Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity DOI Creative Commons
Yaqin Yuan, Wen Ning, Junjie Chen

et al.

mSystems, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

ABSTRACT Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant Brucella strains have been isolated worldwide without detectable mutations known antibiotic resistance genes. Here, this study identified the deletion serine/threonine protein kinase (STPK) gene B. melitensis as efficient trigger for rifampicin using bioinformatics predictions, transposon mutant library, mutation strains. Notably, absence STPK could increase expression ribosomal proteins genes involved sulfur metabolism reduced glutathione, decrease NADPH oxidase activity NADP + /NADPH ratio, which is associated with antioxidant capacity . Moreover, co-immunoprecipitation revealed that efficiently interact RpsD, possibly altering translation riboswitch expression. These findings demonstrate mediates by regulating to counteract reactive oxygen species induced rifampicin. Furthermore, approaches developed provide platform screening new spp., or its pathway can serve potential target drug development against spp. IMPORTANCE New via predictions whole-genome mechanisms , function interaction proteins.

Language: Английский

Type I toxin-antitoxin systems in bacteria: from regulation to biological functions DOI
Selene F. H. Shore, Florian H. Leinberger, Elizabeth M. Fozo

et al.

EcoSal Plus, Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

ABSTRACT Toxin-antitoxin systems are ubiquitous in the prokaryotic world and widely distributed among chromosomes mobile genetic elements. Several different toxin-antitoxin system types exist, but what they all have common is that toxin activity prevented by cognate antitoxin. In type I systems, production controlled an RNA antitoxin structural features inherent to messenger RNA. Most toxins small membrane proteins display a variety of cellular effects. While originally discovered as modules stabilize plasmids, chromosomal may also prophages, or serve important functions upon certain stress conditions contribute population-wide survival strategies. Here, we will describe intricate RNA-based regulation discuss their potential biological functions.

Language: Английский

Citations

4
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
(P)ppGpp synthetase Rel facilitates cellulose formation of biofilm by regulating glycosyltransferase in Brucella abortus DOI

Xiao Fang Liu,

Pingping Wang, Zheng Dong

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140022 - 140022

Published: Jan. 1, 2025

Language: Английский

Citations

0
What Is the Impact of Antibiotic Resistance Determinants on the Bacterial Death Rate? DOI Creative Commons

Bruno T. S. Luz,

João S. Rebelo, Francisca Monteiro

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(2), P. 201 - 201

Published: Feb. 14, 2025

Objectives: Antibiotic-resistant bacteria are widespread, with resistance arising from chromosomal mutations and genes located in the chromosome or mobile genetic elements. While determinants often reduce bacterial growth rates, their influence on death under bactericidal antibiotics remains poorly understood. When exposed to which they susceptible, typically undergo a two-phase decline: fast initial exponentially decaying phase, followed by persistent slow-decaying phase. This study examined how affect rates during both phases. Methods: We analyzed of ampicillin-exposed Escherichia coli populations strains sensitive ampicillin but resistant nalidixic acid, rifampicin, both, carrying conjugative plasmids RN3 R702. Results: Single mutants acid rifampicin decayed faster than cells early whereas double-resistant mutant exhibited prolonged survival. These contrasting impacts suggest epistatic interactions between mutations. Persistent-phase for did not differ significantly wild-type cells. In contrast, plasmid-carrying displayed distinct dynamics: R702 plasmid-bearing showed higher persistent-phase plasmid-free cells, while lower rates. Conclusions: Bactericidal may kill other more effectively Moreover, epistasis occur when different same cell, impacting potential antibiotic choice. results have significant implications optimizing eradication protocols clinical settings, as well animal health industrial food safety management.

Language: Английский

Citations

0
Unlocking the enigma of phenotypic drug tolerance: Mechanisms and emerging therapeutic strategies DOI
Alok Mishra, Ritesh Thakare,

Bela G. Santani

et al.

Biochimie, Journal Year: 2023, Volume and Issue: 220, P. 67 - 83

Published: Dec. 31, 2023

Language: Английский

Citations

3
Serine/threonine protein kinase mediates rifampicin resistance in Brucella melitensis through interacting with ribosomal protein RpsD and affecting antioxidant capacity DOI Creative Commons
Yaqin Yuan, Wen Ning, Junjie Chen

et al.

mSystems, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

ABSTRACT Brucellosis, a zoonotic disease, has re-emerged in both humans and animals, causing significant economic losses globally. Recently, an increasing number of rifampicin-resistant Brucella strains have been isolated worldwide without detectable mutations known antibiotic resistance genes. Here, this study identified the deletion serine/threonine protein kinase (STPK) gene B. melitensis as efficient trigger for rifampicin using bioinformatics predictions, transposon mutant library, mutation strains. Notably, absence STPK could increase expression ribosomal proteins genes involved sulfur metabolism reduced glutathione, decrease NADPH oxidase activity NADP + /NADPH ratio, which is associated with antioxidant capacity . Moreover, co-immunoprecipitation revealed that efficiently interact RpsD, possibly altering translation riboswitch expression. These findings demonstrate mediates by regulating to counteract reactive oxygen species induced rifampicin. Furthermore, approaches developed provide platform screening new spp., or its pathway can serve potential target drug development against spp. IMPORTANCE New via predictions whole-genome mechanisms , function interaction proteins.

Language: Английский

Citations

0