Antibiotic-recalcitrant infections, defined as the prolonged carriage of pathogenic bacteria even in the presence of antibiotics, are often caused by bacteria that are genetically susceptible to the drug. These recalcitrant bacteria fail to proliferate in the presence of antibiotics but remain viable such that they may recolonize their niche following antibiotic withdrawal. Significant progress has been made in our understanding of antibiotic-recalcitrant Salmonella, which are thought to be the source of infection relapse. In recent years, it has been shown that recalcitrant bacteria manipulate host immune defences and could directly contribute to the spread of antimicrobial resistance. In this Review, we provide an overview of what is currently known about the antibiotic recalcitrance of Salmonella during infection and highlight knowledge gaps requiring additional research in the future.
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Antibiotic-recalcitrant Salmonella during infection.
Nat Rev Microbiol
November 2024
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Antibiotic-recalcitrant infections, defined as the prolonged carriage of pathogenic bacteria even in the presence of antibiotics, are often caused by bacteria that are genetically susceptible to the drug. These recalcitrant bacteria fail to proliferate in the presence of antibiotics but remain viable such that they may recolonize their niche following antibiotic withdrawal. Significant progress has been made in our understanding of antibiotic-recalcitrant Salmonella, which are thought to be the source of infection relapse.
View Article and Find Full Text PDFHost stress drives tolerance and persistence: The bane of anti-microbial therapeutics.
Cell Host Microbe
June 2024
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. Electronic address:
Antibiotic resistance, typically associated with genetic changes within a bacterial population, is a frequent contributor to antibiotic treatment failures. Antibiotic persistence and tolerance, which we collectively term recalcitrance, represent transient phenotypic changes in the bacterial population that prolong survival in the presence of typically lethal concentrations of antibiotics. Antibiotic recalcitrance is challenging to detect and investigate-traditionally studied under in vitro conditions, our understanding during infection and its contribution to antibiotic failure is limited.
View Article and Find Full Text PDFStudying antibiotic persistence in vivo using the model organism Salmonella Typhimurium.
Curr Opin Microbiol
December 2022
Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland. Electronic address:
Antibiotic persistence permits a subpopulation of susceptible bacteria to survive lethal concentrations of bactericidal antibiotics. This prolongs antibiotic therapy, promotes the evolution of antibiotic-resistant pathogen strains and can select for pathogen virulence within infected hosts. Here, we review the literature exploring antibiotic persistence in vivo, and describe the consequences of recalcitrant subpopulations, with a focus on studies using the model pathogen Salmonella Typhimurium.
View Article and Find Full Text PDFA natural product from Streptomyces targets PhoP and exerts antivirulence action against Salmonella enterica.
J Antimicrob Chemother
October 2022
Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina.
Background: The overprescription and misuse of classical antimicrobial compounds to treat gastrointestinal or systemic salmonellosis have been accelerating the surge of antibiotic-recalcitrant bacterial populations, posing a major public health challenge. Therefore, alternative therapeutic approaches to treat Salmonella infections are urgently required.
Objectives: To identify and characterize actinobacterial secreted compounds with inhibitory properties against the Salmonella enterica PhoP/PhoQ signal transduction system, crucial for virulence regulation.
The vulnerable versatility of Salmonella antibiotic persisters during infection.
Cell Host Microbe
December 2021
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, UK; Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address:
Tolerance and persistence are superficially similar phenomena by which bacteria survive bactericidal antibiotics. It is assumed that the same physiology underlies survival of individual tolerant and persistent bacteria. However, by comparing tolerance and persistence during Salmonella Typhimurium infection, we reveal that these two phenomena are underpinned by different bacterial physiologies.
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