudomonas aeruginosa

Antitoxin HigA inhibits virulence gene mvfR expression in Pseudomonas aeruginosa

Pseudomonas aeruginosa blood stream infections: clinical and molecular epidemiology, virulence and outcome

Phylogenomic analysis of Citrobacter sp. strain AAK_AS5 and its metabolic capabilities to support nitrogen removal behavior

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