Bacterial nucleoid-associated protein HU as an extracellular player in host-pathogen interaction

Stojková, Pavla; Špidlová, Petra

doi:10.3389/fcimb.2022.999737

Cited by 6 publications

(3 citation statements)

References 62 publications

(100 reference statements)

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“…NAPs form numerous aggregated structures with bacterial genomic DNA and participate in processes such as replication, separation, translation, and repair of prokaryotic genomic DNA. Among the primary NAPs studied are histone‐like protein (HU), leucine-responsive regulatory protein (Lrp), virulence factor transcriptional regulator (Mga Spn ) and Histone-like nucleoid-structuring (H-NS) ( Casadesús and Low, 2006 ; Xiao et al., 2021 ; Ziegler and Freddolino, 2021 ; Ramamurthy et al., 2022 ; Stojkova and Spidlova, 2022 ).…”

Section: What Is Epigenetics?mentioning

confidence: 99%

Antimicrobial resistance and mechanisms of epigenetic regulation

Wang

2023

Front. Cell. Infect. Microbiol.

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The rampant use of antibiotics in animal husbandry, farming and clinical disease treatment has led to a significant issue with pathogen resistance worldwide over the past decades. The classical mechanisms of resistance typically investigate antimicrobial resistance resulting from natural resistance, mutation, gene transfer and other processes. However, the emergence and development of bacterial resistance cannot be fully explained from a genetic and biochemical standpoint. Evolution necessitates phenotypic variation, selection, and inheritance. There are indications that epigenetic modifications also play a role in antimicrobial resistance. This review will specifically focus on the effects of DNA modification, histone modification, rRNA methylation and the regulation of non-coding RNAs expression on antimicrobial resistance. In particular, we highlight critical work that how DNA methyltransferases and non-coding RNAs act as transcriptional regulators that allow bacteria to rapidly adapt to environmental changes and control their gene expressions to resist antibiotic stress. Additionally, it will delve into how Nucleolar-associated proteins in bacteria perform histone functions akin to eukaryotes. Epigenetics, a non-classical regulatory mechanism of bacterial resistance, may offer new avenues for antibiotic target selection and the development of novel antibiotics.

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Section: What Is Epigenetics?mentioning

confidence: 99%

Antimicrobial resistance and mechanisms of epigenetic regulation

Wang

2023

Front. Cell. Infect. Microbiol.

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“…In vivo HU homologs affect gene expression and change the distribution of RNA polymerase by altering DNA topology within promoter regions or promoting long-range DNA contacts (11, 12). Recent studies have revealed that HU homologs influence transcription of genes connected to stress response or virulence in many bacterial species including: E. coli ( 13, 14 ) Salmonella enterica (15), Vibrio parahaemolyticus ( 16 ), Francisella tularensis (17) and Helicobacter pylori (18).…”

Section: Introductionmentioning

confidence: 99%

The role of two major nucleoid associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

Strzałka,

Mikołajczyk,

Kowalska

et al. 2024

Preprint

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Streptomycesare sporulating soil bacteria with enormous potential for secondary metabolites biosynthesis. Regulatory networks governingStreptomyces coelicolordifferentiation and secondary metabolites production are complex and composed of numerous regulatory proteins ranging from specific transcriptional regulators to sigma factors. Nucleoid associated proteins (NAPs) are also believed to contribute to regulation of gene expression. Upon DNA binding these proteins impact DNA accessibility. Among NAPs HU proteins are the most widespread and abundant. Unlike other bacteria, theStreptomycesgenome encodes two HU homologs: HupA and HupS, differing in structure and expression profile. In this study, we explore whether HupA and HupS affectS. coelicolorgrowth under optimal and stressful conditions and how they control global gene expression. By testing both single and double mutants we address the question of both HU homologs complementarity. The lack of bothhupgenes led to growth and sporulation inhibition, as well as increased spore fragility. Our data indicate a synergy between the functions of HupA and HupS duringS. coelicolorgrowth. We also demonstrate, that both HU homologs can be considered global transcription regulators influencing expression of numerous genes encoding proteins linked to chromosome topology, secondary metabolites production and transcription. We identify the independent HupA and HupS regulons as well as genes under the control of both HupA and HupS proteins. Our data indicate some extent of redundancy as well as independent function of both homologs.ImportanceStreptomycesbelong to the bacterial family widely used in the production of antibiotics as well as research for new bioactive substances with antimicrobial properties. Gene expression inStreptomyces, and consequently the production of secondary metabolites, is controlled by a vast and complex network of transcriptional regulators. Our data indicate that two proteins, HupA and HupS, involved in the maintenance of chromosome structure, also participate in this regulatory network. Their presence appears to important forS. coelicolor’s adaptation for survival in unfavorable conditions such as high temperature. The lack of one or both HU proteins affects the expression of many genes, indicating that they act as global transcriptional regulators.

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“…They are primarily DNA structuring proteins, but their functioning as transcription factors also has been shown [ 26 ]. Apart from its intracellular role, secretion of the HU protein and its extracellular role also have been studied [ 27 ]. HU protein exists as both homo- [ 28 ] and hetero-dimer [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Arginine 58 is indispensable for proper function of the Francisella tularensis subsp. holarctica FSC200 HU protein, and its substitution alters virulence and mediates immunity against wild-type strain

Pavlik

Špidlová

2022

Virulence

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HU protein, a member of the nucleoid-associated group of proteins, is an important transcription factor in bacteria, including in the dangerous human pathogen Francisella tularensis . Generally, HU protein acts as a DNA sequence non-specific binding protein and it is responsible for winding of the DNA chain that leads to the separation of transcription units. Here, we identified potential HU protein binding sites using the ChIP-seq method and two possible binding motifs in F. tularensis subsp. holarctica FSC200 depending upon growth conditions. We also confirmed that FSC200 HU protein is able to introduce negative supercoiling of DNA in the presence of topoisomerase I. Next, we showed interaction of the HU protein with a DNA region upstream of the pigR gene and inside the clpB gene, suggesting possible regulation of PigR and ClpB expression. Moreover, we showed that arginine 58 and partially arginine 61 are important for HU protein’s DNA binding capacity, negative supercoiling induction by HU, and the length and winding of FSC200 chromosomal DNA. Finally, in order to verify biological function of the HU protein, we demonstrated that mutations in arginine 58, arginine 61, and serine 74 of the HU protein decrease virulence of FSC200 both in vitro and in vivo and that immunization using these mutant strains is able to protect as many as 100% of mice against wild-type challenge. Taken together, our findings deepen knowledge about the role of the HU protein in tularaemia pathogenesis and suggest that HU protein should be addressed in the context of tularaemia vaccine development.

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Bacterial nucleoid-associated protein HU as an extracellular player in host-pathogen interaction

Cited by 6 publications

References 62 publications

Antimicrobial resistance and mechanisms of epigenetic regulation

Antimicrobial resistance and mechanisms of epigenetic regulation

The role of two major nucleoid associated proteins in Streptomyces, HupA and HupS, in stress survival and gene expression regulation

Arginine 58 is indispensable for proper function of the Francisella tularensis subsp. holarctica FSC200 HU protein, and its substitution alters virulence and mediates immunity against wild-type strain

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