(P)Ppgpp Synthetase Rsh Participates in the Rifampicin Tolerance of Persister Cells in Brucella Abortus in Vitro DOI
Xiaofang Liu, Pingping Wang, Yong Shi

et al.

Published: Jan. 1, 2023

Brucella abortus is a facultative intracellular pathogen that can cause chronic persistent infections resulting in abortion and infertility food animals. Recurrent be one of the results persister cells transiently display phenotypic tolerance to high dose antibiotic treatments. We examined formation B. strain A19 stationary phase investigated potential role for (p)ppGpp synthetase Rsh this process. found produce higher levels multi-drug tolerant vitro under (20 × MIC) exposure than do exponential cells. Persister cell was also induced with environmental stressors pH 4.5, phosphate buffer(pH7), 2 % NaCl 25°C, upon ampicillin, enrofloxacin rifampicin. were not formed following 1 mM H2O2. The numbers significantly increased uptake by RAW264.7 cultured macrophages. Environmental rsh expression mRNA level. null mutants (ΔRsh) fewer did complemented (CΔRsh) wildtype (WT) strains at concentrations rifampicin vitro. These data first time demonstrate phase. necessary presence On basis, new understanding recurrent advanced, thus provided basis revelation pathogenic mechanism infection Brucella.

Language: Английский

Bacterial persisters: molecular mechanisms and therapeutic development DOI Creative Commons
Hongxia Niu, Jiaying Gu, Ying Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 17, 2024

Abstract Persisters refer to genetically drug susceptible quiescent (non-growing or slow growing) bacteria that survive in stress environments such as antibiotic exposure, acidic and starvation conditions. These cells can regrow after removal remain the same stress. are underlying problems of treating chronic persistent infections relapse treatment, resistance development, biofilm infections, pose significant challenges for effective treatments. Understanding characteristics exact mechanisms persister formation, especially key molecules affect formation survival persisters is critical more treatment infections. Currently, genes related being discovered confirmed, but by which form very complex, there still many unanswered questions. This article comprehensively summarizes historical background bacterial persisters, details their complex relationship with tolerant resistant bacteria, systematically elucidates interplay between various biological processes cells, well consolidates diverse anti-persister compounds We hope provide theoretical in-depth research on suggest new ideas choosing strategies

Language: Английский

Citations

63

Improved RNA stability estimation through Bayesian modeling reveals most Salmonella transcripts have subminute half-lives DOI Creative Commons
Laura Jenniches, Charlotte Michaux, Linda Popella

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(14)

Published: March 25, 2024

RNA decay is a crucial mechanism for regulating gene expression in response to environmental stresses. In bacteria, RNA-binding proteins (RBPs) are known be involved posttranscriptional regulation, but their global impact on half-lives has not been extensively studied. To shed light the role of major RBPs ProQ and CspC/E maintaining stability, we performed sequencing Salmonella enterica over time course following treatment with transcription initiation inhibitor rifampicin (RIF-seq) presence absence these RBPs. We developed hierarchical Bayesian model that corrects confounding factors stability assays enables us identify differentially decaying transcripts transcriptome-wide. Our analysis revealed median half-life early stationary phase less than 1 min, third previous estimates. found half 500 most long-lived bound by at least one RBP, suggesting general shaping transcriptome. Integrating differential estimates cross-linking immunoprecipitation followed (CLIP-seq) approximately 30% binding sites more 40% coding or 3′ untranslated regions respective RBP. Analysis destabilized identified oxidative stress response. findings provide insights into regulation CspC/E, importance expression.

Language: Английский

Citations

16

FinO/ProQ-family proteins: an evolutionary perspective DOI Open Access

Zhen Liao,

Alexandre Smirnov

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(3)

Published: Feb. 14, 2023

RNA-binding proteins are key actors of post-transcriptional networks. Almost exclusively studied in the light their interactions with RNA ligands and associated functional events, they still poorly understood as evolutionary units. In this review, we discuss FinO/ProQ family bacterial chaperones, how evolve spread across populations what properties opportunities provide to host cells. We reflect on major conserved divergent themes within family, trying understand same ancestral fold, augmented additional structural elements, could yield either highly specialised or, contrary, globally acting regulatory hubs a pervasive impact gene expression. also consider dominant convergent trends that shaped chaperone activity recurrently implicated FinO/ProQ-like DNA metabolism, translation virulence. Finally, offer new perspective which FinO/ProQ-family regulators emerge active players both negative positive roles, significantly impacting modes trajectories hosts.

Language: Английский

Citations

10

The (p)ppGpp synthetase Rsh promotes rifampicin tolerant persister cell formation in Brucella abortus by regulating the type II toxin-antitoxin module mbcTA DOI Creative Commons
Xiaofang Liu, Pingping Wang,

Nanbo Yuan

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: May 22, 2024

Persister cells are transiently tolerant to antibiotics and associated with recalcitrant chronic infections due recolonization of host after antibiotic removal. Brucella spp. facultative pathogens that establish intracellular infection cycles in which results persistent infections. abortus forms multi-drug persister promoted by the (p)ppGpp synthetase Rsh during rifampicin exposure. Here, we confirmed formation B. stationary phase treated enrofloxacin. Deletion gene for decreased level presence these drugs different growth phases. However, deletion strain varied phases other antibiotics. also was involved treatment under certain stress conditions, including acidic exposure PBS, heat stress. Moreover, impacted cell levels or enrofloxacin RAW264.7 macrophages. Certain typeIItoxin-antitoxin modules were upregulated various conditions . We established positively regulated type II toxin-antitoxin mbcTA rifampicin-tolerant elevated ATP when promoter overexpressed background phase. Our plays a key role persistence may serve as potent novel target combination development new therapeutic approaches prevention strategies treat

Language: Английский

Citations

4

ProQ prevents mRNA degradation through inhibition of poly(A) polymerase DOI Creative Commons
S. Bergman,

Christopher Birk,

Erik Holmqvist

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(5)

Published: Feb. 27, 2025

The RNA-binding protein ProQ interacts with many transcripts in the bacterial cell. binding is associated increased messenger RNA (mRNA) levels, but a mechanistic explanation for this effect has been lacking. In Salmonella Typhimurium, affects key traits infection, including motility and intracellular survival. However, direct links between activity these phenotypes are not well understood. Here, we demonstrate that promotes biofilm formation, another virulence-associated phenotype. This strictly dependent on sigma factor RpoS. increases both RpoS rpoS mRNA neither transcription nor translation. target, expression of 3'UTR alone strongly ProQ. becomes independent strains lacking poly(A) polymerase I (PAPI), indicating protects against 3' end-dependent decay. Indeed, purified inhibits PAPI-mediated polyadenylation at ends. Finally, PAPI required ProQ's genes involved biofilm, motility, osmotic stress, virulence, inhibition general function

Language: Английский

Citations

0

Disruption of sulfur transferase complex increases bacterial intramacrophage persistence DOI Creative Commons

Huang Tang,

Zuoqiang Wang,

Congcong Li

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(5), P. e1013136 - e1013136

Published: May 14, 2025

Bacterial persisters contribute significantly to clinical treatment failure and relapse. These cells could resist antibiotic via transient phenotypic gene expression alterations. We conducted a high-throughput screening of Salmonella Typhimurium transposon mutants identify key genes for intramacrophage persistence. The results show that sulfur transferase complex encoded by yheM , yheL, yheN trmU yhhP are involved in bacterial persist macrophages downregulating the during exposure high concentrations antibiotics, even persistent infection mouse model. Mechanistically, deletion increases reactive nitrogen species (RNS) exponential phase, which inhibits respiration ATP generation. In contrast, absence promotes persister formation elevating (p)ppGpp levels stationary phase. Taken together, our data demonstrate bacteria use coordinate replication persistence adaptation various environmental stresses. findings reveal role provide promising target antibacterial therapy.

Language: Английский

Citations

0

Decoding Bacterial Persistence: Mechanisms and Strategies for Effective Eradication DOI
Abhiroop Sett, Vineet Dubey, Somok Bhowmik

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(8), P. 2525 - 2539

Published: June 28, 2024

The ability of pathogenic bacteria to evade antibiotic treatment is an intricate and multifaceted phenomenon. Over the years, failure among patients due determinants antimicrobial resistance (AMR) has been focal point for research development new therapeutic agents. However, survival by persisting under stress largely overlooked. Bacterial persisters are a subpopulation sensitive bacterial cells exhibiting noninheritable drug-tolerant phenotype. They linked recalcitrance infections in healthcare settings, turn giving rise AMR variants. importance persistence recurring firmly recognized. Fundamental work over past decade highlighted numerous unique tolerance factors contributing persister phenotype many clinically relevant pathogens. This review summarizes that could aid developing strategies against persisters.

Language: Английский

Citations

3

(P)ppGpp synthetase Rsh participates in rifampicin tolerance of persister cells in Brucella abortus in vitro DOI
Xiaofang Liu, Pingping Wang, Yong Shi

et al.

Microbial Pathogenesis, Journal Year: 2023, Volume and Issue: 183, P. 106310 - 106310

Published: Aug. 19, 2023

Language: Английский

Citations

6

The FinO/ProQ-like protein PA2582 impacts antimicrobial resistance in Pseudomonas aeruginosa DOI Creative Commons
Anastasia Cianciulli Sesso,

Armin Resch,

Isabella Moll

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: June 26, 2024

Bacteria employ small regulatory RNAs (sRNA) and/or RNA binding proteins (RBPs) to respond environmental cues. In

Language: Английский

Citations

2

The RNA Chaperone Protein ProQ is a pleiotropic regulator in enteropathogenic Escherichia coli DOI

Alexa Mihaita,

Abigail Robinson,

E. S. Costello

et al.

Microbial Pathogenesis, Journal Year: 2024, Volume and Issue: unknown, P. 107153 - 107153

Published: Nov. 1, 2024

Language: Английский

Citations

2