Brucellosis: epidemiology, pathogenesis, diagnosis and treatment–a comprehensive review

Qureshi, Kamal A.; Parvez, Adil; Fahmy, Nada A.; Abdel Hady, Bassant H.; Kumar, Shweta; Ganguly, Anusmita; Atiya, Akhtar; Elhassan, Gamal O.; Alfadly, Saeed O.; Parkkila, Seppo; Aspatwar, Ashok

doi:10.1080/07853890.2023.2295398

Cited by 35 publications

(4 citation statements)

References 159 publications

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“…Our data indicate that Rsh promotes persister cell formation by a mechanism that may involve rifampicin and enrofloxacin in B. abortus . Significantly, rifampicin commonly is used to treat brucellosis ( Qureshi et al, 2023 ). We speculate that Rsh may be a novel therapeutic target in combination with rifampicin for clearing persister cells in chronic Brucella infections.…”

Section: Discussionmentioning

confidence: 99%

“…Brucella establishes an intracellular infection cycle in macrophages to achieve intracellular proliferation. Brucella is widespread in more than 170 countries and is transmitted indirectly to humans through inhalation of airborne agents or directly by interaction with infected animals or contaminated animal products or as an occupational hazard ( Qureshi et al, 2023 ). Human brucellosis is one of the world’s dominant pervasive zoonotic diseases ( Guo et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although vaccine strains including Brucella abortus A19, B. melitensis M5, B. abortus S19 and B. suis S2, are used commonly to prevent and control brucellosis in livestock ( He et al, 2022 ), these vaccines possess residual virulence which increases persistence and causes infectious risk in animals and humans during vaccination ( He et al, 2022 ). The choice of antibiotic for treatment of human brucellosis is restricted ( Ficht, 2003 ), although doxycycline and rifampicin are used most frequently ( Qureshi et al, 2023 ). In addition, intricate contacts between bacteria and host may establish chronic infection and long-term survival in hosts in certain situations ( He et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…First, the bacteria may evade host immune responses to achieve long-lasting infection. Second, the emergence of antimicrobial resistance in Brucella allows the pathogen to survive treatment ( Qureshi et al, 2023 ). Third, bacteria may evade killing from usually lethal doses of antibiotic by entering a physiologically dormant state referred to as persistence ( Maisonneuve and Gerdes, 2014 ; Mode et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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The (p)ppGpp synthetase Rsh promotes rifampicin tolerant persister cell formation in Brucella abortus by regulating the type II toxin-antitoxin module mbcTA

Liu,

Wang,

Yuan

et al. 2024

Front. Microbiol.

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

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%